PHILIPPINE NATIONAL FORMULARY

MANUAL FOR PRIMARY CARE PROVIDERS

9th Edition

Department of Health
Manila, Philippines

2021
 DISCLAIMER
This Manual which is intended for the Primary Care prescribers contains the list
of medicines, their therapeutic information, and other data that were collated as
meticulously as possible through the collaborative efforts of the editorial team and the
Interim Guidelines Core Committee, medical specialists, specialty societies, and
pharmacists applying the standard clinical practice current at the time of the
undertaking. Thus, the contents are the most recent only insofar as the dates of the
actual collaboration are concerned. There is no guarantee that after the final drafting
for this edition, the new information that may subsequently become available will be
included.

While diligent effort has been made to ensure the accuracy of the information
for each medicine included in this volume, the data presented here is a synopsis of
key points taken from the full Philippine National Formulary Manual (2019). The
complete labeling contains additional precautionary information that may be of
significance in specific cases. Thus, the editors do not warrant that the information
contained herein is in every aspect accurate.

The editors have included only the information that they consider to be essential,
relevant, and useful for the prescribers at the Primary Care level. The editors hope that
this Manual will be a readily accessible, easily understandable, updated source of
independent medicine information for these prescribers. Nevertheless, readers should
refer to more recent and comprehensive materials and publications to supplement
this Manual.

Moreover, the recommendations incorporated into the clinical practice

guidelines are intended to serve only as guides that will supplement and not replace
the best clinical judgment of the prescribing clinicians. Readers are enjoined to
confirm the information contained herein with other sources, particularly with regard
to the newest or the latest information.

All rights reserved 2021

Any part of the book or its entirety may be reproduced or transmitted without any
alteration, in any form or by any means, with permission from DOH provided it is
not used for commercial purposes.
PHILIPPINE NATIONAL FORMULARY
MANUAL FOR PRIMARY CARE PROVIDERS
9th Edition

DEPARTMENT OF HEALTH

FRANCISCO T. DUQUE III, MD, MSc

Secretary of Health
GERARDO V. BAYUGO, MD, MPH, CESO I
Undersecretary, Health Regulation Team

ATTY. CHARADE B. MERCADO-GRANDE

Assistant Secretary, Health Regulation Team

ANNA MELISSA S. GUERRERO, MD, MPH (HTA)

Chief, Pharmaceutical Division
 EDITORIAL TEAM

Marita B. Dantes, MD, FPNA

Editor-in-Chief

Joyce Anne dP. Ceria-Pereña, RPh, MPM

Kate D. Dunlao, RPh
Mica Anna B. Policarpio, RPh
Johanna B. Mallari, RPh, MPH
Tanya Paula S. Samson, RN
Members of the Editorial Team

John Michael L. Roque

Lorenzo P. Javier, RPh
John Alvin T. Morales
Technical Assistants

MEDICAL MONOGRAPHS CORE COMMITTEE

Johanna B. Mallari, RPh, MPH

Mica Ann B. Policarpio, RPh
Kate D. Dunlao, RPh
Tanya Paula S. Samson, RN

INTERIM GUIDELINES CORE COMMITTEE

Marita B. Dantes, MD, FPNA

Joyce Anne dP. Ceria- Pereña, RPh, MPM
Mica Anna B. Policarpio, RPh
Kate D. Dunlao, RPh
 CONTRIBUTORS

Diabetes Philippines
Dr. Maria Marci Cruz
Dr. Grace delos Santos

DOH- Disease Prevention and Control Bureau

Dr. Carmela Granada

DOH- National Tuberculosis Program

Dr. Celina Garfin
Dr. Mary Rosary Santiago

Pediatric Infectious Disease Society of the Philippines

Dr. Carmina A. De Los Reyes
Dr. Kristine Alvarado-De La Cruz
Dr. Jay Ron O. Padua
Dr. Maria Theresa T. Policarpio

Philippine Academy of Pediatric Pulmonologists

Dr. Cristan Q. Cabanilla
Dr. Regina Canonizado
Dr. Nerissa De Leon

Philippine College of Chest Physicians

Dr. Eileen Aniceto
Dr. Rodolfo Pagcatipunan

Philippine Dermatological Society

Dr. Camille B. Angeles
Dr. Mary Charmaine G. Castillo
Dr. Ma. Purita G. Paz- Lao
Dr. Francisco D. Rivera IV

Philippine Heart Association

Dr. Ronald Cuyco
Dr. Ryan Buendia
Dr. Nanette Rey
 Philippine Health Insurance Corporation
Dr. Joy Maala

Philippine Society of Endocrinology and Metabolism

Dr. Michael Villa

Philppine Society of Hypertension

Dr. Albert Atilano
 Department of Health – Health Regulation Team

MESSAGE

Rational use of medicines is one of the pillars of the Philippine Medicines Policy. The
Philippine National Formulary (PNF) serves as an essential tool to promote rational
selection and use of essential medicines in the country. It has been seven years since
the 8th edition of the PNF Manual for Primary Healthcare (PHC) facilities has been
launched and it is only timely to provide our primary care facilities with an up-to-date
reference to guide rational selection and use of medicines in the community setting,
aligned with the mandate of the Universal Health Care Law. For this reason, the
Department of Health, through the Pharmaceutical Division (PD), updated and revised
the content of the PNF Manual for PHC and renamed it to “PNF Manual for Primary
Care Providers” to emphasize that it is intended to be optimally utilized by healthcare
professionals providing first line of care in the communities.

The 9th edition of the PNF Manual for Primary Care Providers provides an updated list
of essential medicines, drug information for primary care facilities as well as the
current guidelines/clinical pathways on diseases commonly encountered in the
primary care setting. On behalf of the DOH Health Regulation Team, I would like to
commend and congratulate the editorial team and everyone who devoted their time
and effort in the successful completion of this publication and in advocating for rational
prescribing, dispensing, and use of medicine to achieve optimal health outcomes for
all Filipino patients.

Congratulations and mabuhay!

GERARDO V. BAYUGO, MD, MPH, CESO I

Undersecretary of Health
Health Regulation Team
 PREFACE TO THE 2ND VOLUME
Welcome to the 2nd volume of the Philippine National Formulary Manual for Primary
Care Providers. The 1st volume that was published and distributed in 2014 had been
envisioned to equip the municipal and city health officers with a more sufficient list of
essential medicines, updated and readily accessible prescriber information, and the
most current evidence-based clinical practice guidelines.

Our basic principles remain to be two-fold: first, to guide the primary care physicians
that will assure the use of cost-effective and safe medicines while practicing
adherence to the tenets of the rational use of medicines; and secondly, to provide a
manual that will be relevant and responsive to the needs of the communities.

Advancement in the science of medicine continues to add more basic and clinical
knowledge and experience that may lead to changes in the paradigms and guidelines.
Thus, the need for an updated volume of this manual arose. Moreover, the new edition
of the PNF was released in 2019 to which alignment of the manual became necessary.
Changes in policies, particularly those of Philhealth and the UHC, became important
considerations also.

Changes in this 2nd volume include the following: the addition of essential medicines
such as the antihypertensive combination pills, otic and ophthalmic medicines, pain
relievers, medicines for the emergency management of patients awaiting transfer to
the hospitals, and those administered at health units with Basic Emergency Obstetric
and Newborn Care (BEmONC) and Mental Health Medicines Access Program (MHMAP)
Access Sites; updates in the interim clinical guidelines of commonly encountered
diseases at the primary care level; updates in the recommended vaccination
schedules; the incorporation of practice essentials in dermatology and guidelines for
the management of common bacterial skin infections; and, the addition of practical
guidance in the use of common Philippine medicinal plants. Rational prescribing of
medicines and the current and emerging antimicrobial resistance were once more
highlighted. There was also renewed emphasis on the promotion of health and
prevention of diseases.

We are privileged to have prepared this manual and hope that this can be a practical
and valuable resource for you. We also continue to enjoin everyone to constantly keep
in mind the rational use of medicines.

THE EDITORIAL TEAM

 ACKNOWLEDGMENTS

We acknowledge, with sincere thanks, the invaluable contribution of the following in

the finalization of the Philippine National Formulary Manual for Primary Care Providers:

All the experts from the national health programs (NHP), and professional medical
societies for participating in the review of the content of the Formulary as well as in the
updating of the practice essentials and interim guidelines.

Dr. Clemencia Bondoc, National President of the Association of Municipal Health

Officers of the Philippines, and the following Doctors to the Barrios (DTTB): Dr.
Alphonse Raphael Guevarra (Linapacan, Palawan), Dr. Camelle Mae Celis (Pilar, Cebu),
Dr. Krizzia Rae Jabonillo (Lila, Bohol), Dr. Dena Mae Amor Desabille (Santa Fe, Cebu),
Dr. Nina Lao (Bantayan, Cebu), and Dr. Dawn Pauline Bituin (Mabinay, Negros Oriental
), for generously participating in the consultative meetings to provide comments on the
list of primary care medicines as well as on the practice essentials and guidelines.

Dr. Myrna Mendoza of the Philippine Society of Microbiology and Infectious Diseases
for providing the Philippine Clinical Practice Guidelines on the Management of Urinary
Tract Infections and the management guidelines on Leptospirosis.

Dr. Isidro Sia and Rainier Galang who reviewed and provided information for the Guide
on the Philippine Medicinal Plants for the Primary Care Providers and Joseph Alvin
Buenaflor for providing original photos of the medicinal plants.
 TABLE OF CONTENTS

GENERAL GUIDE i
GENERAL GUIDE ON THE USE OF THIS MANUAL i
MEDICINE MONOGRAPH KEY iv
GENERAL GUIDE TO PRESCRIBING vii
A. RATIONAL APPROACH TO THERAPEUTICS vii
B. VARIATION IN DOSE-RESPONSE ix
1. Medicine Formulation ix
2. Body Weight and Age ix
3. Dose Calculation in Children x
4. Physiologic and Pharmacokinetic Variables xi
5. Medicine Distribution xii
6. Medicine Metabolism and Excretion xii
7. Pharmacodynamic Variables xiii
8. Disease
Variable xiii.
Environmental Variables xiii
C. ADHERENCE TO, COMPLIANCE WITH AND MAINTENANCE
OF MEDICINE TREATMENT xiii
1. Patient-Related Reasons xiv
2. Disease-Related Reasons xiv
3. Doctor-Related Reasons xiv
4. Doctor-Patient Interaction xiv
5. Prescription-Related Reasons xv
6. Pharmacist-Related Reasons xv
7. Recommendations to the Prescribers xv
D. ADVERSE EFFECTS AND INTERACTIONS xvi
1. ADVERSE DRUG REACTIONS (ADR) xvi
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS xvi
a Extremes of Age xvi
b. Intercurrent Illnesses and Co-Morbidities xvi
c. Medicine Interactions xvi
d. Incompatibilities between Medicines and Fluids xvii
e. Adverse Effects Caused by Traditional Medicines xvii
f. Effect of Food on Medicine Absorption xvii
E. PRESCRIPTION WRITING xvii
1. PRESCRIPTION FORM xvii
2. INCORRECT PRESCRIPTIONS xviii
3. NARCOTICS AND CONTROLLED SUBSTANCES xix
F. PATIENT COUNSELING xx
1. WHAT TO COUNSEL xx
2. WHO AND WHEN TO COUNSEL xx
 3. COUNSELING: PROCESS STEPS xxi

ANTIMICROBIAL RESISTANCE xxiii

RELEVANT LAWS, REGULATIONS AND POLICIES xxxix

MEDICINE AND THERAPEUTIC INFORMATION

US FDA PREGNANCY RISK CATEGORIES 1
SYMBOLS AND ABBREVIATIONS 2
MEASUREMENTS 4
DRUGS AND CYP ENZYMES 5

ALIMENTARY TRACT AND METABOLISM 10

A. Drugs for Acid-Related Disorders: 10
• Aluminum hydroxide + Magnesium Hydroxide 10
• Omeprazole 11
• Amoxicillin 13
• Clarithromycin 13
• Metronidazole 14
B. Drugs for Functional Gastrointestinal Disorders: 14
• Atropine 14
• Dicycloverine 16
• Hyoscine (as N-Butylbromide) 17
C. Anti-Emetics and Anti-Nauseants: 18
• Metoclopramide 18
D. Drugs for Constipation: 20
• Bisacodyl 20
• Lactulose 21
E. Anti-Diarrheals, Intestinal Anti-inflammatory/ Anti-Infective Agents: 22
• Oral rehydration Salts (ORS 75 - Replacement) 22
F. Antipropulsives: 24
• Loperamide 24
G. Drugs Used in Diabetics: 25
• Biphasic Isophane Human Insulin 70/30 27
• Isophane Human Insulin/ NPH Insulin 28
• Regular Insulin 29
• Metformin 29
• Gliclazide 31
H. Vitamins: 32
• Multivitamins 32
• Retinol (Vitamin A) 33
• Ascorbic Acid (Vitramin C) 35
• Folic Acid 36
• Phytomenadione (Vitamin K) 37
• Vitamin B1 B6 B12 38
I. Mineral Supplements: 38
• Calcium carbonate 39
• Calcium gluconate 41
 • Calcium Carbonate + Cholecalciferol (Vitamin D3) 42
• Ferrous Salt 43
• Ferrous Salt + Folic Acid 44
• Potassium chloride 46
• Zinc 47
• Micronutrient Powder 48

BLOOD AND BLOOD FORMING ORGANS 49

A. Antithrombotic Agents: 49
• Aspirin 49
• Clopidogrel 50
B. Antihemorrhagics: 52
• Tranexamic Acid 52
C. Anti-Anemic Preparations: 54
• Ferrous Salt 54
• Ferrous Salt + Folic Acid 55
• Folic Acid 56
D. Intravenous Solutions and Intravenous Solution Additives: 56
• Dextrose in Sodium Chloride 56
• 5% Dextrose in 0.9% Sodium Chloride 56
• 5% Dextrose in Lactated Ringer’s 57
• Balanced Multiple Maintenance Solution 59
• Balanced Multiple Replacement Solution 60
• 0.9% Soium Chloride 61
• 5% Dextrose in Water 62
• Glucose 63
• Lactated Ringer's Solution 65
• Magnesium Sulfate 66
• Sodium Chloride (IV) 67
• Sterile water for Injection 68

CARDIOVASCULAR SYSTEM 70
A. Cardiac Therapy: 70
• Digoxin 70
• Dopamine 71
• Epinephrine 73
• Isosorbide Dinitrate 75
• Isosorbide-5-Mononitrate 76
B. Antihypertensives: 78
• Hydralazine 78
• Captopril 80
• Enalapril 82
• Enalapril + Hydrochlorothiazide 83
• Losartan 85
• Losartan + Hydrochlorothiazide 86
• Metoprolol 90
• Atenolol 91
• Amlodipine 92
• Nicardipine 93
 • Diltiazem 96
• Clonidine 97
• Methyldopa 99
D. Diuretics: 100
• Hydrochlorothiazide 100
• Furosemide 101
E. Lipid Modifying Agents: 103
• Atorvastatin 103
• Rosuvastatin 105
• Simvastatin 106
• Fenofibrate 108
F. Antithrombotic Agents: 109
• Aspirin 109
• Clopidogrel 110

DERMATOLOGICALS 111
A. Antifungals for Dermatological Use: 111
• Clotrimazole 111
• Ketoconazole 111
B. Antipruritic for Topical Use: 112
• Calamine, plain 112
C. Antibiotics and Chemotherapeutics for Dermatological Use: 113
• Fusidate sodium (Fusidic Acid) 113
• Mupirocin 113
• Silver sulfadiazine 114
D. Corticosteroids for Dermatological Use: 116
• Hydrocortisone 116
E. Antiseptics and Disinfectants: 117
• Povidone-Iodine 117
• Alcohol, ethyl 118
• Hydrogen peroxide 119

GENITOURINARY SYSTEM AND SEX HORMONES 120

A. Uterotonics: 120
• Magnesium sulfate 120
B. Sex Hormone and Modulators of the Genital System: 124
• Ethinylestradiol + Levonorgestrel 124
• Medroxyprogesterone 125
C. Urologicals: 127
• Tamsulosin 127
• Finasteride 127

SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES

AND INSULINS 129
A. Glucocorticoids: 129
• Dexamethasone 130
• Hydrocortisone 131
• Methylprednisolone 133
• Prednisone 135
 B. Oxytocic: 137
• Oxytocin 137
C. Thyroid and Anti-Thyroid Preparations: 138
• Levothyroxine 138
• Methimazole 141

ANTI-INFECTIVES (SYSTEMIC) 143

A. Antibacterials: 143
Amphenicols: 146
• Chloramphenicol 146
Tetracyclines: 147
• Doxycycline 147
Penicillins: 150
• Amoxicillin 150
• Ampicillin 152
• Penicillin G Benzathine (Benzathine benzylpenicillin) 154
• Penicillin G Crystalline 157
• Phenoxymethylpenicillin 158
Beta Lactamase Resistant Penicillins: 160
• Cloxacillin 160
• Oxacillin 162
Penicillin + Beta Lactamase in Combination: 163
• Co-Amoxiclav (Amoxicillin + Clavulanate) 163
Cephalosporins: 166
• Cefalexin 166
• Cefixime 167
• Ceftriaxone 169
• Cefuroxime 173
Sulfonamide and Trimethoprim: 175
• Cotrimoxazole 175
Macrolides: 177
• Azithromycin 177
• Clarithromycin 179
• Erythromycin 181
Lincosamide: 183
• Clindamycin 183
Aminoglycoside: 185
• Gentamicin 185
Fluoroquinolones: 187
• Ciprofloxacin 187
Imidazole derivative: 190
• Metronidazole 190
Nitrofuran derivative: 191
• Nitrofuranton 191
B. Antifungals: 193
• Clotrimazole 193
C. Anti-Tuberculosis: 194
• Ethambutol 194
• Isoniazid 195
• Pyrazinamide 196
 • Rifampicin 197
• Isoniazid + Rifampicin 199
• Isoniazid + Rifampicin + Ethambutol 199
• Isoniazid + Rifampicin + Pyrazinamide + Ethambutol 200
D. Anti-Leprosy: 200
• Clofazimine 200
• Dapsone 201
• Rifampicin 202
E. Anti-Virals: 203
• Aciclovir/ Acyclovir 203
• Oseltamivir 204
F. Immune Sera and Immunoglobulins: 206
• Anti-Rabies Serum 206
• Anti-Tetanus Serum 207
• Cobra Antivenin 207
• Rabies Immunoglobulin 209
• Tetanus Immunoglobulin 211
G. Vaccines: 212
• BCG Vaccine 212
• Diphtheria-Tetanus Toxoid and Pertussis Vaccine 213
• Haemophilus influenzae Type B Conjugate Vaccine (Hib) 215
• Hepatitis B Vaccine (Recombinant DNA) 216
• Influenza Polyvalent Vaccine 217
• Live Attenuated Measles Vaccine 219
• Live Attenuated Measles, Mumps and Rubella Vaccine 220
• Meningococcal Polysaccharide vaccine 222
• Poliomyelitis Vaccine (Types 1,2,3) Inactivated 223
• Live Attenuated Bivalent Oral Polio Vaccine (Types 1 and 3) 225
• Rabies Vaccine 227
• Tetanus Toxoid 229
• Typhoid Vaccine

MUSCULOSKELETAL SYSTEM 234

A. Anti-Inflammatory and Antirheumatic Products: 234
• Aspirin 234
• Celecoxib 235
• Ibuprofen 238
• Mefenamic Acid 239
• Naproxen 241

NERVOUS SYSTEM 244

A. Analgesics: 244
• Tramadol 244
• Ibuprofen 245
• Paracetamol 247
B. Antiepileptics: 249
• Carbamazepine 249
• Valproic Acid/ Valproate 251
• Diazepam 253
 C. For Eclampsia: 255
• Magnesium Sulfate 255
D. Anti-Parkinson Drugs: 256
• Biperiden 256
• Levodopa + Carbidopa 258
• Diphenhydramine 260
E. Local Anesthetics: 260
• Lidocaine 260
F. Drugs for Neuropathic Pains: 262
• Carbamazepine 262
• Gabapentin 262
G. Psycholeptics: 264
Antipsychotic Medicines: 264
• Chlorpromazine 264
• Clozapine 266
• Fluphenazine 270
• Haloperidol 272
• Lithium Carbonate 275
• Olanzapine 277
• Risperidone 279
Anxiolytic: 282
• Diazepam 282
Other Psycholeptic Drugs: 283
• Carbamazepine 283
• Valproic Acid/Valproate 285
• Escitalopram 288
• Fluoxetine 289
• Sertraline 291
H. Anti-vertigo Drugs 293
• Betahistine 293

ANTIPARASITICS, INSECTICIDES AND REPELLANTS 295

A. Antiprotozoals: 295
Agents against Amebiasis and other protozoal agents: 295
• Metronidazole 295
Anti-Malarials: 296
• Artemether + Lumefantrine 296
• Chloroquine 298
• Primaquine 300
Other Anti-Malarials: 301
• Doxycycline 301
B. Antihelmintics: 302
• Praziquantrel 302
• Albendazole 303
• Diethylcarbamazine 304
• Mebendazole 304
C. Ectoparasiticides, including Scabecides: 305
• Permethrin 305
RESPIRATORY SYSTEM 307
A. Throat Preparations: 307
• Povidone-Iodine Oral Antiseptic 307
B. Drugs for Obstructive Airway Diseases: 307
• Epinephrine (Adrenaline) 307
• Fluticasone + Salmeterol 308
• Ipratropium 310
• Ipratropium + Salbutamol 311
• Montelukast 313
• Salbutamol 314
C. Cough and Cold Preparations: 316
• Butamirate 316
D. Antihistamines: 316
• Cetirizine 316
• Diphenhydramine 318
• Loratadine 319
• Hydrocortisone 320
E. Herbal Preparations for Cough and Cold: 316
• Lagundi 322

SENSORY ORGANS 323

A. Ophthalmic Antibacterial Preparation: 323
• Erythromycin eye ointment 323
• Tobramycin eye drops 323
• Tobramycin + Dexamethasone eye drops 324
B. Antibacterial Otic Preparation: 325
• Clotrimazole otic solution 325
• Neomycin + Polymixin B + Fluocinolone Acetonide ear drop 325
• Ofloxacin 326
C. Anesthetics (Topical): 327
• Lidocaine Topical Spray 327

VARIOUS MEDICINES/ ALL OTHER THERAPEUTIC PRODUCTS 329

A. General Antidotes: 329
• Activated Charcoal 329
• Alcohol, ethyl 330
• Atropine 331
• Phytomenadione (Phytonaione, Vitamin K1 ) 333

INTERIM PRACTICE GUIDELINES 334

A. INTERIM PRACTICE GUIDELINES USER GUIDE 335
B. INFECTIOUS DISEASES 337
• COMMUNITY ACQUIRED PNEUMONIA IN IMMUNOCOMPETENT
ADULTS 340
• PEDIATRIC COMMUNITY ACQUIRED PNEUMONIA 351
• URINARY TRACT INFECTION 365
• PRACTICE ESSENTIALS IN DERMATOLOGY AND COMMON BACTERIAL SKIN
INFECTIONS IN ADULTS 397
 • ANTIBIOTICS FOR INFECTIOUS DIARRHEA 421

C. NONCOMMUNICABLE DISEASES 431

• HYPERTENSION IN ADULTS 434
• DIABETES MELLITUS 454
• COMMON POISONING 488
Caustics: Acids 488
Caustics: Alkali – Sodium Hypochlorite 492
Kerosene 495
N-Methyl Carbamates 498
Organochlorine 499
Organophosphates 502
Watusi (Dangerous Firecrackers) 507
Ethanol 509
Cobra Bite 516
Paralytic Shellfish Poisoning 519

VACCINATION SCHEDULES 523

GUIDE FOR THE USE OF COMMON PHILIPPINE MEDICINAL PLANTS

FOR PRIMARY CARE PROVIDERS 526

DIRECTORY 554

REFERENCES 556

INDEX 566
GENERAL GUIDE
 GENERAL GUIDE ON THE USE OF THIS MANUAL

The Philippine National Formulary Manual for Primary Care Level allows primary
healthcare prescribers – physicians and dentists – to quickly find important medicine
information and practice guidelines for diseases and other health conditions
commonly encountered in the primary care setting.

In this current edition of the PNF, the essential medicines list, monographs, and
cross-reference index have been integrated into a single manual. The initial section
emphasizes the fundamental points in the rational approach to the use of medicines
and summarizes the physiologic and pharmacologic variables that affect response to
pharmacotherapeutic agents and that are necessary factors in the determination of
dosage and frequency of administration. A review of the guidelines on proper
prescription writing, adequate patient counseling, and a timely report on the emerging
problems due to Antimicrobial Resistance were included under this General Guide.

The main section contains the essential medicines for the primary care
facilities. The medicines are arranged using the Anatomical Therapeutic Chemical
(ATC) Classification System, Medicines with more than one therapeutic indication
appear in more than one category. Each monograph consists of:

• Generic Name

• Dosage Form/Strength

• Indications

• Antimicrobial Resistance Alert (for the Anti-Infectives)

• Contraindications

• Dosage (weight and/or age-specific dosage recommendations)

• Dose Adjustments (for patients with renal or hepatic disease; or the elderly
patients)

• Precautions/Warnings

• Adverse Drug Reactions

• Drug Interactions

Page | i
 • Recommendations on Proper Intake

• Pregnancy Category

Succinct explanations accompany the precautions, adverse events, and drug

interactions to emphasize the scientific bases for using the medicines. In addition,
concise guidelines on the pharmacotherapeutic management of leptospirosis, rabies,
eradication of H. pylori infection in peptic ulcer disease, and dehydration in children,
as well as general information on methicillin-resistant Staphylococcus aureus (MRSA)
and precepts in the use of antibiotics, were incorporated into the prescribing
information of the medicines primarily used to treat these diseases. General
Information regarding the classes of the medicines that reviews the most important
and salient characteristics was included to serve as a review for the physicians.

The succeeding section of this Formulary contains the Interim Practice

Guidelines that were developed by the PNF PHC Core Group, in collaboration with the
specialists from the different medical societies. These were based on the most recently
published clinical practice guidelines (CPGs) in the management of CAP, UTI in adults,
hypertension, diabetes mellitus, and common poisoning that were developed by the
relevant specialty societies as well as the clinical practice guidelines published in
international journals. These were enhanced and adapted to the current needs at the
primary healthcare facilities by the editors. A summary of the WHO guidelines for the
management of diarrheal diseases was also incorporated.

References
The general guide and the therapeutic information in this Formulary have been
adapted from various current and comprehensive references with the WHO Model
Formulary (2008) and the Philippine National Formulary 8th edition (2019) serving as
the primary materials. Notable references include the latest Philippine FDA-approved
product information and the locally published National Antibiotics Guidelines 2019.
The complete list of the sources and materials cited are found in the section on
References.

The entries were compiled, reviewed, and updated by the PNF PHC Core Group
using sound evidence-based processes. The monographs and the interim guidelines
were submitted to the specialist representatives for final review.

Page | ii
 The Interim Practice Guidelines on the management of CAP, UTI in adults,
hypertension, diabetes mellitus, common poisoning, leptospirosis, and rabies were
primarily based on the most recently published Philippine national guidelines
developed by the relevant task forces composed of members from various medical
and other specialty societies. The WHO and IMCI guidelines served as the bases for
the management of diarrheal diseases were used.

Page | iii
 MEDICINE MONOGRAPH KEY
The medicine monograph key summarizes and describes the types of
information contained in this edition that the physicians and dentists can utilize in
prescribing medicines for the patients in primary healthcare facilities. Other healthcare
professionals can also derive information regarding the rational use of medicines from
this Manual. The key also shows the format of how the prescribing information is
arranged. The information contained in this Manual has been validated against the
current locally and internationally published clinical practice guidelines available at the
time of the undertaking and the reviews made by specialty experts and the medical
and surgical specialty societies.

INTRODUCTION OF THE MEDICINE

GENERIC NAME

DOSAGE FORM/STRENGTH: (for oral or parenteral administration)

INDICATION/S: This section only includes Philippine FDA-approved indications.

Notably, the indications included in this edition are limited to the more commonly
encountered conditions at the primary care facilities. Thus, indications for conditions
requiring more specialized care or hospitalization (e.g., acute bacterial meningitis,
high-risk pneumonia) are not included. Indications that will require a referral to a higher
level of healthcare facility or specialist (e.g., diabetes in children and pregnant women)
will be written as such. In addition, the indications listed for the Anti-Infective Agents
are restricted to those included in the most current local clinical practice guidelines
that were made available to the editors and/or the latest published recommendations
of the Philippine Antimicrobial Resistance Surveillance Program.

In some of the entries in the Section on Anti-Infectives and the CPGs on Infectious
diseases, the phrase ANTIMICROBIAL RESISTANCE ALERT! appears as a warning
regarding the use of antibiotics to which pathogens have been found to have emerging
or increasing antimicrobial resistance. These alerts are based on the most recently
published report of the Philippine Antimicrobial Resistance Surveillance Program.

CONTRAINDICATION/S: This section details disease states where and patient

populations for whom the medicine should not be used.

Page | iv
DOSE: This section lists dosages of the medicines for adult, child, and elderly patients,
if specified, as indicated in the official FDA-approved labeling and/or other main
references.

DOSE ADJUSTMENT/S: This section gives dosage adjustment recommendations for

the elderly, or patients with renal or hepatic impairment.

PRECAUTIONS: This section details (1) harmful conditions related to the use of the
medicine (e.g., exacerbations, increased risk of adverse effects), and (2) disease
states or patient populations where caution is advised. This may also include
precautions for breastfeeding mothers and nursing infants. Black Box Warnings are
included.

ADVERSE DRUG REACTIONS: This section denotes side effects and adverse drug
reactions (ADRs) listed in the official FDA-approved labeling. These are enumerated
based on the occurrence or frequency (i.e., Common – ≥1%; Less Common – ≥0.1%
and <1%; and Rare ≥0.01% and <0.1%). Under the Less Common and Rare ADRs,
only those deemed significant based on the clinical judgments of the editors (e.g.,
serious, life-threatening, or potentially irreversible ADRs) are listed. For complete
prescribing information, readers are enjoined to refer to the official Philippine FDA-
approved labeling.

DRUG INTERACTION/S: This section includes the effects and implications of the
concomitant administration of different medicines, or their use together with food,
based on official Philippine FDA-approved labeling and other references. Moreover, the
included entries are categorized based on: (1) which combinations should be
monitored closely, and (2) which should be avoided.

ADMINISTRATION: This section lists recommendations on the proper intake or

administration of the medicines.

PREGNANCY CATEGORY: This section is based on the US FDA Pregnancy Risk

Categories. (Please refer to the Appendix for the complete listing and description of the
risk categories).

ATC CODE: This section is based on the Anatomical Therapeutic Chemical (ATC)
classification system, which groups the active medical substances according to the

Page | v
organ or system on which they act and according to their therapeutic, pharmacologic,
and chemical properties.

Page | vi
 GENERAL GUIDE TO PRESCRIBING
A. RATIONAL APPROACH TO THERAPEUTICS
Rational use of medicines (RUM) is the fundamental concept where patients
receive medicines, when these are needed, that are appropriate for the clinical
needs, in doses that meet the individual requirements, for an adequate period, at
the lowest possible cost, and administered correctly by the right person.
1. The problem of irrational use of medicines concerns the following:
a. This is one of the most critical causes of unsuccessful treatment
outcomes, health hazards that include antimicrobial resistance,
wastage of resources, and increased health costs.
b. Worldwide, 50% of medicines are prescribed, dispensed, or sold
inappropriately; moreover, half of the patient population fails to take
them correctly.
c. In the Philippines, many irrational practices are prevalent such as
rationing (often termed as “diby-diby”), prescribing of inappropriate
alternative medicines, “shotgun” therapy, misuse and overuse of
antibiotics, dispensing of antibiotics without a prescription, self-
medication, buying medicines piecemeal (“tingi”), and failure to
complete treatment.
d. The problems that underlie the irrational practices are far-reaching
and include an inadequate supply of medicines that are in turn due
to the sheer number of patients coming for a consultation, the lack
of funds or poor support from the government officials, poverty,
inherent limitations of the National Formulary, anomalous
transactions, geographical isolation and poor health literacy of
patients and even some health care providers.
2. The solutions for many of the causes of irrational practices are often beyond
the control of primary care physicians. However, the physicians, as stewards
of the people’s health, must lead by example the efforts to adhere faithfully
to the principles of RUM.
3. The basic tenets of RUM include:
a. Prescribing medicines only when these are necessary;
b. Prescribing appropriately; and
c. Considering the benefits of administering medicines in relation to the
risks involved.
4. The key points of the systematic processes that will assist in determining
the proper treatment are:
a. Defining the patient’s problem.
b. Specifying the therapeutic objective.
c. Selecting the therapeutic strategy.
Page | vii
 The selected strategy for achieving a health outcome should
be agreed upon with the patient. The total costs for all therapeutic
options should be considered. Strategies can either be non-
pharmacologic and/or pharmacologic.
1.) Non-pharmacologic Treatment
• This implies that patients do not always need medicine
for the treatment of their conditions.
• This includes changes in lifestyle or diet, use of
physiotherapy or exercise, provision of adequate
psychological support, and other non-pharmacologic
treatments.
• This is of equal importance as prescription medicines;
instructions for such treatments must be written,
explained, and monitored in the same way.
2.) Pharmacologic Treatment
a) Selecting the correct group of medicines:
There are two fundamental principles for rational
therapeutics:
i. Knowledge about the pathophysiology involved
in the clinical situation of each patient
ii. Pharmacodynamics of the chosen group of
medicines
b) Verifying the suitability of the chosen pharmaceutical
treatment:
i. Is the active substance chosen suitable for the
patient?
ii. Is the dosage form suitable for the patient?
iii. Is the standard dosage schedule suitable for the
patient?
iv. Is the standard duration of treatment suitable for
the patient?
c) Prescription Writing:
i. This serves as the link between the prescriber,
the pharmacist (or dispenser), and the patient.
ii. This is vital to the successful management of
presenting medical conditions (see detailed
Prescription Writing below).

Page | viii
 iii. In the Philippines, only validly registered medical
doctors and dentists (as well as veterinarians)
are allowed to prescribe.
d) Giving information, instructions, and warnings:
This is essential in ensuring patient adherence.
e) Monitoring treatment:
i. The evaluation of the follow-up and the outcome
of treatment allows for possible termination of
treatment (if the patient’s problem is solved), or
its reformulation when necessary.
ii. This step gives rise to important information
about the effects of medicines, contributing to
the pool of knowledge on pharmacovigilance;
that, in turn, is needed to promote the rational
use of medicines.
B. VARIATION IN DOSE-RESPONSE
A correct dose regimen is necessary for success in medicine treatment. The
use of standard doses in the marketing literature suggests that standard
responses are the rule, but in reality, there is considerable variation in medicine
response. The reasons for the variation include adherence (see Adherence with
Medicine Treatment), medicine formulation, body weight and age, composition,
variation in medicine absorption, distribution, metabolism, and excretion, variation
in pharmacodynamics, disease variables, and genetic and environmental
variables.
1. MEDICINE FORMULATION
a. Poorly formulated medicines may fail to disintegrate or to dissolve.
b. Enteric-coated medicines may pass through the GI tract intact.
Changes in absorption can produce sudden changes in medicine
concentrations of medicines with a narrow therapeutic-to-toxic ratio. For
such medicines, quality control surveillance should be carried out.

2. BODY WEIGHT AND AGE

Although the concept of varying the dose with the body weight or age
of children has long been a tradition, adult doses have been assumed to be
the same irrespective of size or shape. However, adult weights vary from 2-
to 3-folds. Furthermore, a patient with a large fat mass can store large
excesses of highly lipid-soluble medicines compared with a lean patient of
the same weight.
Age can also be important. Adolescents may metabolize some
medicines relatively more rapidly than adults, while the elderly may have
reduced renal function and eliminate some medicines more slowly.

Page | ix
 3. DOSE CALCULATION IN CHILDREN
Many children’s doses are standardized by weight (and therefore
require multiplying by the body weight in kilograms to determine the child’s
dose). Occasionally, the doses have been standardized by body surface
area (BSA) in m2.
To calculate a child’s medication based on BSA, use the formula:

𝑐𝑐ℎ𝑖𝑖𝑖𝑖𝑖𝑖′𝑠𝑠 𝐵𝐵𝐵𝐵𝐵𝐵
𝑥𝑥 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 = 𝑐𝑐ℎ𝑖𝑖𝑖𝑖𝑖𝑖′𝑠𝑠 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑
1.73
with the BSA computed as follows:

𝑊𝑊 × 𝐻𝐻
𝐴𝐴 = �
3600
where:
A – Patient’s BSA (m2)
W – Patient’s weight in (kg)
H – Patient’s height (cm)
3600 – Conversion/correction factor (kg/m3)
If the weight is expressed in pounds (lbs) and the height in inches (in):

𝑊𝑊 × 𝐻𝐻
𝐴𝐴 = �
3131
• Young children may require a higher dose for each kilogram than adults
because of their higher metabolic rates.
• Calculation by body weight in an overweight child may result in higher
than necessary doses being administered. In such cases, doses should
be calculated using an ideal weight, related to height and age.
• Nomograms can also be used to calculate body surface values based
on a child’s height and weight.
• Where the dose for children is not readily available, prescribers should
seek specialist advice before prescribing for a child.

Page | x
4. PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES
a. Pharmacokinetics
• This area of study deals with changes of concentration in the
drug product, or in a drug and its metabolites, in the body,
after it has been administered. This includes the time course
of drug absorption, distribution, metabolism, and elimination.
• A basic understanding of the factors which control drug
concentration at the site of action (e.g., bioavailability, area
under the curve, and half-life) is important for the optimal use
of drugs.
1.) Bioavailability
• This refers to the amount of medicine from an
administered dosage form that enters the
systemic circulation, and the rate at which it
appears in the bloodstream.
• Changes in a drug’s bioavailability may be
thought of in terms of changes in exposure to the
drug which, if substantial, can relate to safety
and efficacy concerns.
2.) Bioequivalence
• This indicates that a drug in two or more similar
dosage forms reaches the general circulation at
the same relative rate and the same relative
extent (i.e., that the plasma level profiles of the
drug obtained using the two dosage forms are
the same).
• This is an important consideration in several key
situations involving lot-to-lot consistency,
innovator to generic product therapeutic
equivalence, and situations where a marketed
product undergoes changes in certain aspects
(formulation, manufacturing process, and
dosage strength).
3.) Half-life
• This indicates the time required to reduce the
amount of medicine in the body or the plasma
concentration by 50%.
• This is a clinically useful pharmacokinetic
parameter because this indicates when the next
dose of medicine needs to be administered, and
thus helpful in determining an optimal dosing
regimen.
Page | xi
 b. Medicine absorption rates may vary widely among individuals and in
the same individual at different times and in different physiological
states.
• Medicines taken after a meal are delivered to the small
intestine more slowly than in the fasting state, leading to much
lower medicine concentrations.
• In pregnancy, gastric emptying is also delayed, while some
medicines may increase or decrease gastric emptying, and
affect the absorption of other medicines.
5. MEDICINE DISTRIBUTION
a. Fat-soluble medicines (vitamins A, D, E, and K) are stored in adipose
tissues.
b. Water-soluble medicines are distributed chiefly in the extracellular
space.
c. Acidic medicines bind strongly to plasma albumin.
d. Basic medicines go to muscle cells.
e. Hence, variations in plasma albumin concentration, fat content, or
muscle mass may all contribute to dose variation.
6. MEDICINE METABOLISM AND EXCRETION
a. Medicine metabolism is affected by genetic, environmental, and
disease-state factors.
b. Medicine acetylation shows genetic polymorphism, where individuals
fall clearly into either fast or slow acetylator types. This means that
some patients can metabolize medicines more rapidly (fast
acetylators) than others (slow acetylators).
c. Medicine oxidation, however, is polygenic.
• Although a small proportion of the population can be classified
as very slow oxidizers of some medicines, there is a normal
distribution of medicine-metabolizing capacity for most
medicines and most subjects.
d. Many medicines are eliminated by the kidneys without being
metabolized.
e. Renal disease or toxicity of some medicines on the kidney can slow
the excretion of some medicines.
f. Hepatic disease or toxicity of some medicines on the liver can slow the
excretion of some medicines.

Page | xii
 7. PHARMACODYNAMIC VARIABLES
Significant variations in receptor response to some medicines
(especially CNS responses, such as pain and sedation) are attributed to
genetic factors, tolerance, medicine interactions, and medicine
dependence.
8. DISEASE VARIABLES
a. Both liver and kidney diseases can have major effects on metabolism
and elimination, respectively (resulting in increasing toxicity), but also
through effects on plasma albumin (resulting in increasing free
medicine and thus toxicity).
b. Heart failure can also affect the metabolism of medicines with rapid
hepatic clearance (e.g., lidocaine).
c. Respiratory disease and hypothyroidism can impair the oxidation of
drugs.
9. ENVIRONMENTAL VARIABLES
a. Many medicines and environmental toxins can induce the hepatic
microsomal enzyme oxidizing system or cytochrome P450
oxygenases, leading to more rapid metabolism and elimination, and
thus less effective treatment.
b. Environmental pollutants, anesthetic medicines, and other
compounds, such as pesticides, can also induce metabolism.
c. Diet and nutritional status also affect pharmacokinetics:
1.) In malnourished infantile and elderly populations, medicine
oxidation rates are decreased.
2.) High protein diets, charcoal-cooked foods, and certain other
foods act as metabolizing enzyme inducers.
3.) Chronic alcohol use induces oxidation of some medicines; but
in the presence of high circulating alcohol concentrations,
medicine metabolism may be inhibited.
C. ADHERENCE TO, COMPLIANCE WITH, AND MAINTENANCE OF MEDICINE
TREATMENT
• One of the most important reasons for treatment failure is poor adherence
to, compliance with, and maintenance of the treatment plan.
• Reasons for the above may be related to: (1) the patient, (2) the disease,
(3) the doctor, (4) the prescription, (5) the pharmacist, or (6) the health
system.
o For instance, patients' perceptions of the risk and severity of adverse
drug reactions may differ from those of the healthcare provider and
may affect adherence.

Page | xiii
 o Poor/incorrect prescribing or a dispensing error may also create a
problem, which patients may have neither the insight nor the courage
to question.
• Valid reasons for poor compliance include the following: the medicine may
be poorly tolerated, may cause obvious adverse effects, or may be
prescribed in a toxic dose. Failure to adhere to such a prescription has been
described as “intelligent non-compliance”.
• Low-cost strategies for improving adherence increase the effectiveness of
health interventions and reduce costs. Such strategies must be tailored to
the individual patient. Healthcare providers should be familiar with
techniques for improving adherence and they should employ systems to
assess and determine what influences it.

1. PATIENT-RELATED REASONS
a. Women tend to be more adherent than men.
b. Younger patients and the very elderly tend to be less adherent.
c. People living alone are less adherent than those living with partners
or spouses.
d. Specific education interventions have been reported and shown to
improve adherence and compliance.
e. Some patient disadvantages include illiteracy, poor eyesight, or
cultural attitudes.
f. Cultural attitudes include a preference for traditional or alternative
medicines, and distrust of modern medicines.
g. Economic factors affect patient adherence, compliance, and
maintenance.
2. DISEASE-RELATED REASONS
Conditions with a known worse prognosis (e.g., cancer) or painful
conditions (e.g., rheumatoid arthritis) elicit better adherence than
asymptomatic “perceived as benign” conditions such as hypertension.
3. DOCTOR-RELATED REASONS
a. Failure to inspire confidence in the treatment offered
b. Little or no explanation provided
c. Too many medicines prescribed
d. Errors in prescribing
e. Overall attitude to the patient
4. DOCTOR-PATIENT INTERACTION
a. Quality of the doctor-patient interaction is crucial to adherence and
compliance.
Page | xiv
 b. “Satisfaction with the interview” is one of the best predictors of good
adherence.
c. If they are in doubt or dissatisfied, they may turn to alternative
options, including complementary medicine.
5. PRESCRIPTION-RELATED REASONS
a. Illegible or inaccurate prescriptions may discourage patients to
adhere to medications.
b. Lost prescriptions may delay patients to start or continue
medications.
c. Prescriptions not refilled as intended or instructed for chronic
disease may reduce maintenance.
d. Too complex prescriptions (greater number of different medicines,
poorer adherence).
e. Multiple doses decrease adherence and compliance, especially if
more than two doses per day are given.
f. Adverse effects, like drowsiness, impotence, or nausea, reduce
adherence.
6. PHARMACIST-RELATED REASONS
a. Manner and professionalism
b. Pharmacist information and counseling can serve as a valuable
reinforcement, as long as they agree with the physician’s advice.

7. RECOMMENDATIONS TO THE PRESCRIBERS

a. Review the prescription to make sure it is correct.
b. Spend time explaining the health problem and the reason for the
medicine.
c. Establish a good rapport with the patient.
d. Explore problems, such as difficulty with reading the label or getting
the prescription filled.
e. Encourage patients to bring their medication to the clinic so that
tablet counts can be done to monitor compliance.
f. Encourage patients to learn the names of their medicines, and review
their regimen with them. Write notes for them.
g. Keep treatment regimens simple.
h. Communicate with other healthcare professionals to develop a team
approach and to collaborate on helping and advising the patient.
i. Involve the partner or another family member.
j. Listen to the patient.

Page | xv
D. ADVERSE EFFECTS AND INTERACTIONS
1. ADVERSE DRUG REACTIONS (ADR)
• Any response to a medicine that is noxious, unintended, and occurs
at doses normally used for prophylaxis, diagnosis, or therapy.
• These reactions are different from accidental/deliberate excessive
dosage or medicine maladministration.
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS
a. EXTREMES OF AGE
• The very old and the very young populations are more
susceptible to ADRs.
o Examples of which are: hypnotics, antihypertensives,
Non-Steroidal Anti-inflammatory Drugs (NSAIDs),
psychotropics, diuretics, and digoxin.
• All children, particularly neonates, differ from adults in their
response to medicines.
o Some medicines are likely to cause problems in
neonates but are generally tolerated in children.
o Other medicines are associated with an increased risk
of ADRs in children of all ages.
b. INTERCURRENT ILLNESSES/COMORBIDITIES
• This occurs when a patient suffers from another disease aside
from the current condition being treated (kidney, liver, or heart
disease). The genetic make-up of the individual patient plays
a role.
c. MEDICINE INTERACTIONS
• These may occur among medicines that compete for the same
receptor, or which act on the same physiological system.
• These may occur indirectly when a medicine-induced disease,
or a change in fluid/electrolyte balance, alters the response to
another medicine.
• These may occur when one medicine alters the absorption,
distribution, or elimination of another medicine, such that the
amount which reaches the site of action is either increased or
decreased.

Drug-drug interactions are some of the most common

causes of adverse effects. When two medicines are administered to
a patient, they may either act independently of each other or interact
with each other. The interaction may increase or decrease the effects

Page | xvi
 of the medicines concerned and may cause unexpected toxicity. As
newer and more potent medicines become available, the frequency
of serious drug interactions is likely to increase.
NOTE: Interactions that modify the effects of a medicine may
involve non-prescription medicines, non-medicinal chemical agents,
and social drugs such as alcohol, marijuana, and tobacco, and
traditional remedies, as well as certain types of food. The
physiological changes in individual patients, caused by such factors
as age and sex, also influence the predisposition to ADRs resulting
from drug interactions.
d. INCOMPATIBILITIES BETWEEN MEDICINES AND IV FLUIDS
• Medicines should not be added to blood, amino acid solutions,
or fat emulsions.
o Certain medicines, when combined with intravenous
fluids, may be inactivated by pH changes, precipitation,
or chemical reaction.
e. ADVERSE EFFECTS CAUSED BY TRADITIONAL MEDICINES
Patients who have been, or are taking, traditional herbal
remedies may develop ADRs. In these types of preparation, it is not
always easy to identify the responsible constituents. Refer to the
medicine and toxicology information service if available or to suitable
literature.
f. EFFECT OF FOOD ON MEDICINE ABSORPTION
Food delays gastric emptying and reduces the rate of
absorption of many medicines; however, the total amount of
medicine absorbed may or may not be reduced. On the other hand,
some medicines are taken with food, either to increase absorption or
to decrease the irritant effect on the stomach.
E. PRESCRIPTION WRITING
1. PRESCRIPTION FORM
Administrative Order No. 62 (series of 1989) on the rules and
regulations to implement prescribing requirements under the Generics Act
defines a prescription as a written order and instruction of a validly
registered physician, dentist, or veterinarian for the use of specific medicine
(or medical device) for a specific patient.
The most important requirement for a prescription is that it should
be clear. It should be legible and indicate precisely what should be given.
The language used may be in English, Filipino, or the local dialect.
Pursuant to R.A. No. 5921, or the Pharmacy Act as amended, all
prescriptions should contain the following information:
• The patient’s name, age, and sex;
Page | xvii
 • The prescriber’s name, office address, professional registration
number, and professional tax receipt number; and
• Date of the prescription
• In addition, Section 3 of the Generics Act lists the following specific
guidelines to prescribing:
o Generic names shall be used in all prescriptions. For drugs with
a single active ingredient, the generic name of that active
ingredient shall be used in prescribing. For drugs with two or
more active ingredients, the generic name as determined by
the Philippine FDA shall be used.
o The generic name must be written in full, but the salt or
chemical form may be abbreviated. (The symbol Rx means
prescription which originated in medieval manuscripts as an
abbreviation of the Latin verb recipe. The imperative form is
recipere which means “to take” or “take thus.”)
o The generic name must be clearly written immediately after the
Rx symbol or on the order chart.
o A brand name may also be included. If written on a prescription
pad, the brand name must be enclosed in parentheses and
written below the generic name. If written on a patient’s chart,
it must be enclosed in parentheses and written after the
generic name. Department Memorandum No. 2009-0009
(Generics Only Prescribing) was issued on 07 January 2009
prohibiting government physicians to prescribe branded
medicines.
o The pharmaceutical form (e.g., “tablet”, “oral solution”, “eye
ointment”) should also be stated.
o The strength of the medicine should be stated in standard units
using abbreviations that are consistent with the Système
International (SI) [Refer to Appendices for abbreviations and
symbols].
o Avoid decimals whenever possible. If this is unavoidable, a zero
should be written before the decimal point.
2. INCORRECT PRESCRIPTIONS
Three types of incorrect prescriptions may be identified:
a. Erroneous prescription:
• Where the brand name precedes the generic name
• Where the generic name is the one in parentheses
• Where the brand name is not in parentheses
b. Violative prescription:
Page | xviii
 • Where the generic name is not written
• Where the generic name is illegible, and a legible brand name
is written
• Where the brand name is indicated and instructions added
(such as the phrase “no substitution”) which tend to obstruct,
hinder, or prevent proper dispensing
c. Impossible prescription:
• When only the generic name is written, but it is not legible
• When the generic name does not correspond to the brand name
• When both the generic and brand names are not legible
• When the drug product prescribed is not registered with the
Philippine Food and Drug Administration
If an erroneous prescription is received, the prescription may be filled but it
should be kept and reported to the nearest Department of Health (DOH) office for
appropriate action. On the other hand, violative and impossible prescriptions are
not to be filled and should also be kept and reported to the nearest DOH office.
3. NARCOTICS AND CONTROLLED SUBSTANCES
The prescribing of a medicinal product that is prone to abuse requires
special attention and may be subject to specific statutory requirements.
Practitioners may need to be authorized to prescribe controlled substances. In
such cases, it might be necessary to indicate details of the authority on the
prescription.
In particular, the strength, directions, and quantity of the controlled
substance to be dispensed should be stated clearly, with all quantities are written
in words, as well as in figures to prevent alteration. Other details, such as patient
particulars and dates, should also be filled in carefully to avoid alteration.

Page | xix
F. PATIENT COUNSELING
This is a one-on-one, dynamic interaction between a health care practitioner
and a patient and/or caregiver, which should include an assessment if the
information was received as intended, and that the patient understands how to
use the information to improve the probability of positive therapeutic outcomes.
1. WHAT TO COUNSEL
Routinely, effectively and appropriately educate patients on the
following: (1) when dispensing prescription and non-prescription drugs, (2)
when counseling on discharge medications, and (3) when providing
recommendations about the management of specific drug-related
problems:
a. The medication’s name (generic), indication, and when appropriate
to use
b. The medication’s expected onset of action and what to do if the
action does not occur
c. The medication’s route, dosage form, dosage, and administration
schedule (including duration of therapy)
d. Directions for use including education about drug devices
e. Proper storage requirements
f. Common or important drug-drug or drug-food interactions
g. Potential common and severe adverse effects, and actions to
prevent or minimize their occurrence
h. What the patient should do to monitor his/her therapeutic response
or when side effects develop
i. What actions the patient should take if the intended therapeutic
response is not obtained or if side effects develop
j. Proper disposal of contaminated, discontinued, or unused
medications
2. WHO AND WHEN TO COUNSEL
a. Patients who should always be counseled together with their families
and caregivers:
• Confused patients
• Patients who are sight- or hearing-impaired
• Patients with poor literacy
• Patients whose profiles show a change in medications/dosing
• New patients, or those receiving a medication for the first time

Page | xx
 • Patients who have medications with significant side effects,
specific storage requirements, and complicated directions

b. Patients who should be counseled at certain intervals together with their

families and caregivers:
• Asthmatic patients
• Diabetic patients
• Patients taking four (4) or more prescribed medications
• Patients who are mentally ill
• Epileptic patients
• Patients with skin complaints
3. COUNSELING: PROCESS STEPS
Steps in patient education and counseling process will vary according
to the health system’s policies and procedures, environment, and practice
setting. Generally, the following steps are appropriate for patients receiving
new medications or returning for refills:
a. Establish a caring relationship with the patient as appropriate to the
practice setting, and stage in the patient’s health care management.
Show interest in the patient verbally and non-verbally.
• Explain the purpose and expected length of sessions.
• Obtain the patient’s agreement to participate.
b. Assess the patient’s knowledge about his or her health problems,
medications, physical and mental capability to use the medications
appropriately, and attitude towards the health problems and
medications.
• Ask why the patient is being prescribed the medication (if
known), or the medication’s use, expected benefits, and
action.
• Provide information orally, and use demonstrations or visual
aids to fill the patient’s gaps in knowledge and understanding.
• Open the medication containers and show the patient what
the medication looks like, or demonstrate use.
• Explain how to take the medication.
• Discuss when to take, and how long to take the medication.
• Plan what to do if a dose is missed.
• Determine any special precautions to heed and follow.
• Explain how to store the medication.

Page | xxi
 • Demonstrate if the prescription can be refilled, and if so,
determine when it is done.
• Give specific details on how the patient will know if the
medication is working.
c. Verify patient’s knowledge and understanding of medication use.
• Ask the patient to describe (or show) how the medication
should be used, and its effects.
• Ask the patient if they have any questions.

Page | xxii
 UPDATES IN ANTIMICROBIAL RESISTANCE
A. DEFINITION OF ANTIMICROBIAL RESISTANCE
1. Antimicrobial Resistance (AMR) refers to the resistance of a
microorganism (including bacteria, viruses, and some parasites) to
an antimicrobial agent to which it was previously sensitive. Resistant
organisms withstand attack by antibacterial, antiviral, or antimalarial
agents. Thus, standard treatments become ineffective, allowing
infections to persist and spread.

2. Antimicrobial resistance poses a serious public health threat

because of its implications on health care and the increase in
economic burden.
3. Although AMR is a natural phenomenon that develops when the
organism mutates or acquires a resistance gene, its emergence has
been accelerated by the overuse and misuse of antimicrobial agents.

B. CAUSES OF ANTIMICROBIAL RESISTANCE

1. The ultimate causes of AMR are microbial, clinical, and programmatic
in nature. However, it is essentially a man-made occurrence.
2. The proliferation of drug-resistant strains is associated with various
management, healthcare provider, and patient-related issues. Table
1 enumerates several of the causes leading to drug resistance.
Table 1. Causes of inadequate treatment may contribute to the emergence of drug
resistance.
Healthcare providers: Drugs: Patients:
Inadequate regimens Inadequate supply/quality Inadequate drug intake
Inappropriate guidelines Poor quality Poor adherence
Noncompliance with Unavailability of certain (or poor directly observed therapy)
guidelines drugs Lack of information
Absence of guidelines (stock-outs or delivery Lack of money
Poor training disruptions) (no treatment available free of
No treatment monitoring Poor storage conditions charge)
Poorly organized or funded Wrong dose or combinations Lack of transportation
control programs Adverse effects
Social barriers
Malabsorption
Substance dependency disorders
Source: Final Report, Country Situation Analysis on Antimicrobial Resistance, Philippines, 2012.

3. The general categories of the causes, i.e., therapeutic protocols, drug

characteristics, and drug selling and purchasing practices, provide
opportunities where potential strategies to combat AMR arise.

Page | xxiii
 C. ANTIMICROBIAL RESISTANCE: A GROWING GLOBAL CONCERN
1. The WHO cites the following alarming reasons why AMR is already a
global concern: AMR kills; AMR challenges the control of infectious
disease; AMR threatens a return to the pre-antibiotic era; AMR
increases the costs of health care; AMR jeopardizes healthcare gains
to society; and, AMR compromises health security, as well as
damages trade and economy.
2. Furthermore, the following facts collated by WHO demonstrate the
potential and real dangers that AMR causes and has caused:
a. The WHO Global Report 2019 noted that in the year 2018,
there were about 484,000 new cases worldwide who had
rifampicin-resistant tuberculosis (RR-TB), of which 78% had
multi-drug resistant tuberculosis (MDR-TB). The estimated
rate of MDR/RR TB incidence is 6.4 per 100,000 population.
In 2018, there were about 214,000 deaths from MDR/RR-TB.

MDR-TB is defined as resistance to rifampicin and isoniazid.

Its therapy requires 18-24 months of treatment with
expensive second-line drugs, like capreomycin and
kanamycin.

On a global level, the MDR/RR-TB among TB patients averages

to 3.4% in the new and 18% among the re-treatment cases

b. Extensively drug-resistant TB or XDR-TB (defined as MDR plus

resistance to any member of the quinolone family and at least
to any second-line anti-TB injectable, such as kanamycin,
capreomycin, or amikacin) is a global threat with a case-
fatality rate of 50%.

XDR-TB is a big problem because there are very few options

for treatment, which probably accounts for the high mortality
rate among XDR-TB patients.

Among the 40 countries with a high TB or MDR-TB burden, 24

had data from the past 15 years on resistance to second-line
anti-TB drugs. The proportion of MDR/RR-TB cases with
resistance to any fluoroquinolone for which testing was done
– including ofloxacin, levofloxacin, and moxifloxacin –
reported in the WHO 2019 Report was 20.8% (95% CI: 16.3 –
25.8%) in 2018.

Page | xxiv
c. Resistance to earlier generation antimalarial medicines such
as chloroquine and sulfadoxine-pyrimethamine is widespread
in most malaria-endemic countries. Falciparum malaria
parasites resistant to Artemisinin-based Combination Therapy
(ACT) have now emerged in Southeast Asia where infection
showed delayed clearance after the start of treatment,
indicating resistance.

Important causes of anti-malarial drug resistance include the

unusual genetic structure of the parasites in regions with drug
resistance; counterfeit or substandard treatments;
unregulated or poorly administered antimalarial drug use; and
artemisinin drug use without proper complementary
treatment.

d. Ciprofloxacin is the antibiotic currently recommended by WHO

for the management of bloody diarrhea due to Shigella, now
that widespread resistance has developed to any previously
effective antibiotics. But rapidly increasing prevalence of
resistance to Ciprofloxacin in Shigellosis is reducing the
options for safe and efficacious treatment especially for
children. New antibiotics suitable for oral use are badly
needed.

e. AMR has become a serious problem for the treatment of

gonorrhea (caused by Neisseria gonorrhoeae), which is
increasing in prevalence worldwide. In multidrug-resistant N.
gonorrhoeae (MDR-GC), resistance is found against
tetracyclines, macrolides (including azithromycin),
sulfonamide, trimethoprim combinations, and more recently,
to quinolones. Extensively drug-resistant gonococci (SDR-GC)
have also emerged.

The problem of AMR now involves even the “last-line”

cephalosporins, with worrisome trends of declining
susceptibility to these drugs in many parts of the world. This
is particularly alarming due to the rising global rates of
gonorrhea. The current options for therapy are the third
generation extended-spectrum cephalosporins (cefixime,
ceftriaxone) and azithromycin.

Untreated gonococcal infections will result in higher rates of

illness that include pelvic inflammatory disease, ectopic
pregnancy, chronic pelvic pain and infertility in women, and
epididymitis in men. Gonococcal infection can also increase
the risk of HIV acquisition and transmission.
Page | xxv
 f. Extended-spectrum beta-lactamases or ESBLs are resistant to
third-generation cephalosporins (ceftazidime, cefotaxime,
and cefpodoxime) as well as monobactams (aztreonam);
common in the Enterobacteriaceae, particularly E. coli and K.
pneumoniae.

g. New resistance mechanisms, such as the beta-lactamase

NDM-1 (New Delhi Metallo beta-lactamase 1), have emerged
among several gram-negative bacilli. These bacilli are
considered as new superbugs that have resistance to broad-
spectrum antibiotics that are often the last defense against
multi-resistant bacterial strains.

h. A high percentage of hospital-acquired infections is caused by

highly resistant bacteria such as methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant
enterococci.

i. Resistance is an emerging concern for the treatment of HIV

infection, following the rapid expansion in access to anti-
retroviral medicines in recent years.

D. STATUS OF ANTIMICROBIAL RESISTANCE IN THE PHILIPPINES

1. There is a need to approach the problem of AMR in the Philippines

with a heightened sense of urgency. This is elucidated by several
pieces of evidences of the dangers it poses.
a. The most dreaded recognized AMR gene, the NDM-1, was
identified in the Escherichia coli isolated from the urine of a
patient in 2011. The gene can render even the most powerful
antibiotics ineffective.

b. Many of the causative bacterial pathogens that cause

infections included in the top ten causes of morbidity in the
Philippines have already become resistant to multiple
antibiotics.

At the forefront in the country is tuberculosis, with MDR-TB and

XDR-TB already present in the Philippines. According to the
WHO 2019 Global Tuberculosis Report, the country ranked 4th
among countries with the highest incidence of TB. The
Philippines’ estimated total TB incidence was 591,000 in 2018.

Page | xxvi
 With a population of 107 million, the country’s TB incidence
rate stands at 554 per 100,000 persons which is much higher
than the global average of 130 per 100,000 persons.

In the Philippines, the MDR/RR-TB incidence is 17 per 100,000

population. The estimated proportion of TB cases with
MDR/RR-TB in 2018 was 1.7% in new cases and 16% in
previously treated cases.

c. The alarming increase in the trends of AMR in the country is

demonstrated in Table 2 which summarized the results of a
comparison of the antimicrobial resistance of selected
organisms in 1993 and 2011.

Page | xxvii
Table 2. Summary of Antimicrobial Resistance Patterns for Selected Organisms and
Antimicrobials in 1993 and 2011.
Percent (%) Resistance
Organism/Antimicrobials
1993 2011 Remark

Enteric Infections/Gram-negative Pathogens

1. E. coli
Ampicillin 67.5 80.0 Increased
NDM: identified VERY
ESBLs – ALARMING
increasing
2. Non-typhoidal Salmonella
Ampicillin 33.4 30.0 Decreased
Cotrimoxazole 34.3 21.0
Chloramphenicol 25.7 7.0
3. Salmonella typhi
Ampicillin 5.4 0.6 Decreased
Cotrimoxazole 10.2 0
Chloramphenicol 5.5 0
4. Shigella flexneri/spp.
Ampicillin 62.5
Cotrimoxazole 30.3 79.0 Increased
Chloramphenicol 53.1
Nalidixic acid 4.0 Emerging
Ciprofloxacin 3.0
5. Klebsiella spp.
Cephalothin (Cefazolin) 36.6 ESBL confirmed VERY
(from 18 tertiary ALARMING
sentinel sites)
Gentamicin 26.9
6. Vibrio cholerae
Cotrimoxazole 43.0
Tetracycline 5.1 5.0 (zero in NOT GOOD
2010)
7. Neisseria gonorrhoeae
Ofloxacin 81.0 VERY
ALARMING
Ciprofloxacin 82.0
Penicillin 91.7
Tetracycline 44.1

Acute Respiratory Infections/Gram-positive Pathogens

1. Streptococcus pneumoniae
Cotrimoxazole 6.5/8.7 16.0 Increased
Chloramphenicol 7.7 2.0 Decreased
Penicillin 24.4 4.0 Decreased
2. Staphylococcus aureus
Cotrimoxazole 13.4
Erythromycin 20.0

Page | xxviii
 Methicillin/Oxacillin 18.5 53.0 VERY
ALARMING
3. S. epidermidis
Cotrimoxazole 35.2 52.0 VERY
ALARMING
Erythromycin 42.0 51.0
Methicillin/Oxacillin 38.4 66.0

Multidrug Resistant / Hospital-Acquired Pathogens

1. Acinetobacter baumannii 50% of isolates
are MDR
VERY, VERY
No data (resistant to at
ALARMING
least 3 classes of
antimicrobials;
13% to ALL but 1
or 2 classes as
reported by 21
sentinel sites;
43% associated
with HAI)
2. Pseudomonas aeruginosa
Amikacin 26.8 Resistant to at VERY, VERY
least 3 classes of ALARMING
antimicrobials;
43% associated
with HAI
Gentamicin 53.7

2. The DOH established in 1988 the Philippine Committee on

Antimicrobial Resistance Surveillance Program (ARSP) to determine
the current status and developing trends of antimicrobial resistance
of selected aerobic bacteria to specific antimicrobials.

The DOH-ARSP is a sentinel laboratory-based antimicrobial

resistance surveillance on aerobic bacteria from priority clinical
specimens sent routinely to the sites.

The ARSP, which now has 24 active sentinel sites in tertiary or

regional hospitals in 16 regions, submits and publishes annual
summary reports. The DOH-ARSP also collects data from 2
gonorrhoeae surveillance sites. The data which it publishes have
been used in the development of clinical practice guidelines and
policies in the control of resistant infections

The interpretation of the antimicrobial resistance data must be

approached with caution due to factors that can introduce bias and
influence analysis (e.g., area and population coverage, sampling, and

Page | xxix
 laboratory routines and capacities). However, the surveillance
program focuses on aerobic bacterial pathogens that cause common
infectious diseases that are of public health importance. Thus, all
primary healthcare prescribers must keep abreast of the new
antimicrobial susceptibility data to enable them to select appropriate
treatment options.
3. Antimicrobial Resistance Surveillance Program: 2019 Annual Report
(Antimicrobial Resistance Surveillance Program Annual Report –
2019, Manila, ARSP, 2020):

a. Overview:

The resistance data for 100,334 bacterial isolates submitted

to the ARSP reference laboratory by the 24 sentinel sites and 2
gonorrhea surveillance sites from 16 out of 17 regions were
reported and analyzed for the year 2019. The most common
specimen types were respiratory (30.2%), blood (23.9%), urine
(18.5%), and wound (16.4%). Other specimen types
contributing to the 2019 data were: tissues (4.4%), fluids (3.5%
which include the cerebrospinal and other fluids), and other
specimens (3.1% that include genital specimens and stool). A
majority (55.5%) of the isolates were from presumptively
community-acquired infections (specimen date was 2 days or
less from admission date or specimens from OPD or ER
patients). Many of the isolates were from patients from Medical
Department (31.2%).

The most commonly isolated bacterial pathogens from all

specimen types for 2019 were: Klebsiella pneumoniae,
followed by Escherichia coli and Pseudomonas aeruginosa.
The most commonly isolated bacteria by specimen type are
seen in the following table:

Page | xxx
Table 3. Most commonly isolated bacterial pathogens by specimen type
(ARSP 2019).
Most Common Bacterial Isolates by Specimen Type (2019)
Respiratory Specimen: Blood:
Klebsiella pneumoniae Staphylococcus sp.,
Pseudomonas aeruginosa coagulase-negative
Haemophilus influenzae Staphylococcus aureus
Klebsiella pneumoniae
Cutaneous or Wound: Stool:
Staphylococcus aureus Salmonella species
Escherichia coli Shigella species
Klebsiella pneumoniae Aeromonas species

Cerebrospinal Fluid: Urine:

Staphylococcus sp., Escherichia coli
coagulase-negative Klebsiella pneumoniae
Acinetobacter baumannii Staphylococcus sp., coagulase-
Pseudomonas species negative

Source: Antimicrobial Resistance Surveillance Program: 2019 Annual Report. DOH – ARSP, 2019.

The ARSP 2019 Report confirmed the persistence of

antimicrobial resistance among most of the aerobic bacterial
pathogens that are of public health concern analyzed in 2019.

Increasing AMR trends were noted for many of the pathogens

included in the surveillance reports for the past years. Among
the findings highlighted in the 2018 Annual Report were:
• Although methicillin resistance was observed to be
decreasing among Staphylococcus aureus isolates,
the resistance rate remains over 50% limiting the
use of this previously effective antibiotic in the
treatment of infections due to these bacteria.
• The high rates of multidrug resistance among
common pathogens such as Escherichia coli,
Klebsiella pneumoniae, Pseudomonas aeruginosa,
and Acinetobacter baumannii makes treatment of
infections due to these bacteria challenging.
• Emerging penicillin resistance among
Streptococcus pneumoniae has to be carefully
validated to prevent and control this emerging
resistance.

Page | xxxi
 b. Summary of Findings in the 2019 Annual Report:

The resistance data analyzed by the ARSP for 2019 for each of
the bacterial pathogens are summarized as follows (ARSP-
2019 Annual Report):

1) Streptococcus pneumoniae
The cumulative resistance rate of S. pneumoniae isolates
from all specimen types reported for 2019 against
penicillin, using meningitis breakpoints, was at 13.4%
(n=404) and 0.5% using nonmeningitis breakpoints.
When the pneumococcal isolates were analyzed by
specimen type, penicillin resistance using meningitis
breakpoints was at 10.6% for invasive (blood) isolates and
15.0% for non-invasive isolates (respiratory). Using non-
meningitis breakpoints, penicillin resistance was at 0.8%
for the non-invasive isolates (respiratory). The most
common invasive S. pneumoniae serogroups/serotypes
identified for 2019 were 3, 1, 10, and 5.

2) Haemophilus influenzae
Resistance rates against the panel of antibiotics for 2019
isolates of H. influenzae are highest for ampicillin at
10.2% (n=432). There were no reports of cefuroxime or
azithromycin-resistant H. influenzae for 2019.

3) Salmonella enterica serotype Typhi

S. enterica serovar Typhi isolates have remained
susceptible to first-line antibiotics with reported resistant
isolates at 3.9% or less for cefotaxime, ampicillin, co-
trimoxazole, and chloramphenicol for 2019. There was no
reported confirmed ciprofloxacin-resistant isolate for
2019.

4) Nontyphoidal Salmonella
Resistance rate of nontyphoidal Salmonella was at 9.8%
for ciprofloxacin (n=214) and 8.8% for ceftriaxone
(n=226). The most common nontyphoidal Salmonella
species serovar identified for 2019 were S. enterica
serotype Enteritidis and S. enterica serotype
Typhimurium.

5) Shigella species
Data in 2019 showed increased resistance to ampicillin
at 68.2% (n=44) and co-trimoxazole at 60.5% (n=43).

Page | xxxii
 Resistance of Shigella species to ciprofloxacin and
ceftriaxone were at 2.4% and 9.3%, respectively.

6) Vibrio cholerae
Vibrio cholerae isolates remain susceptible to first-line
agents: chloramphenicol, co-trimoxazole, and tetracycline
with 5% or less reported resistance rates for 2019.

7) Neisseria gonorrhoeae
N. gonorrhoeae isolates have high rates of resistance
against ciprofloxacin at 79.4% (n=131), and tetracycline
at 58% (n=131). Three (3) isolates were non-susceptible
to azithromycin, one of which was confirmed to be non-
susceptible to azithromycin in the ARSRL.

8) Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) rate
for 2019 was at 52.1% (n=7,189). Although not
statistically significant, the observed decrease in oxacillin-
resistance for 2019 is a continuation of the decrease in
the rates observed in the last 2 years. Resistance rates in
2019 against antibiotics used for treatment of S. aureus
infections were as follows: 35.5% for co-trimoxazole
(n=7,040); 10.4% for clindamycin (n=7,323); 3.2% for
rifampicin (n=5,867); 0.6% for linezolid (n=6,512); and
0.8% for vancomycin (n=6,512).

9) Enterococcus species
Rates of E. faecalis resistance was at 2% (n=1,900) for
linezolid and 1.6% (n=2,094) for vancomycin. Rates of E.
faecium resistance was at 1.6% (n=1,233) for linezolid
and 12.1% for vancomycin (n=1,290).

10) Escherichia coli

E. coli rates of resistance against the fluoroquinolones
and third generation cephalosporins were at 46.6% for
ciprofloxacin (n=10,946) and 39.9% for ceftriaxone
(n=11,081). Resistance to carbapenems continue to rise
with rates against ertapenem at 5% (n=9,833); imipenem
at 6% (n=9,978) and meropenem at 6.4% (n=10,961). E.
coli extended-spectrum β –lactamase (ESBL) suspect
rates for 2019 was at 53.25% (n=5,639).

11) Klebsiella pneumoniae

Resistance to the carbapenems continue to rise with
2019 K. pneumoniae resistance rates as high as 13.5%
for meropenem (n=13,912); 12% for imipenem
Page | xxxiii
 (n=13,394) and 10.2% for ertapenem (n=11,976). K.
pneumoniae extended-spectrum β – lactamase suspect
(ESBL) rates for 2019 was at 55.2% (n=8,154).

11) Pseudomonas aeruginosa

For 2019, carbapenem resistance was reported at 16.9%
and for imipenem (n=7,014) and 14.2% for meropenem
(n=7,702) for P. aeruginosa.

12) Acinetobacter baumannii

For 2019, more than 50% of the reported A. baumanii
isolates were resistant to several antibiotics: cefepime at
58.1% (n=5,747); imipenem at 55.8% (n= 5,128);
meropenem at 56.8% (n=5,750); ciprofloxacin at 56%
(n=5.696); and co-trimoxazole at 52.6% (n=5,247).

13) Multidrug-Resistant Pseudomonas aeruginosa and

Acinetobacter baumanii
P. aeruginosa Multi-Drug Resistance (MDR) and possible
Extensive-Drug Resistance (XDR) rates for all isolates were
at 18% and 14 % respectively.
A. baumanii MDR and possible XDR rates for all isolates
were at 58% and 47%, respectively.

E. RECOMMENDATIONS OF THE DOH ANTIMICROBIAL RESISTANCE

SURVEILLANCE PROGRAM

Based on the latest published Antimicrobial Resistance Surveillance

Report for 2019, recommendations of the ARSP regarding antibiotic
treatment for aerobic bacterial pathogens of public health importance
were as follows (ARSP 2019 Annual Report):

1. Infections secondary to Streptococcus pneumoniae can still be

covered with penicillin, although there is a need to closely monitor
the changing trends of resistance among pneumococci. Improving
the surveillance to include clinical outcomes data for invasive
isolates as well as routine pneumococcal serotyping will allow for
better monitoring and evaluation of the government’s vaccination
strategy for this vaccine-preventable pathogen.

2. Given the high resistance rate of Hemophilus influenzae to

ampicillin, recommended empiric treatment for suspected H.
influenzae infections consists of beta-lactam/beta-lactamase
inhibitor combinations and extended-spectrum oral cephalosporins.

Page | xxxiv
3. Empiric treatment for suspected uncomplicated typhoid fever could
still consist of either chloramphenicol or co-trimoxazole or
amoxicillin/ampicillin. Microbiological and antimicrobial
susceptibility data is recommended to aid in pathogen-directed
therapy.

4. In Salmonella gastroenteritis, increasing rates of ciprofloxacin

resistance should remind clinicians to use antibiotics judiciously, as
this is usually a self-limited disease.

5. Given the emerging resistance of Shigella to quinolones and limited

data available, more vigilant surveillance of the resistance pattern of
this organism should be pursued by encouraging clinicians to send
specimens for culture.

Tetracycline, chloramphenicol, and co-trimoxazole remain good

treatment options for cholera cases.

6. For Neisseria gonorrhoeae, based on the 2018 report, ceftriaxone

remains as an empiric antibiotic of choice for gonococcal infections.
More vigilant surveillance of the resistance patterns of this organism
should be pursued by encouraging clinicians to send specimens for
culture and confirmatory testing at the reference laboratory.
Enhanced clinical data could also provide evidence for
recommendations on possible stratified therapy. Surveillance
among stable populations such as symptomatic males may help
provide further information on the development of antibiotic
resistance among Neisseria gonorrhoeae.

7. A decrease in MRSA rates was noted for 2019. Linking laboratory

information with clinical data as well as genotyping to identify strains
of prevalent MRSA isolates will allow for targeted and comprehensive
strategies in MRSA containment.

8. Multidrug-resistance among the bacterial organisms Pseudomonas

aeruginosa and Acinetobacter baumannii continues to be a public
health concern because of the limited treatment options and
infection control challenge in containment. Real-time data analysis
and genotyping to establish linkages will allow for timely isolation and
infection control interventions. Stratified, institute-specific
antibiograms will allow clinicians to identify the best empiric
antibiotic

Page | xxxv
 All readers are enjoined to refer to the yearly published ARSP surveillance
data for more updated information and proper guidance (see Directory for
complete contact details).

F. DRIVING FORCES BEHIND ANTIMICROBIAL RESISTANCE

1. The inappropriate and irrational use of medicines provides
favorable conditions for resistant microorganisms to emerge and
spread. WHO enumerates the following as the underlying factors
that drive AMR:
a. Inadequate national commitment to a comprehensive,
coordinated response, ill-defined accountability, and
insufficient engagement of communities;
b. Weak or absent surveillance and monitoring systems;
c. Inadequate systems to ensure quality and uninterrupted
supply of medicines;
d. Inappropriate and irrational use of medicines, in both clinical
practice and animal husbandry, and aquaculture;
e. Poor infection prevention and control practices; and
f. Depleted arsenals of diagnostics, medicines, and vaccines
as well as insufficient research and development of new
products.

G. THE RESPONSE OF THE NATIONAL GOVERNMENT TO THE

RISING ANTIMICROBIAL RESISTANCE
1. In 2014, the Philippine government organized the Inter-Agency
Committee on Antimicrobial Resistance (ICAMR). The committee was
led by the Department of Health and co-led by the Department of
Agriculture. The ICAMR facilitated the development of the National
Action Plan to Combat AMR 2015-2017, which was launched in May
2015.

2. As a follow-through to the Philippine Action Plan to Combat AMR

2015-2017, the ICAMR developed the Philippine National Action Plan
on AMR 2019- 2023, which outlines the following key strategies:
a. Commitment to the Philippine National Action Plan through
multisectoral engagement and accountability.
b. Strengthening of surveillance and laboratory capacity
c. Ensuring uninterrupted access to safe and quality-assured
antimicrobials
d. Regulation and promotion of the optimal use of antimicrobials
Page | xxxvi
 e. Implementation of appropriate measures to reduce infection
across all settings
f. Promoting innovation and research on AMR
g. Improvement of the awareness and understanding of
antimicrobial resistance through effective communication and
education.

H. ACTION PLANS THE PRIMARY PHYSICIANS AND DENTISTS CAN ADOPT TO

HELP COMBAT ANTIMICROBIAL RESISTANCE
1. Assuring the judicious use of antimicrobial agents through faithful
adherence to the principles of rational use of medicines and utilizing
antimicrobial agents only for the appropriate indications as
recommended by the Antimicrobial Resistance Surveillance Program
(ARSP) or the task force for Clinical Practice Guidelines and included
in the Philippine National Formulary.

The choice of antibiotics must strictly conform to the best standard

treatment or clinical practice guidelines, and be guided by the latest
findings and recommendations of the ARSP;
2. Keeping abreast of the latest information on Antimicrobial
Resistance (AMR) through review of the latest antibiotic susceptibility
data published by the ARSP, literature search, attendance in
seminars, and participation in continuing medical education
programs;
3. Devoting sufficient time to educate the patients and their families
and caregivers about the appropriate use of antibiotics and the
reasons behind the need for strict adherence to the prescribed
dosage schedule and completion of the full course of treatment as
well as to educate them on the prevention of AMR;
4. Careful monitoring of the patient’s compliance and response to the
antimicrobial agents;
5. Submitting specimen for culture when indicated (e.g. for suspected
gonococcal infections);
6. Complying with the rules on prescribing, and other regulations in the
Pharmacy Law;
7. Developing better communication with pharmacists and other
persons authorized to dispense medicines;
8. Educating the other healthcare providers (nurses, midwives,
barangay health workers) about the RUM and prevention of AMR;
and,
9. Educating the community continually on the need for and proper
ways of maintaining good personal hygiene and sanitation,
Page | xxxvii
 avoidance of vices or unhealthy habits, sanitation and prevention of
infections, including maintaining the cleanliness of their
surroundings.

Page | xxxviii
 RELEVANT LAWS, REGULATIONS & POLICIES

The 1987 Philippine Constitution mandates the right of every Filipino to health.
It enunciates the policy that “the State shall protect and promote the health of the
people and instill health consciousness among them” (Article II Section 15).
Furthermore, it provides the adoption by the State of an “integrated and
comprehensive approach to health development which shall endeavor to make
essential goods, health and other social services accessible to all the people at
affordable cost.”

In pursuit of these goals, several policies and laws have been enacted. A clear
understanding of the statutes and conformity to regulations by all healthcare providers
underpin the attainment of optimal heath management. The important ones that
pertain to the Formulary and the mandatory prescribing practices are summarized in
the subsequent sections. Of particular relevance are the National Health Insurance Act
of 2013 and Administrative Order 2012-0023 and its amendments, which included
provisions that relate to the objectives of this current volume of the Formulary.

• Republic Act No. 6675, known as the Generics Act of 1988 which
declared as the policy of the State, among others, “to promote,
encourage and require the use of generic terminology in the importation,
manufacture, distribution, marketing, advertising and promotion,
prescription and dispensing of drugs; to ensure the adequate supply of
drugs with generic names at the lowest possible cost; to emphasize the
scientific basis for the use of drugs, in order that the health professional
may become more aware and cognizant of their therapeutic
effectiveness; and to promote drug safety.”

As contained in Section 6 of RA 6675 those required to use the

generic terminology are as follows: (a) all government health agencies
and their personnel as well as other government agencies in all their
transactions related to purchasing, prescribing, dispensing, and
administering of drugs and medicines; (b) all medical, dental, and
veterinary practitioners, and including private practitioners, who may
include brand names, if they so desire; (c) any organization or company
involved in the manufacture, importation, repacking and/or distribution
of drugs and medicines; and (d) drug outlets, including drugstores,
hospital and non-hospital pharmacies and non-traditional outlets such as
supermarkets and stores that shall inform any buyer about drug products

Page | xxxix
 having the same generic names, together with their prices, to allow the
buyers to exercise their options.

The Generics Act further states that “in the promotion of the
generic names for pharmaceutical products, special consideration shall
be given to drugs and medicines which are included in the Essential
Drugs List that will be prepared and updated regularly by the Department
of Health.

• Executive Order No. 49 enacted on January 21, 1993, directed the

mandatory use of the Philippine National Drug Formulary (Volume 1 or
the Essential Drugs List) as the basis for the procurement of drug
products by all concerned government entities. This strengthened the
advocacy of the Generics Act by ensuring that only essential medicines
identified in their generic names will be procured by all government
institutions.

• Administrative Order No. 163 s. 2002 (entitled “Implementing Guidelines

and Procedures in the Procurement and Requisition of Drugs and
Medicines by the Department of Health under Executive Order No. 49”)
provided the procedural bases that ensure requisition of essential
medicines by the government sector and the decision system for the
inclusion and deletion of medicines in the Philippine National Drug
Formulary (PNDF). This also set the requirements to be submitted for the
procurement of non-Formulary medicines as well as the criteria for the
approval of applications for exemptions from E.O. No. 49.

• The more recent Republic Act 9502 enacted in 2008 provides additional
power to the President of the Philippines to impose, upon the
recommendation of the Secretary of Health, maximum retail prices over
medicines that include, among others, the “drugs and medicines that are
included in the Philippine National Drug Formulary Essential Drug List.”

• The Philippine Health Insurance Corporation Board Resolution No. 265

(dated July 15, 1999) provides that the PNDF Volume I shall be the basis
for claims reimbursements for medicines.

• The National Health Insurance Act of 2013 (Republic Act No. 7875 as
amended by R.A. No. 9241 and RA No. 10606) declared as a guiding
principle the provision of comprehensive health care services to all
Filipinos through a socialized National Health Insurance Program that

Page | xl
 prioritizes the needs of the underprivileged, the sick, the elderly, persons
with disabilities (PWDs), women and children as well as provides for a full
national subsidy for the indigent families identified by the Department of
Social Welfare and Development. To ensure the quality of the health
services that will be rendered to members by the accredited providers,
the Republic Act states in Section 37 that all concerned health care
practitioners should assure that “the performance of medical procedures
and the administration of drugs are appropriate, necessary, and
unquestioningly consistent with accepted standards of medical practice
and ethics” as well as “respectful of local cultures.” Moreover, it
reiterated the previous requirement that medicines for which payment
will be made by PhilHealth shall be those included in the Philippine
National Drug Formulary except for explicit exemptions granted by the
Corporation.

• Administrative Order No. 2014-0009 entitled “Implementing Guidelines

of the Philippine Medicines Strategic Directions on Access to Medicines
for Filipinos (2011-2016) for the Rational Use of Medicines Pillar” was
enacted to set the guiding principles and key strategies that will
institutionalize the Rational Use of Medicines. Integrating RUM into the
healthcare system will ensure that only the most necessary and
scientifically proven, efficacious, and cost-effective medicines are used
in situations where there are clear and valid indications for them.

• The Rational Use of Medicines (RUM) forms an integral part of the

Philippine Medicines Strategic Directions on Access to Medicines for
Filipinos for 2011-2016, which will set the roadmap for a national
medicine policy. This policy will serve as the guideline for the
development of a framework that will provide the directions for improving
access to essential medicines by all Filipinos in all levels of healthcare at
all times. This incorporates the principles embodied in the SARAH
Medicines Access Framework that refers to five complementary and
mutually reinforcing pillars: Safety, efficacy, and quality; Affordability and
availability; Rational use of medicines; Accountability, transparency, and
good governance; and Health system support.

• Administrative Order No. 2016-0034 entitled “The New Implementing

Guidelines of the Philippine National Formulary System” retains the same
basic objectives as the previous PNFS policy, i.e., the description of
revised systems and procedures for the selection of medicines to be
included in or deleted from the Essential Medicines List and the
Page | xli
 development of the new format of the Philippine National Formulary. In
addition, it describes the system and processes for the promotion of the
use of the formulary among the different levels of healthcare managers
and providers, and consumers. The policy applies to all health facilities,
units, and offices of the entire government sector insofar as medicine
procurements are concerned and shall apply to the entire health sector
(both government and private) insofar as the Philhealth claims for
medicine reimbursements are concerned.

• Republic Act No. 11223: Universal Health Care Act (refer to the tabulated
summary of the objectives and key features of the Universal Health Care
Act on the following page).

Page | xlii
 Republic Act No. 11223: Universal Health Care Act

Page | xliii
Reference: Department of Health: Universal Health Care Act Primer
MEDICINE AND THERAPEUTIC
INFORMATION
 US FDA PREGNANCY RISK CATEGORIES

The FDA-assigned pregnancy categories as used in the Manual are as follows:

Category Interpretation

A CONTROLLED STUDIES SHOW NO RISK.

Adequate and well-controlled studies in pregnant women
have failed to demonstrate a risk to the fetus in the first
trimester of pregnancy (and there is no evidence of risk in
later trimesters).

B NO EVIDENCE OF RISK IN HUMANS.

Animal reproduction studies have failed to demonstrate a
risk to the fetus and there are no adequate and well-
controlled studies in pregnant women.

C RISK CANNOT BE RULED OUT.

Animal reproduction studies have shown an adverse effect
on the fetus and there are no adequate and well-controlled
studies in humans, but potential benefits may warrant use of
the drug in pregnant women despite potential risks.

D POTENTIAL EVIDENCE OF RISK.

There is positive evidence of human fetal risk based on
adverse reaction data from investigational or marketing
experience or studies in humans, but potential benefits may
warrant the use of the drug in pregnant women despite
potential risks.

X CONTRAINDICATED IN PREGNANCY.
Studies in animals or humans have demonstrated fetal
abnormalities and/or there is positive evidence of human
fetal risk based on adverse reaction data from investigational
or marketing experience, and the risks involved in the use of
the drug in pregnant women outweigh potential benefits.

Page | 1
 SYMBOLS and ABBREVIATIONS
ACE – Angiotensin-converting enzyme
ADR – Adverse drug reaction
AIDS – Acquired immunodeficiency syndrome
a.m. – Morning; before noon
Amp – Ampul
ARB – Angiotensin receptor blocker
AV – Atrioventricular
BCG – Bacille Calmette-Guérin (vaccine)
BP – Blood pressure
BPH – Benign prostatic hypertrophy
BSA – Body surface area
cap., caps. – Capsule
CFU – Colony-forming unit
CNS – Central nervous system
comp. – Compound
cr., crm. – Cream
CSF – Cerebrospinal fluid
D5NS – Glucose (dextrose) 5% in normal saline (0.9%)
D5W – Glucose (dextrose) 5% solution
dL – Deciliter
DOTS – Directly observed treatment, short-course
DMARD – Disease-modifying agents in rheumatoid disorders
DPI – Dry powder inhaler
ECG – Electrocardiogram
emuls. – Emulsion
EPS – Extrapyramidal syndrome
g – Gram
GERD – Gastroesophageal reflux disease
GFR – Glomerular filtration rate
GI – Gastrointestinal
gtt (s) – Drop (s)
h., hr. – Hour
HbA1c – Glycosylated hemoglobin
HIV – Human immunodeficiency virus
HRT – Hormone replacement therapy
HTN – Hypertension
ICP – Intracranial pressure
ID / (ID) – Intradermal

Page | 2
IM / (IM) – Intramuscular
Inj. – Injection
INR – International normalized ratio
IU – International unit/s
IV / (IV) – Intravenous
L – Liter
lin. – Liniment
lot. – Lotion
MAOI – Monoamine oxidase inhibitor
MDI – Metered dose inhaler
MDR-TB – Multidrug-resistant tuberculosis
mEq – Milliequivalent
mg – Milligram
mL – Milliliter
mmol – Millimole
MR – Modified release [includes Controlled Release (CR),
Extended Release (ER), Immediate Release (IR), Sustained
Release (SR), Long Acting (LA)]
nebul. – Spray
NSAID – Non-steroidal anti-inflammatory drug
p.m. – Evening
prn – As needed (from Latin pro re nata)
RE – Retinol equivalent
Resp. Soln. – Respiratory solution
SC / (SC) – Subcutaneous
SL / (SL) – Sublingual; under the tongue
Soln. – Solution
spp. – Species
SSRI – Selective serotonin reuptake inhibitor
supp. – Suppository
susp. – Suspension
syr. – Syrup
tab. – Tablet
top. – Topical
TB – Tuberculosis

Page | 3
 MEASUREMENTS
Notes on writing measurements:
• Quantities of 1 gram or more are written as 1 g, etc.
• Quantities less than 1 gram are written in milligrams (e.g., 500 mg, not
0.5 g).
• Quantities less than 1 milligram are written in micrograms (e.g., 100
micrograms, not 0.1 mg).
• When decimals are unavoidable, a zero is written before the decimal
point where there is no other figure (e.g., 0.5 mL and not .5 mL).
• The term milliliter (mL) is used and not cubic centimeter or cc.

Household Measures*
1 glassful = 250 mL
1 teacupful = 180 mL
1 tablespoonful (tbsp) = 15 mL
1 teaspoonful (tsp) = 5 mL
½ tsp = 2.5 mL

Some Practical Conversions

LENGTH 1 gallon (gal) = 3,785 mL
1 meter = 39.37 1 gal = 128 oz
inches
1 inch = 2.54 cm WEIGHT
1g = 15.432 gr
VOLUME 1 kilogram (kg) = 2.2 lb
1 mL = 16.23 (avoir)
minims 1 grain (gr) = 64.8 mg
1 mL = 20 drops 1 ounce (oz) (avoir) = 28.35 g
(gtt) 1 oz (apoth) = 31.1 g
1 minim = 0.06 mL 1 pound (lb) (avoir) = 454 g
1 fluid (f3) = 3.69 mL 1 lb (apoth) = 373.2 g
1 fluid ounce (foz) = 29.57 mL 1 oz (avoir) = 437.5 gr
1 pint (pt) = 473 mL 1 oz (apoth) = 480 gr

*Household measures stated in this Formulary may not be equal to the household utensils.
These utensils are usually LESS in volume as compared with standard measures.

Page | 4
 DRUGS AND CYP ENZYMES
Many drug interactions have resulted from the ability of one drug to
stimulate the metabolism of another, most often by increasing the activity of
hepatic enzymes that are involved in the metabolism of numerous therapeutic
agents. The increased activity is probably due to enhanced enzyme synthesis,
resulting in increased amounts of drug-metabolizing enzymes, an effect
frequently referred to as enzyme induction. Enzyme induction will usually result
in increased metabolism and excretion, and a reduced pharmacologic action of
the agent being metabolized by hepatic enzymes. Meanwhile, enzyme inhibition
will usually result in a decreased metabolism and excretion, and increased
activity of the agent being metabolized. This table serves only as a guide for
potential interactions. Other interactions not listed below may occur.

CYP1A2 inducers Pioglitazone

Omeprazole Rosiglitazone
Phenobarbital, Phenytoin CYP2C9 inducers
Tobacco smoking Rifampicin
CYP1A2 inhibitors St. John’s wort
Ciprofloxacin (moderate) CYP2C9 inhibitors
Verapamil (weak) Amiodarone (moderate)
CYP1A2 substrates Fluconazole (moderate),
Amitriptyline Fluoxetine
Clozapine Isoniazid
Haloperidol Ritonavir
Lidocaine CYP2C9 substrates
Olanzapine, Ondansetron Amitriptyline
Paracetamol, Propranolol Celecoxib
Theophylline Fluoxetine, Fluvastatin
Warfarin Glibenclamide, Gliclazide,
CYP2B6 inducers Glimepiride,
Phenobarbital, Phenytoin Glipizide
Rifampicin, Ritonavir Ibuprofen
CYP2B6 inhibitors Phenytoin
Clopidogrel Rosiglitazone, Rosuvastatin
CYP2B6 substrates Sulfamethoxazole
Clopidogrel Tamoxifen
CYP2C8 inducers Warfarin
Rifampicin CYP2C19 inducers
CYP2C8 inhibitors Carbamazepine
Gemfibrozil (strong) Rifampicin
Trimethoprim St. John’s wort
CYP2C8 substrates CYP2C19 inhibitors

Page | 5
 Clarithromycin CYP3A4/5 inducers
Fluoxetine Carbamazepine,
Ketoconazole Corticosteroids
Omeprazole (strong) Phenobarbital, Phenytoin
Topiramate Rifampicin, Ritonavir
CYP2C19 substrates St. John’s wort
Amitriptyline CYP3A4/5 inhibitors
Clomipramine, Clopidogrel Clarithromycin (strong)
Diazepam Danazol, Diltiazem (moderate)
Imipramine Erythromycin (moderate)
Lansoprazole Fluconazole (moderate)
Omeprazole Grapefruit juice (moderate)
Pantoprazole, Phenobarbital, Ketoconazole (strong)
Phenytoin Ritonavir (strong)
Propranolol Saquinavir (strong)
Warfarin Verapamil (moderate)
CYP2D6 inhibitors CYP3A4/5/7 substrates
Amiodarone (weak) Alfentanil, Alprazolam,
Celecoxib, Chlorphenamine, Amiodarone,
Clomipramine Amitriptyline, Amlodipine,
Fluoxetine (strong) Atorvastatin
Haloperidol Buspirone, Budesonide
Paroxetine (strong) Carbamazepine,
Quinidine Chlorphenamine,
Ritonavir Clarithromycin, Cocaine,
CYP2D6 substrates Codeine,
Amitriptyline Colchicine
Carvedilol, Chlorpromazine, Dexamethasone, Diazepam,
Clomipramine, Clozapine, Diltiazem
Codeine Ergot alkaloids, Erythromycin,
Dextromethorphan Ethinylestradiol, Etoposide,
Fluoxetine Etoricoxib
Haloperidol Felodipine, Fentanyl,
Lidocaine Fluticasone,
Metoclopramide, Metoprolol Fluvastatin
Olanzapine, Ondansetron, Haloperidol, Hydrocortisone
Oxycodone Ketoconazole
Propranolol Lidocaine
Risperidone Methylprednisolone,
Tamoxifen, Timolol, Tramadol Midazolam,
CYP2E1 inducers Mirtazapine
Alcohol Nifedipine, Nimodipine
Isoniazid Omeprazole, Ondansetron,
CYP2E1 substrates Oxycodone
Alcohol Propranolol
Paracetamol Quinidine, Quinine
Page | 6
 Risperidone, Ritonavir Carvedilol, Clarithromycin
Saquinavir, Sildenafil, Erythromycin
Simvastatin Ritonavir
Tamoxifen, Tramadol Verapamil
Verapamil, Vincristine P-glycoprotein substrates
Warfarin Carvedilol, Clopidogrel,
Zolpidem Colchicine
P-glycoprotein inducers Digoxin
Rifampicin Loperamide
St. John’s wort Paclitaxel
P-glycoprotein inhibitors Saquinavir
Amiodarone, Azithromycin

Page | 7
Table 1. Drugs with anticholinergic effects
Drugs with anticholinergic effects
Amantadine, Amitriptyline, Atropine
Belladonna alkaloids, Benztropine, Biperiden, Brompheniramine
Chlorpheniramine, Chlorpromazine
Diphenhydramine
Hyoscine (butylbromide or hydrobromide)
Ipratropium (nebulized)

Table 2. Drugs that may prolong QT interval

Class Drug/s
Antiarrhythmics Amiodarone, Disopyramide, Sotalol
Antipsychotics Haloperidol
Anti-infectives Azithromycin, Chloroquine, Clarithromycin, Erythromycin,
Fluconazole, Moxifloxacin, Quinine
Miscellaneous Cocaine, Tricyclic Antidepressants

Table 3. Drugs that may cause seizures

Drugs that may cause seizures
Antipsychotics
Chloroquine
Ertapenem
Imipenem, Isoniazid
MAO Inhibitors, Mirtazapine, Moxifloxacin
Neostigmine, Norfloxacin
Pizotifen, Promethazine, Pyridostigmine, Pyrimethamine
Rivastigmine
Selective Serotonin Reuptake Inhibitors
Tricyclic Antidepressants, Theophylline

Table 4. Drugs which reduce blood pressure

Drugs which reduce blood pressure
Alcohol, Amlodipine, Atenolol
Chlorpromazine, Olanzapine, Risperidone
Diazepam
Captopril, Enalapril
Clonidine
Diltiazem
Furosemide
Hydralazine, Hydrochlorothiazide
Isosorbide dinitrate
Losartan
Methyldopa
Nifedipine
Metoprolol, Propranolol
Sodium Nitroprusside
Page | 8
 Spironolactone
Timolol
Verapamil

Table 5. Drugs that may add to serotonin toxicity

Class Drugs
Antidepressants St. John’s wort, MAO inhibitors (including
moclobemide), SSRIs, TCAs
Opioids Dextromethorphan, Fentanyl, Pethidine
Stimulants Hallucinogenic Amphetamines, Phentermine
Others Illicit drugs (e.g., ‘ecstasy’, LSD, cocaine),
Selegiline,
Linezolid, Lithium

Page | 9
ALIMENTARY TRACT AND METABOLISM
ALIMENTARY TRACT AND
METABOLISM
DRUGS FOR ACID RELATED
DISORDERS
ANTACIDS
IMMUNE SYST
ALUMINUM HYDROXIDE
Rx + MAGNESIUM
Oral: 225 mg aluminum hydroxide + 200 mg
magnesium hydroxide, per 5 mL
suspension, 120 mL
A non-systemic antacid that combines
aluminum hydroxide and magnesium
hydroxide to reduce the effect on
bowel movement, and is used for the
relief of epigastric pain from peptic
ulcers through acid neutralization.
Indications: Symptomatic relief of symptoms
related to hyperacidity from
heartburn, hiatal hernia, upset
stomach, peptic ulcer, peptic
esophagitis, or gastritis.
Contraindications: Severe renal impairment;
hypophosphatemia; undiagnosed GI
and rectal bleeding; porphyria;
appendicitis.
Dose:
Hyperacidity, by mouth, ADULT, 10-20 mL 4
times daily (maximum, 80 mL daily).
Dose Adjustments:
Renal Impairment: Use with caution due to the
risk of accumulation and toxicity. For
mild-to-moderate renal impairment,
dose reduction is warranted. For severe
Page | 10
impairment, avoid use and refer the
patient to a specialist.
Precautions:
WARNING: Aluminum and magnesium salts
may be hazardous in patients with renal
insufficiency. If intensive antacid therapy is
to be used, only non-systemic
(nonabsorbable) antacids should be
considered because of the potential danger
of alkalosis with systemic therapy.
Acute porphyria; prolonged antacid therapy
may result in hypophosphatemia (Al in
antacid may form insoluble complexes
with phosphate leading to decreased
phosphate absorption in the GI tract);
dehydration; fluid restriction; constipation
(may be exacerbated by antacids
containing Al); diarrhea (may be
exacerbated by antacids containing Mg);
hepatic impairment; renal impairment
especially in elderly and children (severe:
aluminum is absorbed and may
accumulate); GI disorders associated with
decreased bowel motility or obstruction;
some products may contain
phenylalanine.
Elderly (may be predisposed to diarrhea or
constipation); children.
Adverse Drug Reactions:
Common: Constipation, diarrhea, GI irritation
Less Common: Chalky taste, fecal
discoloration, hypophosphatemia,
nausea, vomiting.
Rare: Anemia, encephalopathy, fecal
impaction, hypermagnesemia,
hypophosphatemia, intestinal
obstruction, osteomalacia, proximal
myopathy.
Drug Interactions:
NOTE: Antacids should preferably not be taken
at the same time as other oral drugs since
they may impair absorption (interactions
ALIMENTARY TRACT AND METABOLISM
may be avoided by having an interval of at
least 2 hours between taking an antacid
and the other drug).
Monitor closely with:
Acetylsalicylic acid – its excretion is increased
by alkaline urine (produced by the
antacid).
Azithromycin – reduced azithromycin
absorption.
Chloroquine – reduced chloroquine
absorption.
Digoxin – possibly reduced digoxin absorption.
Enalapril – reduced enalapril absorption.
Isoniazid – reduced isoniazid absorption.
Rifampicin – reduced rifampicin absorption.
Avoid concomitant use with:
Bisphosphonates – antacids significantly
reduce the absorption of oral
bisphosphonates, and may reduce their
activity (do not take within 2 hours of
taking a bisphosphonate).
Iron – antacids may decrease iron absorption
(separate administration times as long as
possible).
Ketoconazole – antacids reduce the
absorption of ketoconazole by increasing
gastric pH, possibly decreasing the
antifungal effect (give at least 2 hours
apart).
Quinolones – antacids bind to quinolones in
the GIT, reducing their absorption and
activity (give quinolone at least 2 hours
before, or 4-6 hours after the antacid).
Rosuvastatin – antacids may decrease the
concentration of rosuvastatin (give the
antacid 2 hours after rosuvastatin).
Tetracyclines (e.g. doxycycline) – antacids form
poorly-soluble chelates with tetracyclines,
reducing their absorption and anti-
infective activity.
Administration: Shake well before use; best
given 1-3 hours after the last principal
meal to neutralize the acid produced in
response to the meal, and provide
buffering when the food has already left
the stomach.
Pregnancy Category: B
ATC Code: A02AD01
FOR PEPTIC ULCER AND
GASTROESOPHAGEAL REFLUX DISEASE
(GERD)
Proton Pump InhibitorsSYST
OMEPRAZOLE
Rx
Oral: 20 mg and 40 mg capsule
A benzimidazole, which acts as a proton pump
inhibitor (PPI), by blocking the final step of
acid production. It acts by inhibiting the
H+/K+–ATPase system at the parietal
cells of the stomach, suppressing both
basal, and stimulated gastric acid
secretion.
Indications: Duodenal ulcer, gastric ulcer, and
NSAID-associated gastric and duodenal
ulcers and erosions; H. pylori eradication
in peptic ulcer disease; symptomatic
GERD; reflux esophagitis; acid-related
dyspepsia.
Contraindications: Known hypersensitivity to
omeprazole and other proton pump
inhibitors, or any component of the
formulation.
Dose:
Duodenal ulcer, by mouth, ADULT, 20-40 mg
daily for at least 4 weeks; CHILD >20
kg, 20 mg daily; CHILD 10-20 kg, 10 mg
daily; CHILD 5- 10 kg, 5 mg daily.
Erosive esophagitis, by mouth, ADULT, 20-40
mg for at least 4 weeks. Maintenance:
20 mg daily for up to one year; CHILD
>20 kg, 20 mg daily; CHILD 10-20 kg,
10 mg daily; CHILD, 5-10 kg, 5 mg daily.
Helicobacter pylori infection, by mouth, ADULT,
40 mg every 12 hours for 10 days, with
Page | 11
ALIMENTARY TRACT AND METABOLISM
amoxicillin (if non-penicillin allergic) at Surgery (treatment should be continued
1 g every 12 hours, and clarithromycin perioperatively).
at 500 mg every 12 hours for 10-14 Pregnancy (use only if really warranted);
days; CHILD >20 kg, 20 mg daily; CHILD breastfeeding (omeprazole is excreted
10-20 kg, 10 mg daily; CHILD 5-10 kg, in breast milk, but is not likely to
5 mg daily. influence the infant when therapeutic
Note: For more information on the doses are used).
treatment of H. pylori infection in Adverse Drug Reactions:
peptic-ulcer disease, please see
Clarithromycin in Anti-infectives Common: Abdominal pain, constipation,
Section. diarrhea, flatulence, headache,
Gastric ulcer, by mouth, ADULT, 20 - 40 mg nausea, vomiting
daily for at least 4 - 8 weeks; CHILD >20
kg, 20 mg daily; CHILD 10-20 kg, 10 mg Less Common: Decreased absorption of
daily; CHILD, 5-10 kg, 5 mg daily. vitamin B12, dizziness, drowsiness, dry
GERD, by mouth, ADULT, 20-40 mg daily for 4- mouth, fatigue, insomnia, malaise,
8 weeks; CHILD > 20 kg, 20 mg daily; paresthesia, pruritus, rash,
CHILD 10-20 kg, 10 mg daily; CHILD, 5- somnolence, urticarial, vertigo
10 kg, 5 mg daily.
Hypersecretory condition (e.g., Zollinger-Ellison Rare: Alopecia, arthralgia, blurred vision,
Syndrome), by mouth, ADULT, 60 mg confusion, dermatitis, gynecomastia,
daily (initial) up to 360 mg/day divided hemolytic anemia, hepatitis,
every 8 hours. If dose >80 mg, divide it. hypersensitivity reactions, hypomag-
nesemia, interstitial nephritis, jaundice,
Dose Adjustments: leukopenia, microscopic colitis,
Hepatic Impairment: For mild-to-moderate myalgia, myopathy pancreatitis,
hepatic impairment, dose reduction is peripheral edema, raised liver
warranted; for severe impairment, the enzymes, skin reactions, taste
patient should be referred to a disturbance, thrombocytopenia
specialist.
Drug Interactions:
Precautions: NOTE: CYP-based interactions: omeprazole (a
Gastric malignancy (relief of symptoms does CYP1A2 inducer and a CYP2C19 inhibitor)
not preclude the presence of a gastric may alter both the therapeutic and
malignancy); GI infection (use of PPI adverse effects of drugs that are primarily
may increase risk of infections); metabolized by CYP enzymes
fractures (increased incidence of
osteoporosis-related bone fractures of Monitor closely with:
the hip, spine, or wrist may occur);
hypomagnesemia (rarely reported); Anticoagulants (e.g., warfarin) – enhanced
gastric carcinoma (exclude before effect.
starting treatment for gastric ulcers - Anti-epileptic agents – enhanced effect.
PPI may mask symptoms and delay Azoles (e.g., ketoconazole) – their absorption is
diagnosis); reduced by omeprazole, thus decreasing
Hepatic impairment (risk of accumulation the antifungal effect.
when higher doses are used; monitor Benzodiazepines (e.g., diazepam and
for adverse effects); severe liver midazolam) – their concentration may be
disease; increased by omeprazole, possibly
enhancing the effect.

Page | 12
ALIMENTARY TRACT AND METABOLISM
Clopidogrel – its antiplatelet activity may be
reduced by omeprazole by reducing the
formation of its active metabolite.
Clozapine – its concentration may be
decreased by omeprazole, possibly
affecting its effect.
Digoxin – enhanced effect.
Fluconazole – this approximately doubles the
concentration of omeprazole.
Iron Salts – their absorption may be reduced
by omeprazole.
Mycophenolate – omeprazole may decrease
its absorption (due to increased gastric
pH) with possible loss of efficacy.
Saquinavir – its concentration may be
increased by omeprazole, possibly
increasing the risk of toxicity.
St. John’s wort – this may increase the
metabolism of omeprazole, possibly
decreasing its concentration and clinical
effect.
Administration: To be taken 30 minutes before
a meal; preferably at breakfast if to be
taken once a day.
NOTE: For patients with swallowing difficulties,
capsules can be opened, and the
contents swallowed or suspended in a
slightly acidic fluid, e.g., fruit juice or in
noncarbonated water. The suspension
must be drunk within 30 minutes.
Alternatively, these patients can suck the
capsule and swallow the contents. The
contents of the capsule should neither be
chewed nor crushed.
Dose Adjustment:
Geriatric: Consider dose adjustment
Pregnancy Category: C
ATC Code: A02BC01
DRUGS FOR FUNCTIONAL
GASTROINTESTINAL
DISORDERS
AMOXICILLIN
Rx
Oral: 250 mg and 500 mg capsule (as
trihydrate)
100 mg/mL granules/powder for
drops
(suspension), 15 mL (as
trihydrate)
250 mg/5 mL granules/powder for
suspension, 60 mL (as trihydrate)
A penicillinase-susceptible aminopenicillin
having an extended spectrum of activity;
oral absorption is not impaired by food,
and is more rapidly and completely
absorbed, with a higher bioavailability
and less GI irritation than ampicillin.
Indications: For Helicobacter pylori eradication
(as combination therapy - see under
Clarithromycin in Anti-Infectives Section
for the Eradication of H. pylori Infection in
Peptic Ulcer Disease).
See Amoxicillin under Beta-Lactam
Antibacterials, Penicillins in the Anti-
Infectives Section for other indications
and more information.
CLARITHROMYCIN
Rx
Oral: 250 mg and 500 mg base tablet
125 mg/5 mL and 250 mg/5 mL
granules/ powder for suspension, 50
mL
An erythromycin-derived, macrolide antibiotic,
which can be used in regimens for
Page | 13
ALIMENTARY TRACT AND METABOLISM
Helicobacter pylori eradication, and low- A naturally occurring tertiary amine anti-
risk CAP when indicated. muscarinic alkaloid from Atropa
Indications: For Helicobacter pylori eradication belladonna that competitively blocks
(as combination therapy - see under acetylcholine action in central and
Clarithromycin for the Eradication of H. peripheral muscarinic autonomic
Pylori Infection in Peptic Ulcer Disease in receptors.
the Anti-Infectives Section).
Indications: Treatment of functional
disturbances of gastrointestinal motility
See Clarithromycin under Macrolides in the such as irritable bowel syndrome.
Anti-Infectives Section for other
indications and more therapeutic NOTE: Has limited efficacy as an anti-
information. muscarinic and should be used only if
other measures (e.g., diet, sedation,
counseling, amelioration of
environmental factors) have been of little
METRONIDAZOLE or no benefit.
Rx
Contraindications: Angle-closure glaucoma;
Oral: 250 mg and 500 mg base tablet severe inflammatory GI disease or GI
125 mg base/5 mL (200 mg/5 mL as obstruction; prostatic hypertrophy;
benzoate) suspension, 60 mL prostatism and urinary obstruction;
myasthenia gravis; thyrotoxicosis;
A nitroimidazole, an antiprotozoal drug, which organochlorine poisoning; pyloric
has potent antibacterial activity against
stenosis; poisoning caused by CNS
anaerobes, including Bacteroides and
adrenergic stimulants, phenothiazines,
Clostridium spp.
tricyclic antidepressants; and, other
Indications: For Helicobacter pylori eradication anticholinergics.
(as combination therapy - see under
Clarithromycin for the Eradication of H. Dose:
pylori Infection in Peptic Ulcer Disease, in Diverticular disease, irritable bowel syndrome,
the Anti-Infectives Section). non-ulcer dyspepsia, by mouth, ADULT,
0.6–1.2 mg as a single dose at
See Metronidazole under Imidazole derivatives bedtime.
in the Anti-Infectives Section for other
indications and more therapeutic Dose Adjustment:
information. Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction, or less frequent doses, after
ANTICHOLINERGICS initial atropinization, is warranted
(since atropine may be eliminated more
slowly).
ATROPINE For severe impairment, the patient should be
Rx referred to a specialist.

Precautions:
Oral: 600 micrograms (equiv. to 500 mcg Children; elderly;
atropine) tablet GI disorders (see contraindication); Down
syndrome; prostatic enlargement;

Page | 14
ALIMENTARY TRACT AND METABOLISM
cardiac disorders; hypoxia;
constipation, delirium, tachycardia and
fever from any cause (all these may be
worsened by atropine); pyrexia and in
warm environments (monitor
temperature and keep patients cool).
Pregnancy (crosses the placenta and may
cause tachycardia); breastfeeding
(small amount present in milk - may
cause antimuscarinic effects in
infants).
NOTE: Since atropine has a short duration, late
unopposed bradycardia may result.
Therefore, close monitoring is
necessary
Adverse Drug Reactions:
NOTE: Adverse effects following single or
repeated doses of atropine are most
often the result of excessive dosage.
Common: Blurred vision, constipation,
cycloplegia, delirium, dryness of mouth,
nose and skin, difficulty in micturition
and swallowing, fever, flushing,
mydriasis, palpitations, photophobia,
thirst, transient bradycardia followed by
tachycardia, urinary retention.
Less Common: Agitation, arrhythmias, ataxia,
confusion (in elderly), disorientation,
excitement, headache, heat
prostration, hyperpyrexia,
hypertension, paralytic ileus, psychosis,
rapid respiration, rash, restlessness,
vomiting.
Rare: Angle-closure glaucoma, myocardial
infarction, seizures.
Drug Interactions:
Monitor closely with:
Alcohol – enhanced CNS effects/CNS
depression.
Antacids – these may delay or reduce oral
absorption of atropine.
Beta blockers (e.g., metoprolol) – their
retention time may be increased by
atropine; it may also enhance their
dissolution and bioavailability.
Chlorpromazine – increased antimuscarinic
adverse effects (but reduced plasma
chlorpromazine concentration).
Nitrates (e.g., isosorbide dinitrate) – atropine
may reduce the effects of sublingual
tablets (failure to dissolve under the
tongue due to dry mouth).
Avoid concomitant use with:
Anticholinergic drugs or other drugs with
anticholinergic effects – these increase
the therapeutic effect and risk of
adverse effects of atropine (including
central anticholinergic delirium); avoid
these combinations if possible (if
required, monitor the patient, and
reduce dose if necessary).
Anticholinesterases (e.g., neostigmine,
pyridostigmine) – combining
anticholinergics with these drugs,
which increase acetylcholine
concentration, will antagonize the
anticholinergic effect.
Digoxin – atropine may increase serum digoxin
levels, resulting in enhanced actions
and risk of toxicity.
Haloperidol – schizophrenic symptoms may
worsen due to decreased plasma
concentration of haloperidol.
Metoclopramide – atropine antagonizes the
effects of metoclopramide on GI
activity.
Norepinephrine – enhanced pressor effect; its
reflex bradycardia is blocked by
atropine.
Phenylephrine – atropine increases the risk of
severe hypertension with
phenylephrine eye drops (use the
combination cautiously and monitor
BP).
Administration:
For oral administration, may be taken with or
without food.
For IV administration, administer undiluted by
rapid IV injection.
Page | 15
ALIMENTARY TRACT AND METABOLISM
Pregnancy Category: C
ATC Code: A03BA01
ANTISPASMODICS
DICYCLOVERINE
Rx
Oral: 10 mg tablet (as hydrochloride)
10 mg/5 mL syrup, 60 mL
hydrochloride)
An antimuscarinic agent used primarily as
antispasmodic. It has a much less
marked antimuscarinic action than
atropine and may also have some direct
action on smooth muscle.
Indications: Treatment of patients with
functional bowel or irritable bowel
syndrome; adjunct in GI disorders
characterized as functional
disturbances of gastrointestinal
motility.
Contraindications: Obstructive diseases of the
GI tract; severe ulcerative colitis; reflux
esophagitis; unstable cardiovascular
status in acute hemorrhage;
obstructive uropathy; glaucoma;
myasthenia gravis; breastfeeding;
infants.
Dose:
Gastrointestinal motility disorders/irritable
bowel, by mouth, ADULT, 20 mg 4 times
daily for 7 days; after 1 week, may
increase to 40 mg 4 times daily; CHILD
6-24 months, 5 mg per dose 3-4 times
daily; CHILD 2-12 years, 10 mg per
dose 3-4 times daily.
NOTE: In adults, if doses < 80 mg daily do not
achieve desired results, or if adverse
effects occur, discontinue therapy.
Page | 16
Safety data are not available for doses
>80 mg daily for a duration of >2
weeks.
Dose Adjustments:
Geriatric:
Refer to adult dosing. Use with caution; lower
dosages may be warranted.
Renal Impairment: No dosage adjustment
provided in the manufacturer’s labeling
(has not been studied); use with
caution.
Hepatic Impairment: No dosage adjustment
provided in the manufacturer’s labeling
(as
(has not been studied); use with
caution.
Precautions:
WARNING: Should not be given to children
below 6 months of age
Avoid performing tasks that require mental
alertness (e.g., operating machinery or
driving since dicycloverine may cause
drowsiness and/or blurred vision);
discontinue if diarrhea occurs since this
may be a sign of incomplete intestinal
obstruction; during hot weather and/or
exercise (due to the possible
occurrence of heat prostration).
Psychosis and delirium have been reported in
patients with an extreme sensitivity to
anticholinergic effects or at excessive
dosages, such as the elderly or patients
with mental illness.
Elderly (avoid long-term use due to intolerable
anticholinergic effects and uncertain
effectiveness – the potential risk for a
toxic reaction is greater than the
potential benefit).
Infants (serious respiratory reactions, central
nervous system symptoms, and deaths
have been reported)
Adverse Drug Reactions:
Common: Dizziness, xerostomia, nausea,
blurred vision, somnolence,
nervousness, weakness.
ALIMENTARY TRACT AND METABOLISM
Rare: Abdominal distension, abdominal pain,
anaphylactic shock, angioedema, Indications: Smooth muscle spasm of the
confusional state, constipation, genitourinary or GI tract (e.g., renal and
cycloplegia, delirium, dermatitis biliary spasm).
(allergic), hypersensitivity, dyspepsia,
dyspnea, erythema, facial edema, Contraindications: Hypersensitivity to hyoscine
fatigue, hallucinations, headache, or any component of the formulation;
insomnia, lactation suppressed, glaucoma; megacolon, myasthenia
malaise, mydriasis, nasal congestion, gravis; stenotic lesions of the GI tract;
palpitation, rash, syncope, paralytic ileus; acute hemorrhage;
tachyarrhythmias, vomiting. tachycardia, angina, or heart failure;
obstructive prostatic hypertrophy; IM
Drug Interactions: administration in patients with
Monitor closely with: anticoagulant therapy.
Analgesics (Opioid) – their adverse effects may
be enhanced by dicycloverine, Dose:
specifically the risk for constipation and Acute therapy of smooth muscle spasm, by
urinary retention. mouth, ADULT, 10-20 mg daily;
Anticholinergic Agents – dicycloverine may
enhance the adverse effect of other For prolonged therapy, by mouth,
anticholinergics. ADULT, 10 mg 3-5 times daily
Thiazide Diuretics – their serum concentration (maximum, 60 mg daily); by IM, IV or SC
may be increased by dicycloverine. injection, 10-20 mg (maximum, 100
mg/day); CHILD >6 years, 10 mg 3
Avoid concomitant use with: times daily.
Ipratropium (Oral Inhalation) – this may
enhance the anticholinergic effect of NOTE: Doses can be repeated after 30 minutes
anticholinergic agents. if needed (may need to be repeated
more frequently in endoscopy).
Administration: Maybe taken before or after
meals. Dose Adjustments:
Renal Impairment:
Pregnancy Category: B For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist. This is not
HYOSCINE recommended in patients with renal
Rx (AS N-BUTYLBROMIDE)
failure.

Precautions:
Oral: 10 mg tablet WARNING: Patients who experience
blurred vision or drowsiness must not
5 mg/5 mL syrup, 60 mL
drive or operate machinery
Inj.: 20 mg/mL, 1 mL ampul (IM, IV, SC)

A poorly-absorbed, quaternary amine, CNS effects (may cause drowsiness and

anticholinergic agent that is used to blurred vision, caution in performing
relax smooth muscles, and reduce GI tasks which require mental alertness);
motility and spasm idiosyncratic reactions (though these

Page | 17
ALIMENTARY TRACT AND METABOLISM
are rare, patients may experience acute
toxic psychosis, agitation, confusion,
delusions, hallucinations, paranoid
behavior, and rambling speech); visual
disturbances (discontinue if the patient
reports unusual visual disturbances or
pain within the eye); withdrawal
(adverse events, including dizziness,
headache, nausea, vomiting, may occur
following abrupt discontinuation of
large doses or in patients with
Parkinson’s disease); dementia
(anticholinergics may worsen
symptoms and antagonize therapeutic
effects of anticholinesterases);
Fever, high ambient temperature (risk of
hyperthermia);
Cardiovascular disease; GI obstruction or
atony; genitourinary disease and
obstruction; glaucoma; hiatal hernia;
hyperthyroidism; psychosis; seizure
disorders; ulcerative colitis; renal and
hepatic impairment;
Elderly (avoid use due to potent anticholinergic
adverse effects and uncertain
effectiveness); and children (increased
risk of adverse effects);
Anaphylaxis.
Adverse Drug Reactions:
Less common: Diarrhea, dry mouth, nose,
throat or skin, dyshidrosis, headache,
increased eye pressure, itching,
mydriasis, nausea, skin reactions (e.g.,
urticaria, pruritus, erythema, rash),
tachycardia, vomiting.
Rare: Acute toxic psychosis, angioedema,
decreased blood pressure, blurred
vision, coma, confusion, constipation,
dizziness, drowsiness, dysuria, fixed
drug eruptions, flushing,
hypersensitivity reactions including
anaphylaxis; orthostatic hypotension,
palpitations, rapid and irregular pulse,
swallowing difficulties, tremor, urinary
retention.
Page | 18
Drug Interactions:
Monitor closely with:
Alcohol – enhanced CNS depressant effect.
Topiramate and zonisamide – anticholinergics
may decrease sweating, and cause
hyperthermia; risk is increased when
given with these drugs.
Avoid concomitant use with:
Anticholinergic drugs – additive anticholinergic
effects; may increase the therapeutic
and adverse effects.
Anticholinesterases – these can antagonize
the anticholinergic effect of hyoscine.
Administration: Swallow tablets whole with a
full glass of water.
Pregnancy Category: C
ANTI-EMETICS AND
ANTINAUSEANTS
SEROTONIN (5HTs) ANTAGONISTS
METOCLOPRAMIDE
Rx
Oral: 10 mg tablet (as hydrochloride)
5 mg/5 mL syrup (as base and as
hydrochloride), 60 mL
A dopamine (D2) antagonist that blocks
receptors in the chemoreceptor trigger
zone of the medulla, resulting in potent
anti-nausea and antiemetic action; also
blocks receptors in the GI tract,
stimulating gastric emptying and small
intestinal transit.
Indications: Management of nausea and
vomiting in GI disorders, in migraine, and
in chemotherapy and radiotherapy;
disorders of decreased gastrointestinal
ALIMENTARY TRACT AND METABOLISM
motility such as gastroparesis or ileus;
Gastroesophageal Reflux Disease
(GERD).
NOTE: In children and adolescents <20 years
of age, use is restricted to the treatment
of severe intractable vomiting of known
etiology, as an aid to GI intubation,
management of radiotherapy and
chemotherapy-induced nausea and
vomiting, and as premedication.
Contraindications: Pheochromocytoma; GI
obstruction; 3 to 4 days after GI surgery;
perforation or hemorrhage; convulsive
disorders.
Dose:
Nausea and vomiting, GERD, gastroparesis, by
mouth, ADULT, 10 mg 3 times daily;
YOUNG ADULT 15–19 years (under 60
kg), 5 mg 3 times daily; CHILD 9–14
years (30 kg and over), 5 mg 3 times
daily; CHILD 5–9 years (20 to 29 kg),
2.5 mg 3 times daily; CHILD 3–5 years
(15–19 kg), 2 mg 2–3 times daily;
CHILD 1–3 years (10–14 kg), 1 mg 2–
3 times daily; INFANT <1 year (or up to
10 kg), 1 mg twice daily; (usual
maximum of 500 mcg/kg daily,
particularly for children and young
adults)
NOTE: High-dose use in cytotoxic chemotherapy is
reserved for patients at a high risk of emesis
or when other therapies are ineffective.
Dose Adjustments:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted.
For severe impairment, refer the patient to a
specialist.
Precautions:
WARNING: Can cause tardive dyskinesia
(TD). Avoid treatment >12 weeks unless the
therapeutic benefit is thought to outweigh
the risk of developing TD.
For short-term use only, i.e., <12 weeks
(increased risk for tardive dyskinesia with
cumulative dose and length of treatment);
Edematous conditions (use in caution in
patients who are at risk of fluid overload;
may cause a transient increase in serum
aldosterone); Depression; Parkinson’s
disease (avoid its use if possible as
symptoms may worsen; may have
increased risk of Extrapyramidal
Syndrome or EPS); epilepsy; hypertension;
porphyria; severe renal impairment;
In the elderly (more sensitive to adverse
effects; avoid high doses and prolonged
use); young adults and children (avoid
high doses; increased risk of EPS,
particularly acute dystonia);
May mask underlying disorders, such as
cerebral irritation; avoid for 3–4 days after
GI surgery;
Pregnancy (not known to be harmful);
breastfeeding (present in milk; adverse
effects possible, thus monitor infants for
adverse effects).
NOTE: May impair the mental and/or physical
abilities required for the performance of
hazardous tasks, such as operating
machinery or driving a motor vehicle.
Adverse Drug Reactions:
Common: Akathisia, dizziness, drowsiness,
fatigue, headache, somnolence.
Less common: Bronchospasm, constipation,
depression, diarrhea, edema,
Extrapyramidal Syndrome (EPS),
hyperprolactinemia leading to
galactorrhea, hypertension, hypotension,
pruritus, rash, restlessness, urticaria.
Rare: Abnormalities in cardiac conduction (IV
form), acute congestive heart failure,
agranulocytosis, bradycardia, fluid
retention, hyperaldosteronism,
leukopenia, methemoglobinemia,
neuroleptic malignant syndrome,
neutropenia, porphyria, supraventricular
tachycardia.
Drug Interactions:
Page | 19
ALIMENTARY TRACT AND METABOLISM
Monitor closely with:
Alcohol – metoclopramide may increase the
CNS depressant effects of alcohol (may
also accelerate gastric emptying of
alcohol, possibly increasing its rate and
extent of absorption).
Analgesics (e.g., aspirin and paracetamol) –
their effect is enhanced by
metoclopramide due to increased
absorption.
Digoxin – its absorption may be decreased by
metoclopramide from the stomach.
Avoid concomitant use with:
Extrapyramidal reactions-causing drugs (e.g.,
chlorpromazine, fluphenazine, and
haloperidol) may increase the frequency
and severity of extrapyramidal symptoms.
Opioid-containing medications – antagonism
of metoclopramide effect on GI activity
Administration: Give IV injection over 1-2
minutes to lessen transient agitation and
restlessness.
Pregnancy Category: B
LAXATIVES
DRUGS FOR CONSTIPATION
OTC BISACODYL
Oral: 5 mg tablet
5 mg MR tablet
Rectal: 5 mg suppository (for children)
10 mg suppository (for adults)
A diphenylmethane stimulant laxative that acts
by stimulating peristalsis by directly
irritating the smooth muscle of the large
intestine. It also alters water and
electrolyte secretion, producing net
Page | 20
interstitial fluid accumulation and
laxation.
Indications: Management of constipation.
Contraindications: Acute abdominal conditions
(e.g. appendicitis, intestinal inflammatory
bowel disease); intestinal obstruction;
ileus; severe dehydration; severe
abdominal pain associated w/ nausea
and vomiting; anal fissures or ulcerative
colitis w/ mucosal damage (rectal).
Dose:
Management of constipation, by mouth,
ADULT, 5–10 mg at night, up to 20 mg
may be given as necessary; CHILD 4 to 10
years, 5 mg at night.
per rectum, ADULT, 10 mg in the morning;
CHILD ≤10 years, 5 mg in the morning
Precautions:
Intestinal obstruction or acute abdominal
conditions such as appendicitis;
inflammatory bowel disease; severe
dehydration; anal fissures, proctitis,
ulcerated hemorrhoids (avoid the use of
suppositories).
Adverse Drug Reactions:
Common: Abdominal discomfort, diarrhea,
electrolyte disturbance, nausea,
vertigo, vomiting, hematochezia.
Less common: Irritation, proctitis (rectal)
Rare: Hypersensitivity reactions
Drug Interactions: No information was found
Administration: To be taken on an empty
stomach.
For tablets, administer in the evening if a
bowel movement on the following
morning is desired. MR tablets must be
swallowed whole and not crushed or
chewed. Do NOT take within 1 hour of
antacids or milk.
For suppositories, administer at the time a
bowel movement is desired.
ALIMENTARY TRACT AND METABOLISM
Pregnancy Category: C
ATC Code: A06AB02
LACTULOSE
Rx
Oral: 3.3 g/5 mL (or 3.35 g/5 mL) syrup, 120
mL
A synthetic lactose derivative that can act as
an ammonia (NH3) detoxicant. It is
degraded by bacteria in the gut resulting
in an acidic pH, which inhibits NH3
diffusion into the blood while enhancing
the diffusion of NH3 from the blood into
the gut. It also produces an osmotic effect
in the colon with resultant distention,
promoting peristalsis and reducing blood
ammonia concentration to reduce the
degree of portal-systemic
encephalopathy.
Indications: Management of constipation;
prevention and treatment of hepatic
encephalopathy.
Contraindications: Patients requiring a low
galactose diet.
Dose:
Constipation, by mouth, ADULT, 10–20 g (15–
30 mL) daily, may be increased to 40 g
(60 mL) daily if necessary.
Portal Systemic Encephalopathy (PSE),
prevention, by mouth, ADULT, 20–30 g
(30–45 mL) 3–4 times daily (adjust dose
every 1–2 days to produce 2 to 3 soft
stools daily); CHILD, 26.7–60 g daily (40–
90 mL daily) in divided doses (adjust the
dosage to produce 2–3 stools daily);
INFANT, 1.7–6.7 g daily (2.5–10 mL daily)
in divided doses (adjust the dosage to
produce 2–3 stools daily).
Acute PSE, treatment, by mouth, ADULT, 20–
30 g (30–45 mL) every 1 hour to induce
rapid laxation, reduce to 20– 30 g (30–45
mL) 3–4 times daily after laxation is
achieved (titrate to produce 2–3 soft
stools/day).
Overt Hepatic Encephalopathy (OHE),
treatment, by mouth, ADULT, 20–30 g
16.7 g (25 mL) every 1 to 2 hours until at
least 2 soft or loose bowel movements are
produced daily (titrate to maintain 2–3
bowel movements daily).
Precautions:
Electrolyte imbalance (monitor periodically for
electrolyte imbalance when used >6
months or in patients predisposed to
electrolyte abnormalities);
Hepatic disease.
Diabetes (contains galactose and lactose; use
with caution).
Elderly (may predispose electrolyte imbalance;
more likely to show CNS signs of
dehydration and electrolyte loss; sorbitol
is equally effective as a laxative and less
expensive, however, sorbitol cannot be
substituted in the treatment of hepatic
encephalopathy ); infants - may develop
hyponatremia and dehydration).
Adverse Drug Reactions:
Common and less common: Dehydration,
hypernatremia, hypokalemia, abdominal
discomfort, abdominal distention,
belching, cramping, diarrhea, flatulence,
nausea, vomiting.
Rare: Lactic acidosis
Drug Interactions:
Monitor closely with:
Glutamine (ammonia-lowering effects) -
Reduces the therapeutic effect of Lactulose
Page | 21
ALIMENTARY TRACT AND METABOLISM
Administration:
May mix with fruit juice, water, or milk. When
administered via a gastric tube, dilute to
prevent induction of vomiting and the
possibility of aspiration pneumonia.
Pregnancy Category: B
ATC Code: A06AD11
and glucose that is widely used in treating
children with acute non-cholera diarrhea,
and in adults and children with cholera.
Indications: Replacement of fluid and
electrolyte losses in mild to moderate
dehydration due to acute diarrhea or
vomiting; replacement of continuing loss
from vomiting or diarrhea.

Contraindications: Severe dehydration; severe

and sustained vomiting; diarrhea; glucose
ANTIDIARRHEALS, malabsorption; to patients with difficulty
INTESTINAL in drinking.
ANTIINFLAMMATORY/
ANTIINFECTIVE AGENTS Dose:
Fluid and electrolyte loss in acute diarrhea, by
mouth, ADULT, 200-400 mL solution after
ORAL REHYDRATION SALT every loose bowel movement;
INFANT and CHILD, according to Plans A,
FORMULATIONS
B, or C.
(Refer also to Guidelines in the
Management of Dehydration and
ORAL REHYDRATION SALTS
Rx (ORS-75 Replacements)
Diarrheal Diseases for other important
and more complete information).

Oral: Plan A: No dehydration (in infants and

Composition: (WHO recommended)
Reduced osmolarity ORS in g/L:
Sodium chloride - 2.6 g
Trisodium citrate dehydrate - 2.9 g
Potassium chloride - 1.5 g
Glucose, anhydrous - 13.5 g
Total Weight - 20.5 g
Reduced osmolarity ORS Equivalent in
mmol/L:
Sodium - 75
Chloride - 65
Potassium - 20
Citrate - 10
Glucose, anhydrous - 75
Total osmolarity - 245
N.B. Reconstitute with clean potable water.
The unused reconstituted solution shall
be discarded after 24 hours.
Plan B: Moderate dehydration (in infants and
An oral rehydration salt formulation containing
reduced osmolar concentration of sodium
children).
Nutritional advice, increased fluid intake
(in the form of soup, rice, water and
yogurt, or even just water), and zinc
supplementation at home are usually
sufficient.
However, for infants aged <6 months who
have not yet started taking solids, oral
rehydration solution must be given
without any particular restrictions.
Mother’s milk or dried cow’s milk must be
given without any particular restrictions.
In the case of mixed breast-milk/formula
feeding, the contribution of breastfeeding
should be increased. Parents should be
informed about the circumstances, in
which they should seek further advice.
children).

Page | 22
ALIMENTARY TRACT AND METABOLISM
Whatever the child’s age, a 4-hour
treatment plan is used to avoid short-term
problems.
It is recommended that parents are
shown how to give approximately 75
mL/kg of oral rehydration solution (in
small amounts and at regular intervals)
over 4 hours.
Parents or caregivers must be observant
to see how the child copes at the
beginning of the treatment. A larger
amount of solution can be given if the
child continues to have frequent stools.
In the event of vomiting, rehydration must
be discontinued for 10 minutes and then
resumed at a slower rate. In young
children, breastfeeding should be
continued upon demand; older children
should receive milk and nutritious food as
normal after completing the 4 hours of
oral rehydration.
The child’s status must be reassessed
after 4 hours to decide on the most
appropriate subsequent treatment.
Zinc supplementation should begin as
soon as the child can eat and has
completed 4 hours of oral rehydration.
Oral rehydration solution should continue
to be offered once dehydration has been
controlled, for as long as the child
continues to have diarrhea.
Plan C: Severe dehydration (in infants and
children).
Hospitalization is necessary, but the most
urgent priority is to start rehydration.
• In the hospital (or elsewhere), if the
child can drink, oral rehydration solution
must be given pending, and even during
IV infusion (give 20 mL/kg ORS every hour
by mouth before infusion, then 5 mL/kg
every hour by mouth during IV
rehydration).
• For IV supplementation, it is
recommended that Lactated Ringer’s
solution, preferably D5LR (or, if this is
unavailable, normal saline solution or
0.9% sodium chloride solution) is
administered at a rate adapted to the
child’s age (infant under 12 months: 30
mL/kg over 1 hour then 70 mL/kg over 5
hours; child over 12 months: 30 ml/kg
over 30 minutes then 70 ml/kg over 2.5
hours).
• If the IV route is unavailable, a
nasogastric tube is also suitable for
administering oral rehydration solution at
a rate of 20 mL/kg every hour for 6 hours.
If the child vomits, the rate of
administration of the oral solution must
be reduced. Reassess the child's status
after 3 hours (6 hours for infants) and
continue treatment as appropriate with
plans A, B, or C.
Dose Adjustments:
Renal Impairment:
Care should be taken in dose selection.
Precautions:
Renal impairment (there is an increased risk of
adverse effects); severe dehydration
should be treated with IV electrolyte
solutions.
Adverse Drug Reactions:
Rare: Hypernatremia, vomiting
Drug Interactions: No information was found
Administration: Reconstitute it with clean
potable water. The unused
reconstituted solution shall be
discarded after 24 hours. It may be
taken with or without food
Pregnancy Category: C
ATC Code: A07CA
Page | 23
ALIMENTARY TRACT AND METABOLISM
Traveler’s diarrhea, by mouth, ADULT, initially
ANTIPROPULSIVES 4 mg after first loose stool, followed by 2
mg after each subsequent stool
(maximum, 8 mg daily); CHILD 9–11

OTC
LOPERAMIDE
Oral: 2 mg capsule (as hydrochloride)
A synthetic pethidine derivative that inhibits
gut motility and may also reduce
gastrointestinal secretions. It acts directly
on circular and longitudinal muscles
through the opioid receptor to inhibit
peristalsis and prolong transit time.
Indications: Inhibition of gut motility for the
reduction of gastrointestinal secretion;
symptomatic control of acute and chronic
non-specific diarrhea; adjunct to fluid
electrolytes replacement in the
management of acute and chronic non-
specific diarrhea.
Contraindications: Hypersensitivity to
loperamide or any component of the
formulation; abdominal pain without
diarrhea; children <2 years.
years, 2 mg after first loose stool, followed
by 1 mg after each subsequent stool
(maximum dose, 6 mg daily); CHILD 6– 8
years, 2 mg after first loose stool, followed
by 1 mg after each subsequent stool
(maximum dose, 4 mg daily).
NOTE: NOT recommended for infants and
children < 2 years of age.
Precautions:
WARNING: If diarrhea lasts longer than 2
days, symptoms worsen, or abdominal
swelling or bulging develops, discontinue
use and consult a healthcare provider.
Ileus and constipation; abdominal distension;
Acute inflammatory bowel disease;
Antibiotic-associated colitis;
Dysentery;
Hepatic impairment;
Children;
NOT recommended for infants and children <
2 years of age
Pregnancy.

Dose:
Adverse Drug Reactions:
Acute diarrhea, by mouth, ADULT, initially 4 mg,
Common: Dizziness, constipation, abdominal
followed by 2 mg after each loose stool
cramping, nausea.
(maximum, 16 mg daily, the usual dose is
Less common: Abdominal distention,
6-8 mg); CHILD 8–12 years (>30 kg), 2 mg
abdominal pain, allergic reactions,
3 times daily; CHILD 6–8 years (20–30
anaphylactic shock, anaphylactoid
kg), 2 mg twice daily; CHILD 2–5 years
reactions, angioedema, drowsiness,
(13–20 kg), 1 mg 3 times daily.
dyspepsia, fatigue, flatulence,
Chronic diarrhea, by mouth, ADULT, initially 4
hypersensitivity, paralytic ileus,
mg, followed by 2 mg after each loose
megacolon, pruritus rash, toxic
stool (maximum, 16 mg daily),
megacolon, urinary retention, urticarial,
maintenance dose must be slowly titrated
vomiting, xerostomia.
downward to the minimum required to
Rare: Bullous eruption, erythema multiforme,
control symptoms (typically 4–8 mg daily,
Stevens-Johnson Syndrome, toxic
in divided doses), if no improvement is
epidermal necrolysis.
seen
after treatment with 16 mg for at least 10
Drug Interactions:
days, further use is unlikely to be of
Monitor closely with:
benefit.

Page | 24
ALIMENTARY TRACT AND METABOLISM
Ramosetron (constipation effects) - Enhances
therapeutic effects of Loperamide:
Administration: May be taken with or without
food.
Pregnancy Category: C
ATC Code: A07DA03
DRUGS USED IN DIABETES
INSULINS
GENERAL INFORMATION
Insulin is a polypeptide hormone of the
complex structure produced by the
pancreas that plays a key role in the
metabolism of carbohydrates, fats, and
proteins. All insulins are developed by
recombinant DNA technology but the
amino acid sequence of human and
insulin analogues differ. These explain
the differences in pharmacokinetics
between human and insulin analogues.
Mode of Action: Increase or restore the ability
to metabolize glucose by enhancing
cellular glucose uptake; inhibit
endogenous glucose output and
lipolysis.
Types of Insulin: The various formulations of
insulin are classified according to their
duration of action after subcutaneous
injection, as short and rapid-acting
insulins; intermediate-acting insulins;
and long-acting insulins.
The intermediate- and long-acting
insulins are given for the basal
requirements, while the short and
rapid-acting are given before meals to
control post-prandial hyperglycemia.
Indications:
Type 1 diabetes mellitus
Type 2 diabetes mellitus is inadequately
controlled with diet, exercise, and oral
antidiabetic medications, and where
oral therapy cannot be used (e.g.,
during surgery, or in pregnant women
with type 2 DM when diet alone fails to
control diabetes).
See under Interim Practice Guidelines
for Diabetes Mellitus.
Children with diabetes (especially those
presumed to have Type 1 diabetes
mellitus).
Diabetic emergencies, including diabetic
ketoacidosis and hyperosmolar
hyperglycemic states where IV short-
acting insulins are frequently used.
Contraindications: Known hypersensitivity to
insulin, or any of its excipients;
episodes of hypoglycemia.
Dose:
Dosage of insulin and regimen depends on the
individual treatment endpoints, and are
adjusted according to (capillary) blood
glucose monitoring.
Dosage of human insulin is always expressed
in units. The word “unit” should not be
abbreviated. One unit of human insulin
which is contained in 0.03846 mg of
the first International Standard (1986)
is equivalent to the amount of insulin
required to reduce the concentration of
blood glucose to 45 mg/dL in a fasting
rabbit
Dose Adjustments:
Renal Impairment: Insulin requirements may
increase in the presence of renal
impairment and therefore dose
reduction may be necessary. The
compensatory response to
hypoglycemia is impaired in renal
impairment.
For mild to moderate impairment, reduce the
dose. In severe impairment, insulin
requirements fall; refer to the internist
or diabetes specialist.
Page | 25
ALIMENTARY TRACT AND METABOLISM
Hepatic Impairment: Insulin requirements may
be decreased in patients with hepatic
impairment.
Precautions:
Dosage requirements are altered by many
factors. Acute illness or conditions, e.g.,
trauma, MI, infections, stroke, coma
(can worsen diabetes control; insulin-
treated diabetics may have increased
insulin requirements); infections are
more likely to develop in patients with
poorly controlled diabetes mellitus.
Driving (hazardous when hypoglycemic since
awareness is impaired; check blood
glucose concentration before driving
and, on long journeys, at intervals of
approximately two hours).
Diabetic ketoacidosis (occurs when
adjustments to insulin dosage fail to
compensate for increases in the
requirements of insulin, e.g., during
severe infection or a major intercurrent
illness)
Surgery.
Renal impairment (if severe; insulin
requirements fall; compensatory
response to hypoglycemia is impaired).
Pregnancy (strict blood glucose control,
especially at the time of conception and
early pregnancy to reduce risk of
spontaneous abortion and congenital
malformations; assess insulin
requirements frequently).
Exercise (may lower the body’s need for insulin
during and for some time after the
activity; it may also speed up the effect
of an insulin dose especially if the
exercise involves the area of injection
site); hot baths, sauna (may also
accelerate absorption after SC injection
by increasing skin blood flow).
MONITORING: The facility should have
monitoring at the point of care.
Blood glucose concentration varies
throughout the day; diabetics should
aim to maintain their pre-prandial
capillary blood glucose at 5 - 7.2
Page | 26
mmol/L (or 90-130 mg/dL), or FBS at 5
- 6.1 mmol/L (or 90-110 mg/dL).
Blood sugar should be prevented from falling
below 4 mmol/L because of the risk of
hypoglycemia.
Peak post-prandial capillary blood glucose
should be less than 10 mmol/L (or less
than 180 mg/dL).
Glycosylated hemoglobin concentration
(HbA1c) should be <7%.
STABILITY and STORAGE: Insulin preparations
should be stored in a refrigerator at 2-
8°C, protected from light, and not
allowed to freeze. It has been
recognized that patients may not follow
stringent storage guidelines, and most
manufacturers consider that storage at
a temperature of up to 25°C would be
acceptable for up to 1 month. Patients
should still be advised not to expose
their vials or cartridges to excessive
heat or sunlight
Adverse Drug Reactions:
Common: Hypoglycemia (see under Interim
Practice Guidelines in Diabetes
Mellitus).
Less Common: Edema, lipodystrophy (either as
lipoatrophy appearing as a depression
in the skin or as lipohypertrophy which
is an enlargement or thickening of
tissue) at the site of injection, weight
gain.
Rare: Localized reactions (or local allergy which
can consist of redness, swelling, and
itching), generalized hypersensitivity
reactions (including rash over the whole
body, shortness of breath, wheezing,
hypotension, tachycardia, or sweating,
or very rarely, anaphylactic reactions).
Drug Interactions:
Monitor closely with:
ACE inhibitors (e.g., enalapril) –may enhance
the hypoglycemic effect.
Alcohol – this decreases blood glucose
concentration by inhibiting the hepatic
glucose output and increasing the risk
ALIMENTARY TRACT AND METABOLISM
of hypoglycemia; can also mask
warning symptoms. BIPHASIC ISOPHANE
Beta-blockers (e.g., atenolol and propranolol) – Rx HUMAN INSULIN 70/30
these may enhance hypoglycemic
effect; may mask warning signs of
(RECOMBINANT DNA)
hypoglycemia, such as tremor.
Drugs increasing blood glucose concentration Inj.: 70% isophane suspension + 30% soluble
(e.g., glucocorticoids, antipsychotics, insulin in:
calcineurin in- 94 inhibitors, and high- 100 IU/mL, 5 mL and 10 mL vial (SC)
dose thiazide diuretics) –may increase 100 IU/mL, 3 mL disposable syringe
blood glucose concentration, and may (SC)
alter the control of diabetes by insulin. 100 IU/mL, 3 mL glass cartridge (SC)
Nifedipine – occasionally impaired glucose
tolerance.
A fixed ratio premix recombinant human insulin
Thiazolidinediones (TZDs) – in combination
formulation containing short-acting
with insulin are associated with an
insulin and intermediate-acting insulin
increased risk of edema and heart
(70% isophane insulin and 30% soluble
failure, especially in patients with
insulin). Human insulin is produced by
underlying cardiac disease.
recombinant DNA technology utilizing a
non-pathogenic laboratory strain of
Avoid concomitant use with:
Escherichia coli. It is a suspension of
Contraceptives, Oral (e.g., levonorgestrel and
crystals produced from combining human
medroxyprogesterone) – these
insulin and protamine sulfate under
antagonize the hypoglycemic effect of
appropriate conditions for crystal
insulin.
formation and mixing with human insulin
Corticosteroids (e.g., dexamethasone,
injection.
hydrocortisone, prednisolone) –
antagonism of hypoglycemic effect.
Indications: Management of diabetes mellitus.
Diuretics (e.g., furosemide and
hydrochlorothiazide) – antagonism of
Contraindications: See general information on
hypoglycemic effect.
Insulins noted above.
Administration: Insulin is given by injection
Dose:
because it is inactivated by the
by SC injection only.
gastrointestinal enzymes.
The subcutaneous (SC) route is ideal in most
NOTE: See the Section on Insulin Therapy
situations. It is usually injected in the
under Interim Practice Guidelines for
upper arms, thighs, buttocks, or
Diabetes Mellitus, Also see General
abdomen. The rate of absorption from
information on Insulins noted above for
different sites may vary depending on
further therapeutic information.
local blood flow (absorption in the arm
is faster than in the buttock or thigh).
WARNING:
Do NOT administer mixtures of insulin
NEVER administer biphasic isophane
formulations intravenously.
insulin intramuscularly or intravenously.
NOT suitable for the emergency treatment
of diabetic ketoacidosis.

Precautions:
Page | 27
ALIMENTARY TRACT AND METABOLISM
See General Information on Insulins noted
above.
Adverse Drug Reactions:
See General Information on Insulins noted
above.
Drug Interactions:
See General Information on Insulins noted
above.
Administration: For SC injection only. See
General Information on Insulins noted
above.
Shake the suspension gently before a
dose is withdrawn. Follow manufacturer’s
instructions.
Inspect visually before use. It should not
contain particulate matter and should
appear uniformly cloudy after mixing. Do
NOT use if particulate matter is seen. Do
NOT mix with other insulins or diluents.
Pregnancy Category: B
ATC Code: A1OAB3O; A1OAC3O
ISOPHANE HUMAN INSULIN
Rx / NPH HUMAN INSULIN
(RECOMBINANT DNA)
Inj.: 100 IU/mL, 3 mL pre‐filled syringe (SC)
100 IU/mL, 5 mL and 10 mL vial (SC)
Neutral Protamine Hagedorn (NPH Insulin) or
isophane insulin is a crystalline
suspension of human insulin with
protamine and zinc providing an
intermediate-acting insulin with slower
onset of action (within about 2 hours),
with peak activity at about 10-12 hours
and a longer duration of activity (up to
about 24 hours) than that of regular
insulin. It is of particular value for the
initiation of twice-daily insulin regimens.
Page | 28
NPH insulin is often combined with
regular insulin to achieve a more rapid
onset of action compared to NPH insulin
alone.
Indications: Management of diabetes mellitus.
Contraindications: See General Information on
Insulins noted above.
Dose:
For SC injection only.
NOTE: See the Section on Insulin Therapy
under Interim Guidelines for Diabetes
Mellitus for dosing. Also, see the General
information on Insulins noted above for
further therapeutic information.
WARNING:
NEVER administer isophane human insulin
intravenously.
NOT suitable for the emergency treatment
of diabetic ketoacidosis.
Precautions:
See General Information on Insulins noted
above.
Adverse Drug Reactions:
See General Information on Insulins noted
above.
Drug Interactions:
See General Information on Insulins noted
above.
Administration: For SC injection only. See
General Information on Insulins noted
above.
Shake the suspension gently before a
dose is withdrawn. Follow
manufacturer’s instructions.
Inspect visually before use. It should
not contain particulate matter and
should appear uniformly cloudy after
mixing. Do NOT use if particulate matter
is seen. Do NOT mix with other insulins
or diluents.
ALIMENTARY TRACT AND METABOLISM
Pregnancy Category: B
ATC Code: A1OACO1
REGULAR INSULIN
Rx (RECOMBINANT DNA,
HUMAN)
Inj.: 100 IU/mL, 3 mL pre‐filled syringe (SC,
IV/IM)
100 IU/mL, 5 ml and 10 mL vial (SC,
IV/IM)
A short-acting, sterile, clear aqueous solution
of regular crystalline zinc insulin, which
contains a polypeptide hormone
structurally identical to the human insulin
synthesized through rDNA technology for
the treatment of diabetes.
Regular or soluble insulin is the most
appropriate form of insulin for use in
diabetic emergencies and during surgery,
and in these cases is typically given in an
intravenous infusion (insulin drip). When
injected SC, it has a rapid onset of action
(30-60 minutes), a peak action between 2
and 4 hours, and a duration of action of
up to 8 hours. When injected IV, it has a
very short half-life of only about 5 minutes
and its effect disappears within 30
minutes.
Indications: Diabetes mellitus; diabetic
ketoacidosis
Contraindications: See General Information on
Insulins noted above.
Dose:
For SC, IM, or IV injection or IV infusion.
NOTE: Intravenous route of human regular
insulin is reserved for urgent treatment,
e.g., DKA, and fine control in serious
illness and peri-operatively.
NOTE: See the Section on Insulin Therapy
under Interim Practice Guidelines for
Diabetes Mellitus for dosing. Also, see the
General information on Insulins noted
above for further therapeutic information.
Administration:
Inspect visually before use. Shake the
suspension gently before withdrawing a
dose. Do NOT use if the solution is
viscous or cloudy. Follow
manufacturer’s instructions.
Pregnancy Category: B
ATC Code: A10AB30; A10AC30
BLOOD GLUCOSE LOWERING DRUGS,
EXCLUDING INSULINS
Biguanides
METFORMIN
Rx
Oral: 500 mg tablet/film coated tablet
850 mg tablet
A biguanide that exerts its effects by inhibiting
hepatic gluconeogenesis and increasing
peripheral glucose utilization, and is
useful in overweight and obese patients
since it does not increase weight nor
provoke hypoglycemia when used.
Indications: Type 2 Diabetes mellitus.
Contraindications: Ketoacidosis; severe
infection or trauma; dehydration; alcohol
misuse; moderate to severe heart failure;
risk of tissue hypoxia caused by sepsis,
respiratory failure, recent MI, or hepatic
impairment (withdraw treatment if tissue
hypoxia is likely to occur); use of iodine-
Page | 29
ALIMENTARY TRACT AND METABOLISM
containing X-ray contrast media (do not
restart metformin until renal function
returns to normal); use of general
anesthesia (suspend metformin on the
morning of surgery and restart when the
renal function returns to normal).
Dose:
Diabetes mellitus, by mouth, ADULT and CHILD
>10 years, initially 500 mg with breakfast
for at least 1 week, then 500 mg with
breakfast and evening meal for at least 1
week, then 500 mg with breakfast, lunch,
and evening meal, or 850 mg every 12
hours with or after food (usual maximum,
2.5 g daily in divided doses).
Dose Adjustments:
Elderly:
Use cautiously; monitor renal function and for
adverse effects; reduce dose (or stop
treatment), if necessary.
Renal and Hepatic Impairment: For mild-to-
moderate impairment, dose reduction is
warranted; for severe impairment, the
patient should be referred to a specialist.
Precautions:
WARNING: May cause lactic acidosis rarely
but with potentially severe consequences.
Severe renal and hepatic impairment
(increased risk of lactic acidosis); monitor
renal function before treatment and once
or twice annually (more frequently in the
elderly, or if deterioration is suspected).
Moderate-to-severe heart failure (may increase
risk of lactic acidosis).
Surgery (stop metformin before surgery;
monitor plasma glucose concentration;
restart when the patient is no longer
fasting and renal function has recovered);
substitute insulin during severe infection,
trauma or surgery.
Discontinue temporarily before intravascular
use of radiocontrast.
Pregnancy (all trimesters: avoid use – but may
be given for pregnant women previously
diagnosed with PCOS as prescribed by the
Page | 30
physician); breastfeeding (present in milk,
but safe in usual doses; monitor infant).
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, asthenia,
diarrhea, disturbance in taste,
dyspepsia, headache, indigestion,
flatulence, metallic taste, nausea,
upper respiratory tract infection,
vitamin B12 malabsorption, vomiting.
Less common: Erythema, pruritus, rash,
urticaria.
Rare: Acute hepatitis, lactic acidosis.
Drug Interactions:
Monitor closely with:
Alcohol – this decreases blood glucose
concentration by inhibiting the hepatic
glucose output, and increasing the risk
of hypoglycemia; can also mask
warning symptoms; increases the risk
of lactic acidosis.
Beta-blockers – these may mask some
hypoglycemic warning symptoms and
increase the incidence and severity of
hypoglycemia.
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, antipsychotics,
calcineurin inhibitors, and high-dose
thiazide diuretics) –may increase blood
glucose, and may alter the control of
diabetes by metformin.
Enalapril – possibly enhanced hypoglycemic
effect
Avoid concomitant use with:
Contraceptives, Oral – these antagonize the
hypoglycemic effect of metformin.
Furosemide – this antagonizes the
hypoglycemic effect of metformin.
Hydrocortisone – this antagonizes the
hypoglycemic effect of metformin
Administration: Take it with meals to reduce
stomach upset.
Pregnancy Category: B
ATC Code: A1OBA02
ALIMENTARY TRACT AND METABOLISM
Sulfonylureas
GLICLAZIDE
Rx
Oral: 30 mg tablet MR (modified-release)
80 mg tablet (immediate-release)
A second-generation sulfonylurea, which acts
by increasing the pancreatic insulin
secretion, and is useful in the treatment
of type 2 diabetes mellitus.
Indications: For the management of type 2
diabetes mellitus.
Contraindications: Known hypersensitivity to
gliclazide, and other sulfonamides or
sulfonylureas, or any component of the
formulation; type 1 diabetes mellitus
(insulin-dependent, IDDM); diabetic
ketoacidosis; diabetic precoma and
coma; severe renal or hepatic
impairment; stress conditions (e.g.,
serious infection, trauma, surgery);
porphyria; pregnancy; breastfeeding.
Dose:
NOTE: There is no fixed-dosage regimen for the
management of diabetes mellitus with
gliclazide. The dose should be
individualized based on frequent
monitoring of blood glucose during
dose titration and throughout
maintenance.
Type 2 diabetes, by mouth, ADULT,
As modified-release tablet: initially 30
mg once daily; titrate in 30 mg
increments every 2 weeks based on
blood glucose levels (maximum, 120
mg once daily);
As immediate-release tablet: initially 80
mg twice daily; titrate based on blood
glucose levels. Usual dosage range: 80-
320 mg/day (maximum, 320 mg/day);
dosage of ≥160 mg should be divided
into 2 equal parts for twice-daily
administration.
Dose Adjustments:
Renal Impairment: In severe renal impairment,
gliclazide is avoided (because of the
increased risk of hypoglycemia).
Hepatic Impairment: Avoid in severe hepatic
disease (since jaundice may occur).
Precautions:
Hypoglycemia (intermediate risk); stress-
related states (it may be necessary to
discontinue therapy and administer
insulin if the patient is exposed to
stressful conditions); cardiovascular
mortality; acute illness, including MI,
coma, trauma, infection (monitor blood
glucose and urine ketones; substitute
insulin treatment if glycemic control is
inadequate);
G6PD deficiency; sulfonamide allergy (use in
patients with sulfonamide allergy is
contraindicated in the product labeling
due to the risk of cross-reaction that exists
in patients with allergy to any of these
compounds, especially when the previous
reaction has been severe); surgery
(substitute insulin treatment before
surgery).
NOTE: Secondary failure: Loss of efficacy may
be observed following prolonged use as a
result of the progression of type 2
diabetes mellitus which results in
continued beta cell destruction. In
patients who were previously responding
to sulfonylurea therapy, consider
additional factors that may be
contributing to decreased efficacy (e.g.,
inappropriate dose, nonadherence to diet
and exercise regimen). If no contributing
factors can be identified, consider
discontinuing the use of the sulfonylurea
due to secondary failure of treatment.
Additional antidiabetic therapy (e.g.,
insulin) will be required.
Page | 31
ALIMENTARY TRACT AND METABOLISM
Adverse Drug Reactions:
Common: Dizziness, hypoglycemia, weight gain
Less common: Abdominal pain, angina
pectoris, arthralgia, arthrosis, back pain,
bronchitis, constipation, cough, diarrhea,
dyspepsia, headache, hypertension,
metallic taste, nausea, rash, rhinitis,
upper respiratory infection, urinary tract
infection, viral infection, vomiting.
Rare: Allergic reactions, blood disorders,
elevations of serum bilirubin, creatinine,
blood urea nitrogen, and hepatic
enzymes; erythema multiforme,
exfoliative dermatitis, fever, hepatic
failure, hepatitis, jaundice, malaise,
photosensitivity, Stevens-Johnson
syndrome.
the therapeutic effect of antidiabetic
agents.
Avoid concomitant use with:
CYP2C9 inhibitors (see Appendix) –
sulfonylureas are metabolized by
CYP2C9; when given with inhibitors of this
enzyme, their concentration may
increase, increasing the risk of
hypoglycemia.
St. John’s wort – this may decrease the
concentration of gliclazide, thus
decreasing its hypoglycemic effect.
Administration: Take a tablet (MR) with food to
minimize the risk of hypoglycemia.
Immediate-release tablets are best given
before meals.

Drug Interactions: Pregnancy Category: C

Monitor closely with:
Alcohol – this decreases blood glucose
concentration by inhibiting the hepatic VITAMINS
glucose output and increasing the risk of
hypoglycemia; can also mask warning
symptoms; gliclazide may enhance the MULTIVITAMINS, PLAIN
adverse effect of alcohol (a flushing
reaction may occur).
Beta-blockers – these may mask some
OTC MULTIVITAMINS
hypoglycemic warning symptoms and
increase the incidence and severity of
hypoglycemia.
Oral:
Corticosteroids, systemic – these may diminish
Composition:
the hypoglycemic effect of antidiabetic
Infants (per Children (per
agents. Loop
1 mL drops) 5 mL syrup
Diuretics – these diminish the hypoglycemic
Vitamin A 325 – 380 350 – 400
effect of hypoglycemic agents.
mcg mcg
Ranitidine – this may increase the serum
concentration of sulfonylureas. Vitamin 0.2 – 0.4 0.5 – 1.0 mg
Rifampicin – this may increase the metabolism B1 mg
of gliclazide, decreasing its hypoglycemic Vitamin 0.3 – 0.4 0.7 – 0.9 mg
effect. Salicylates – these may enhance B2 mg
the hypoglycemic effect of hypoglycemic Vitamin 0.3 – 0.6 0.9 – 1.6 mg
agents. B6 mg
Sulfonamide Derivatives – these may enhance Vitamin 0.3 – 0.4 0.9 – 3.0
the hypoglycemic effect of sulfonylureas. B12 mcg mcg
Thiazide Diuretics – these may diminish Vitamin C 30 mg 35 – 55 mg

Page | 32
ALIMENTARY TRACT AND METABOLISM
Vitamin D 200 IU – 200 IU –
400 IU (5 - 400 IU (5 - Administration: May be taken with or without
10 mcg) 10 mcg) food. It may be taken with meals for better
Vitamin E 3 – 4 mg 5 – 7 mg absorption or if GI discomfort occurs.
Folic Acid 20 – 65 40 – 300
mcg mcg Pregnancy Category: Not available
Niacin 1 – 5 mg 5 – 18 mg
ATC Code: A11BA
Adult (per
tablet/capsule)
Vitamin A 600 – 700 mcg or VITAMIN A AND D
2,000 – 2,500 IU
Vitamin B1 1.3 – 1.7 mg
Vitamin B2 0.7 – 1.3 mg
RETINOL (VITAMIN A)
Vitamin B6 1.6 – 2 mg Rx
Vitamin B12 2 – 6 mcg
Vitamin C 60 - 80 mg
Vitamin D 400 IU (10 mcg) Oral: 10,000 IU, 25,000 IU and 50,000 IU
Vitamin E 6 – 10 mg (15 – 30 IU) softgel capsule
Folic Acid 400 mcg 100,000 IU and 200,000 IU soft gel
Niacin 13 – 23 mg capsule with nipple (only for DOH
A dietary supplement containing essential program) (B)
multivitamins and minerals that are
needed for good health, growth, and A fat-soluble vitamin and dietary supplement
development. that is required by the eyes for the
transduction of light into neural signs
Indications: Dietary supplementation, necessary for vision.
management of vitamin deficiencies
Indications: For the prevention and treatment
Contraindications: Known hypersensitivity to of vitamin A deficiency states (e.g.,
any component of the preparations xerophthalmia and night blindness);
prevention of complications of measles.
Dose:
Prevention or treatment of vitamin Contraindications: Hypervitaminosis A; known
deficiencies, by mouth, ADULT, 1 tablet hypersensitivity to vitamin A, or any
or capsule daily. component of the formulation; dosages
exceeding the Recommended Energy and
Precautions: Nutrient Intake (RENI); women who are, or
Avoid taking similar vitamin products may become, pregnant.
NOTE: Not all products can be used in children
of all age groups. Consult specific product Dose:
labeling before use. Do NOT exceed Prevention of vitamin A deficiency (universal or
recommended doses. targeted distribution programs), by
mouth, ADULT, 200,000 IU every 6
Drug Interactions: months; ADULT (pregnant woman),
Decreases serum concentration of certain maximum of 10,000 IU daily or
components of Multivitamins: Food, e.g., maximum 25,000 IU weekly; ADULT
eggs, milk (inhibits the absorption of iron) (woman of childbearing age), 200,000

Page | 33
ALIMENTARY TRACT AND METABOLISM
IU at delivery or within 8 weeks of
delivery; CHILD >1 year (preschool),
200,000 IU every 4–6 months; INFANT
6–12 months, 100,000 IU every 4–6
months, preferably at measles
vaccination; INFANT <6 months 50,000
IU [Note: Administer an additional dose
the next day in hospitalized children
with measles infection]
Treatment of xerophthalmia, by mouth, ADULT
(except woman of childbearing age)
and CHILD >1 year, 200,000 IU on
diagnosis, repeated the next day and
again after 2 weeks; ADULT (woman of
childbearing age with severe signs of
xerophthalmia), as for other adults;
ADULT (woman of childbearing age with
less severe symptoms, e.g., night
blindness), either 5,000 to 10,000 IU
daily for at least 4 weeks or up to
25,000 IU weekly; INFANT 6– 12
months, 100,000 IU immediately on
diagnosis, repeated the next day and
again after 2 weeks; INFANT under 6
months, 50,000 IU on diagnosis, repeat
the next day and again after 2 weeks.
[NOTE: Oral vitamin A preparations are
preferred for the prevention and
treatment of vitamin A deficiency.]
Dose Adjustments:
Pregnant women susceptible to vitamin A
deficiency during the third trimester:
Should be given low dose vitamin A
supplements on a daily or weekly basis.
Precautions:
WARNING: Severe congenital malformations
may occur in infants of mothers consuming
large amounts of oral retinoids for acne
treatment.
Patients on prolonged daily administration
over 25,000 IU should be under close
supervision;
Chronic intake of vitamin A at levels 10–20
times the RDA can lead to
hypervitaminosis A;
Page | 34
Pregnancy (excessive doses during the first
trimester may be teratogenic);
Breastfeeding (there is theoretical risk of
toxicity in infants of mothers taking large
doses).
NOTE: Dietary reference intakes (DRIs):
Tolerable upper intake level (UL) for adults
is 3,000 micrograms daily of preformed
vitamin A, based on teratogenicity as the
critical adverse effect for women of
childbearing age and liver pathology for all
other adults.
Adverse Drug Reactions:
Less common: Diplopia, headache, nausea,
symmetric papilledema, vomiting
Rare: Birth defects (e.g., tense and bulging
fontanelle in infants), dry hair, enlarged
liver, increased intracranial pressure
Drug Interactions:
Monitor closely with:
Warfarin – Retinol increases its therapeutic
effect (anticoagulant effect)
Avoid concomitant use with:
Drugs that decrease absorption of Retinol:
Bile Acid–binding Resins, e.g.,
Cholestyramine, Colestipol
Retinoid Drugs, e.g., All-trans-retinoic Acid,
Isotretinoin (hypervitaminosis A);
Tetracyclines (benign intracranial
hypertension) since Retinol (Vitamin A)
can increase the risk of adverse or toxic
effects of these drugs
Administration: This vitamin is absorbed along
with fat in the diet. Take it with food.
Pregnancy Category: A; X if dose is greater than
RENI
ATC Code: A11CA01
ALIMENTARY TRACT AND METABOLISM
ASCORBIC ACID (VITAMIN C) Scurvy, by mouth, ADULT, 100–250 mg 1–2
times daily; CHILD, 100–300 mg daily
in divided doses; INFANT, 50– 100 mg
ASCORBIC ACID daily in divided doses
OTC
(VITAMIN C) Adjunct to deferoxamine therapy in the
treatment of chronic, iron toxicity, by
mouth, ADULT, 100–200 mg once daily
Oral: 100 mg and 500 mg tablet
initiated 1–2 hours after deferoxamine
100 mg/5 mL syrup, 60 mL and 120
infusion is started.
mL
Chronic recurrent furunculosis in patients with
100 mg/mL drops, 15 mL and 30 mL
neutrophil dysfunction, by mouth,
ADULT, 1,000 mg daily for 4–6 weeks
A water-soluble vitamin that acts as a free [NOTE: Studies show that ascorbic acid
radical, an antioxidant scavenger, and does not alter the course of
plays a major role in oxidation-reduction furunculosis in patients without
reactions. Ascorbic acid is a cofactor for neutrophil dysfunction].
enzymes involved in the biosynthesis of
collagen, carnitine, and Dose Adjustments:
neurotransmitters. Renal Impairment: Removed by hemodialysis.
Adjust dosing accordingly. For patients
Indications: Nutritional supplementation; receiving intermittent hemodialysis,
management of iron toxicity, scurvy doses greater than 200 mg daily are not
recommended.
Contraindications: Anemia, breastfeeding, Precautions:
diabetes mellitus, G6PD deficiency, Heart failure (do not administer concurrently
hemochromatosis, nephrolithiasis, with deferoxamine without the approval of
pregnancy, sideroblastic anemia, their health care professional);
sodium restriction, sulfite Hyperoxaluria;
hypersensitivity, tartrazine dye Renal impairment;
hypersensitivity, thalassemia Lactation

Dose:
Adverse Drug Reactions:
Nutritional supplementation, by mouth, ADULT
Common: Renal tubular obstruction (oxalate,
(male), 90 mg once daily, or 100 mg
urate, or cystine renal stones), lower
once or twice daily; ADULT (female), 75
back pain (costovertebral),
mg once daily, or 100 mg once or twice
hyperoxaluria, flushing, headache,
daily; ADULT and ADOLESCENT
nausea, vomiting, abdominal cramps,
(pregnant female), 80-85 mg once
diarrhea, flatulence, heartburn, dental
daily; ADULT and ADOLESCENT
caries (chewable tablets), fatigue,
(lactating female), 115–120 mg once
insomnia, sleepiness
daily; ADULT (male smokers), 125 mg
Less common: Hemolytic anemia
once daily; ADULT (female smokers),
Rare: Sickle-cell crisis
110 mg once daily; ADOLESCENT
(male), 75 mg once daily; ADOLESCENT
Drug Interactions:
(female), 65 mg once daily; CHILD 9–
NOTE: Decreases urine pH, which may cause
13 years, 45 mg once daily; CHILD 4–8
an increase in the excretion of alkaline
years, 25 mg once daily; CHILD 1–3
drugs and an increase in renal tubular
years, 15 mg once daily; INFANT, 40–
reabsorption of acidic compounds.
50 mg once daily

Page | 35
ALIMENTARY TRACT AND METABOLISM
Monitor closely with:
Mexiletine, Propranolol [take ascorbic acid at
least 1 hour before propranolol]
(bradycardic effect): Ascorbic acid
decreases the therapeutic effect of
these drugs
Iron Salts, Polysaccharide-Iron Complex:
Ascorbic acid increases absorption of
these drugs:
Avoid concomitant use with:
Disulfiram; Warfarin (anticoagulation effects) -
Ascorbic acid decreases the therapeutic
effect of these drugs
Deferoxamine - Ascorbic acid increases the risk
of adverse or toxic effects of this drug
(e.g., impairment of cardiac function,
causing cardiac decompensation):
Administration: May be taken without regard to
meals. Administer with a full glass of
water.
Pregnancy Category: C
OTHER PLAIN VITAMIN PREPARATIONS
OTC FOLIC ACID
Oral: 400 mcg, 800 mcg, 1 mg, and 5
mg tablet /capsule
2.5 mg/mL pediatric drops
5 mg/mL syrup
Also known as Vitamin B9, it is reduced in the
body to tetrahydrofolate, which is a
coenzyme for various metabolic
processes, including the synthesis of
purine and pyrimidine nucleotides, and
hence in the synthesis of DNA. It is also
involved in some amino acid conversions
and the formation and utilization of
formate. Folic acid is also used in women
Page | 36
of childbearing potential and pregnant
women to protect against neural tube
defects in their offspring.
Indications: Treatment of megaloblastic and
macrocytic anemias due to folate
deficiency; used for diarrhea in pediatric
patients.
Contraindications: Hypersensitivity to folic acid
or any component of the formulation.
Dose:
Anemia, by mouth, ADULT, 0.4 mg daily;
PREGNANT and LACTATING WOMEN, 0.8
mg daily; CHILD <4 years up to 0.3 mg
daily; INFANT 0.1 mg daily
Adequate intake (expressed as folate
equivalents), by mouth, INFANT 7–12
months, 80 micrograms daily; INFANT 1–
6 months, 65 micrograms daily.
Recommended daily allowance, RDA
(expressed as dietary folate equivalents),
by mouth, ADULT, 400 micrograms daily;
PREGNANT WOMEN, 600 micrograms
daily; LACTATING WOMEN, 500
micrograms daily; CHILD 9–13 years, 300
micrograms daily; CHILD 4–8 years, 200
micrograms daily; CHILD 1–3 years, 150
micrograms daily.
Dose Adjustments:
Geriatric: Vitamin B12 deficiency must be ruled
out before initiating folate therapy due to
the frequency of combined nutritional
deficiencies. RDA requirements, 400
micrograms daily (minimum, 0.4 mg).
Precautions:
Anemia (not appropriate for monotherapy with
pernicious, aplastic, or normocytic
anemias when anemia is present with
vitamin B12 deficiency); pernicious
anemia (doses >0.1 mg daily may obscure
pernicious anemia with continuing
irreversible nerve damage progression);
Depressed hematopoiesis, alcoholism, and
deficiencies of other vitamins.
Elderly;
ALIMENTARY TRACT AND METABOLISM
Neonates; hypoprothrombinemia caused by liver
Lactation (excreted in breastmilk; increased disease.
folate requirement).
Dose:
Adverse Drug Reactions: Prophylaxis of hemorrhagic disease of the
Flushing, malaise, erythema, pruritus, rash, newborn, by IM injection, NEONATE, 0.5-1
bronchospasm, allergic reaction mg as a single dose; by mouth, NEONATE,
2 mg followed by a second dose after 4-7
Drug Interactions: days and for breastfed babies a third dose
Avoid concomitant use with: after 1 month.
Raltitrexed - Folic acid reduces the therapeutic Treatment of hemorrhagic disease of the
effect of this drug newborn, by slow IV or IM injection,
NEONATE, 1 mg (with further doses if
Pregnancy Category: A necessary, at 8-hour intervals).

ATC Code: Not available Dose Adjustments:

Geriatric: Dose should be at the lower end of
the recommended range
Hepatic Impairment: For mild-to-moderate
PHYTOMENADIONE impairment, use with caution. For severe
Rx (PHYTONADIONE, VITAMIN impairment, refer the patient to a
specialist.
K1)
Precautions:
Hepatic impairment; Elderly.
Oral: 2mg/0.2 mL pediatric ampule (as mixed
NOTE: Fat-soluble Vitamin. Patients with fat
micelle)
malabsorption, especially in biliary
Inj.: 10 mg/mL, 1 mL ampul (IM, IV, SC) (as
obstruction or hepatic disease may
aqueous colloidal solution with benzyl
become Vitamin K deficient.
alcohol)
10 mg/mL, 1 mL ampul (IM, IV, SC) (as
mixed micelle) Adverse Drug Reactions:
Common: Erythema, flushing, nausea, pain,
tenderness, tiredness, vomiting,
A fat-soluble vitamin that is an essential
warmth sensation
cofactor in the synthesis of blood
Less common: Allergic reactions (including
coagulation factors: prothrombin (II),
anaphylaxis), bradycardia,
proconvertin (VII), plasma thromboplastin
bronchospasm, dizziness, dyspnea,
component (IX), Stuart factor (X), and
hypo- tension, rebound bleeding
proteins C and S.
Rare: Anaphylactoid reactions, hemolytic
anemia, hyperbilirubinemia,
Indications: Treatment and prophylaxis against
kernicterus
the hemorrhagic disease of the newborn.
Drug Interactions:
Contraindications: Known hypersensitivity to
Monitor closely with:
phytomenadione or any component of the
Drugs that decrease the therapeutic effect of
formulation; avoid IM if bleeding;
Phytomenadione:
pregnancy (3rd trimester); it is not
Anticonvulsants, e.g., Phenobarbital,
effective in hereditary
Phenytoin, Antituberculosis Drugs, e.g.,

Page | 37
ALIMENTARY TRACT AND METABOLISM
Isoniazid, Rifampicin (may cause vitamin
K deficiency bleeding on the first day of Dose:
life in newborns) Prevention and treatment of vitamin B complex
deficiency, by mouth, ADULT, 1–2 tablets
Avoid concomitant use with: or capsules daily
Anticoagulant, e.g., Warfarin which (increases
synthesis of blood clotting factors): Precautions:
Phytomenadione decreases the Vitamin B12 >10 micrograms daily may
therapeutic effect of these drugs. produce a hematological response in folic
acid deficiency.
Administration: IV administration should be Neurotoxicity (long-term administration of
slow, over 30 seconds. Rapid infusion can large doses >2 g daily)
cause dyspnea, chest pain, and back Malabsorption;
pain. Anemia;
Neuropathy;
Pregnancy Category: C; X in 3rd trimester or Undiagnosed vitamin B12 deficiency.
near term
Adverse Drug Reactions:
Less common: Headache, peripheral
VITAMIN B1, PLAIN AND IN neuropathy (high doses)
COMBINATION WITH VITAMIN B6 AND Rare: Hypersensitivity reactions
B12
Drug Interactions:
Avoid concomitant use with Levodopa (vitamin
B1 B6 B12 decreases its therapeutic
OTC VITAMIN B1 B6 B12 effect)

Administration: For oral administration, may be

Oral: 100 mg B1 + 5 mg B6 + 50 microgram taken with or without food. May be taken
B12 per tablet/capsule with meals to reduce GI discomfort.

A dietary supplement, which contains vitamins Pregnancy Category A; C (doses greater than
B1, B6, and B12 for nerve cell RENI)
metabolism, and for vitamin B-complex
deficiencies. ATC Code: A11DB

Indications: Prevention and treatment of

vitamin B complex deficiencies; adjunct in
the management of neuromuscular pain MINERAL SUPPLEMENTS
responsive to vitamin B1, B6, and B12,
including neuralgia, neuritis, and
CALCIUM
neuropathies.

Contraindications: Leber’s disease or tobacco GENERAL INFORMATION

amblyopia; known hypersensitivity to any An essential cation for the maintenance of the
component of the formulation. nervous, muscular, and skeletal systems,
as well as for cell membrane and capillary
permeability. It is the primary component

Page | 38
ALIMENTARY TRACT AND METABOLISM
of skeletal tissue, providing structural
integrity and support for individual growth.
Indications: Nutritional supplementation;
osteoporosis prophylaxis. cardiac arrest;
cardiopulmonary resuscitation; exchange
transfusion-induced hypocalcemia
prophylaxis; hyperkalemia;
hypermagnesemia; hyperphosphatemia;
hypocalcemia;
Contraindications: Breastfeeding; cardiac
arrhythmias; dehydration; digitalis toxicity;
extravasation; hypercalcemia;
hypercalciuria; necrotizing enterocolitis;
hyperphosphatemia; hypoparathyroidism;
pregnancy; sarcoidosis; ventricular
fibrillation; diarrhea; vitamin D toxicity.
Dose Adjustment:
Renal Impairment: In end-stage renal disease,
administer with meals (e.g., 10– 15
minutes before or during).
Adverse Drug Reactions:
Common: Mild to severe local irritation, chalky
taste, flushing, tingling sensation,
hypotension (dizziness, syncope), sinus
bradycardia, cardiac arrhythmias, cardiac
arrest, diarrhea, gastric irritation.
Less Common: Milk-alkali syndrome, muscle
cramps
Drug Interactions:
Monitor closely with:
Drugs that decrease absorption of Calcium:
Corticosteroids
Dibasic Sodium Phosphate, Anhydrous,
Monobasic Sodium Phosphate,
Monohydrate, Phenytoin (forms
nonabsorbable complexes), Phosphorus
Salts, Strontium-89 Chloride: Calcium
decreases absorption of these drugs
Magnesium Salts (neutralized by Calcium)
Calcium decreases the therapeutic effect
Calcitriol (hypercalcemia), Vitamin D Analogs
(Vitamin D-induced hypercalcemia):
Calcium increases the risk of adverse or
toxic effects of these drugs
Avoid concomitant use with:
Bisphosphonates e.g. Alendronate (administer
at least 2 hours apart) - Calcium
decreases its absorption
Fluoroquinolones e.g., Levofloxacin,
Quinolones [administer at least 2 hours
before or 6 hours after Calcium Salts],
Tetracyclines [administer at least 1 hour
before Calcium Salts], Thyroid Hormones
[administer at least 4 hours before or
after Calcium Salts] (forms
nonabsorbable complexes) - Calcium
decreases the bioavailability of these
drugs.
Vitamin A - Decreases the therapeutic effect of
Calcium
Calcitonin, Nondepolarizing Neuromuscular
Blockers, Sucralfate [stagger doses], Thyroid
Hormones (hypothyroidism) - Calcium
decreases the therapeutic effect of these
drugs
Vitamin A (bone loss) - Calcium Decreases the
therapeutic effect of these drugs
Cardiac Glycosides e.g., digoxin (arrhythmias),
Ceftriaxone (fatal reactions involving
ceftriaxone (calcium precipitates in the
lungs and kidneys), Sodium Bicarbonate,
Thiazide Diuretics (milk-alkali syndrome) -
Calcium increases the risk of adverse effects
of these drugs
Pregnancy Category: C
OTC CALCIUM CARBONATE
Oral: tablet/chewable tablet (equiv. to 500
mg and 600 mg elemental calcium)
An inorganic Calcium salt is useful in the
treatment of hyperphosphatemia
secondary to chronic renal failure.
Indications: Management of
hyperphosphatemia, hypocalcemia, and
premenstrual syndrome (PMS); nutritional
Page | 39
ALIMENTARY TRACT AND METABOLISM
supplementation; prevention of
osteoporosis.
Contraindications: Breastfeeding;
constipation; dehydration; GI bleeding; GI
obstruction; hypercalcemia;
hyperparathyroidism; ileus;
hypercalciuria; necrotizing enterocolitis;
neoplastic disease; nephrolithiasis; peptic
ulcer disease; pregnancy; renal disease;
sarcoidosis.
Dose:
Hypocalcemia, by mouth, ADULT, 5–10 g daily
(equivalent to 2–4 g elemental calcium),
given in 3–4 divided doses; CHILD,
112.5–162.5 mg/kg daily (equivalent to
45–65 mg/kg), given in 4 divided doses;
NEONATE, 125–375 mg/kg daily
(equivalent to 50–150 mg/kg), given in
4–6 divided doses (maximum dose, 1 g
daily).
Nutritional supplementation and prevention of
osteoporosis, by mouth, ADULT ≥51
years, 2,500–3,750 mg daily (equivalent
to 1,000 to 1,500 mg elemental calcium);
ADULT 19–50 years, 2,500 mg daily
(equivalent to 1,000 mg elemental
calcium); ADOLESCENT and CHILD 9–18
years, 3,250 mg daily (equivalent to
1,300 mg elemental calcium); CHILD 4–8
years, 2,000 mg daily (equivalent to 800
mg elemental calcium); CHILD 1–3 years,
1,250 mg daily (equivalent to 500 mg
elemental calcium); INFANT 6–12
months, equivalent to 270 mg elemental
calcium, based on total intake; INFANT <6
months and NEONATE equivalent to 210
mg elemental calcium, based on total
intake
Dose Adjustments:
Renal Impairment: In CrCl <30 mL/mi, use with
caution
Precautions:
Renal impairment;
Hypoparathyroid disease;
Hypercalcemia-associated diseases;
Page | 40
Achlorhydria;
History of kidney stones
Adverse Drug Reactions:
Common: Gastric hypersecretion, acid
rebound, flatulence, gastric distention,
constipation, eructation
Less common: Hypercalcemia, nephrolithiasis,
milk-alkali syndrome, renal failure
Rare: Hypophosphatemia
Drug Interactions:
Monitor closely with:
Corticosteroids, systemic - Decreases
absorption of Calcium:
Calcipotriene, Calcitriol (hypercalcemia),
Mefloquine, Thiazide Diuretics
(hypercalcemia), Vitamin D Analogues
(Vitamin D-induced hypercalcemia) -
Calcium increases the risk of adverse
effects of these drugs
Avoid concomitant use with:
Bisacodyl [administer at least 1 hour apart]
Bisphosphonates e.g., Alendronate
[administer at least 2 hours apart];
Cefuroxime, oral [administer at least 1
hour before or 2 hours after Calcium
Carbonate]; Itraconazole [administer at
least 2 hours after Itraconazole];
Ketoconazole, Oral [administer at least 2
hours after Ketoconazole]; Phenytoin, oral
[administer Calcium Carbonate at least 1
hour before or 6 hours after Phenytoin]
Rifampin [administer at least 1 hour
apart] – Calcium decreases absorption of
these drugs.
Fluoroquinolones e.g., Levofloxacin
[administer at least 2 hours before or 6
hours after Calcium Salts], Quinolones
[administer at least 2 hours before or 6
hours after Calcium Salts], Tetracyclines
[administer at least 1 hour before Calcium
Salts], Thyroid Hormones [administer at
least 4 hours before or after Calcium
Salts] (forms non-absorbable
complexes):- Calcium decreases the
bioavailability of these drugs:
ALIMENTARY TRACT AND METABOLISM
Ezetimibe and Rosuvastatin [administer at
least 1 hour before or 2 hours after
Calcium Carbonate] - Calcium Decreases
serum concentration of the following
drugs
Vitamin A - Decreases the therapeutic effect of
Calcium
Calcitonin, Cefuroxime (decrease antibiotic
efficacy), Sucralfate [stagger doses],
Thyroid Hormones (leads to
hypothyroidism) - Calcium decreases the
therapeutic effect of the following drugs:
Quinidine - Calcium decreases its urinary
excretion
Vitamin A (bone loss) - Increases risk of
adverse effects of Calcium
Sodium Bicarbonate (milk-alkali syndrome -
Increases risk of adverse effects
Not to be used concomitantly with Calcium
Carbonate: Ammonium Chloride
Administration Administer with meals to
improve absorption. Follow each dose
with appropriate fluid intake.
Separate administration with other medicines
to prevent interactions.
Pregnancy Category: C
ATC Code: A12AA04
CALCIUM GLUCONATE
Rx
Inj: 10%, 10 mL ampul/vial (IV)
10%, 20 mL and 25 mL bottle (IV)
An organic Calcium salt that is used to prevent
or treat negative calcium balance. It also
helps facilitate nerve and muscle
performance as well as normal cardiac
function.
Indications: Treatment of acute magnesium
toxicity seen in the obstetric setting in
patients receiving magnesium sulfate for
eclampsia (for primary health facilities
with BeMONC and the CEmONC units).
NOTE: In this situation, magnesium
toxicity can present as follows: depressed
deep tendon reflexes, cardiopulmonary
arrest, and respiratory depression. The
toxicity arises from the blockage of
calcium and potassium channels due to
magnesium. Calcium gluconate treats
hypermagnesemia by directly
antagonizing magnesium at the
neuromuscular junction.
Contraindications: Ventricular fibrillation;
metastatic bone disease; injection into
myocardium; renal calculi; hypercalcemia
and predisposition to hypercalcemia (e.g.,
hyperparathyroidism, certain
malignancies); above normal serum
calcium levels; concomitant
administration of ceftriaxone in neonates.
Dose:
NOTE: 1 g calcium gluconate = 90 mg (4.5
mEq, 9.3%) elemental calcium.
Hypermagnesemia, by IV administration,
ADULT, 1,000– 2,000 mg (10–20 mL)
single dose at a rate not exceeding
0.5–2 mL/minute in symptomatic
hypermagnesemia.
If with cardiac toxicity due to
hypermagnesemia, the following is
given: 10% solution, 15 to 30 mL slow
IV over 2 to 5 minutes during cardiac
arrest from hypermagnesemia.
Precautions:
Impaired renal function; cardiac disease;
hypercalcemia-associated diseases, e.g.,
sarcoidosis.
Lactation (excreted in breastmilk; use with
caution).
Administration: Administer by slow IV injection
as a 10% solution slowly through a small
Page | 41
ALIMENTARY TRACT AND METABOLISM
needle into a large vein to avoid a rapid A two-component dietary supplement of
increase in serum calcium and calcium and fat-soluble vitamin D, which
extravasation of calcium solution into the serves to increase the calcium pool
surrounding tissue that may lead to tissue available into the bones.
necrosis. Following IV injection, the
patient should remain recumbent for a Indications: Adjunct in osteoporosis;
short time therapeutic supplementation (e.g.,
lactose intolerance or with milk allergy);
Visually inspect parenteral products for established vitamin D dependent
particulate matter and discoloration osteomalacia; post-menopausal women;
before administration. chronic kidney disease with or without
renal replacement therapy;
Close monitoring of serum calcium hyperphosphatemia.
concentrations is essential during IV
administration of calcium. Contraindications:
Hypercalcemia, hyperparathyroidism;
Oral administration of calcium renal calculi; hypophosphatemia; vitamin
supplements or calcium-rich foods should D toxicity; abnormal sensitivity to the
replace IV calcium therapy as soon as effects of vitamin D; malabsorption
possible. syndrome; renal failure or severe renal
impairment; known hypersensitivity to the
NOTE: Do NOT administer by IM or SC preparation or any of the excipients (e.g.
route. soya oil).

Closely monitor serum calcium Dose:

concentrations during IV administration of Calcium deficiency, by mouth, ADULT,
calcium. supplementary intake to achieve a total
elemental calcium dosage of 1 g in 2
Oral administration of calcium divided doses for male and
supplements or calcium-rich foods should premenopausal female patients;
replace IV calcium therapy as soon as 1.2–1.5 g in 3 divided doses for
possible postmenopausal women.
NOTE: Not recommended for children
ATC Code: A12AA03
Dose Adjustments:
NOTE: Check Recommended Energy and
Nutrient Intakes (RENI) per day for
CALCIUM CARBONATE + Calcium and Vitamin D for dosing of
OTC different population groups
CHOLECALCIFEROL
(VITAMIN D3) Precautions:
Should not be used in osteoporosis due to
Oral: Equiv. to 500 mg elemental Ca + 400 prolonged immobilization, renal stones, or
IU Vit. D3 severe hypercalciuria;
Equiv. to 600 mg elemental Ca + 400 Mild to moderate renal failure or mild
IU Vit. D3 hypercalciuria (supervise carefully,
including periodic checks of plasma
calcium levels and urinary calcium
excretion);
Page | 42
ALIMENTARY TRACT AND METABOLISM
History of renal stones;
Patients receiving treatment for cardiovascular
diseases;
Rare hereditary problems of glucose-galactose
malabsorption or fructose intolerance;
Achlorhydria;
Hypercalcemia and hypercalciuria.
NOTE: Allowances should be made for calcium
and vitamin D supplements from other
sources.
Adverse Drug Reactions:
Less common: Hypercalcemia, hypercalciuria
Rare: Abdominal pain, acid rebound, anorexia,
arrhythmia, bone or muscle pain,
constipation or diarrhea, headache,
hypophosphatemia, flatulence, loss of
appetite, metallic taste, milk-alkali
syndrome, nausea, pruritus, rash,
urticaria, vomiting, xerostomia
Drug Interactions:
Monitor closely with:
Corticosteroids - Decreases absorption of
Calcium.
Quinolone Antibiotics, e.g., Ciprofloxacin -
absorption of these drugs can decrease
Digoxin (hypercalcemia), Thiazide Diuretics
(hypercalcemia; milk-alkali syndrome with
high doses) - risk of adverse effects of
these drugs can increase
Avoid concomitant use with:
Iron Salts, Levothyroxine, Tetracyclines, Zinc
Salts – Absorption of these drugs can
decrease
Bisphosphonate e.g., Alendronate - Serum
concentration of these drugs can
decrease
Calcium Channel Blockers e.g., Amlodipine -
Therapeutic effect can be decreased
FOOD INTERACTION. Foods that are rich in
oxalic acid (e.g., spinach) and phytic acid
(e.g., whole cereals) may reduce calcium
absorption due to the formation of
insoluble calcium salts.
Do NOT take calcium products within 2
hours of eating such foods.
Administration: Administer, preferably with
food, 2 hours before or after other
medications. Maintain adequate fluid
intake. The administration is followed by
increased serum gastric acid secretion,
within 2 hours.
Pregnancy Category: C
ATC Code: A12AX
OTHER MINERAL PRODUCTS
OTC FERROUS SALT
Oral: tablet, (equiv. to 60 mg elemental iron)
solution, (equiv. to 15 mg elemental
iron/0.6 mL)
drops, 15 mL and 30 mL
solution, (equiv. to 30 mg elemental
iron/5 mL)
syrup, 60 mL
Note: The elemental iron content of a
ferrous salt depends on the type of
preparation as follows:
Ferrous fumarate – 33%
Ferrous gluconate – 12%
Ferrous lactate – 19%
Ferrous sulfate, hydrated – 20%
Ferrous sulfate, desiccated – 32%
An essential trace element required for the
formation of hemoglobin and the efficient
oxygen transport in the blood.
Indications: Treatment of iron-deficiency
anemia and supplement and prophylaxis
in people on hemodialysis receiving
erythropoietin.
Page | 43
ALIMENTARY TRACT AND METABOLISM
Contraindications: Anemia not due to iron
deficiency; parenteral iron therapy; in
patients receiving repeated blood
transfusions; hemochromatosis;
hemosiderosis
Dose:
Iron-deficiency anemia, by mouth, ADULT,
elemental iron, 100–200 mg daily in
divided doses.
Prevention of iron-deficiency anemia (in those
at risk), by mouth, ADULT (woman),
elemental iron 60 mg daily; CHILD >5
years, elemental iron 30 mg daily;
CHILD < 5 years, elemental iron 2
mg/kg daily (maximum 30 mg).
NOTE: For women and children > 5 years old,
folic acid may also be given.
Precautions:
WARNING:
May exacerbate GI bleeding. Use with
caution in patients with GI disorders.
Not to be administered for longer than 6
months (monitor closely for potential
complications);
Transfusion-dependent anemia;
Peptic ulcer;
Regional enteritis;
Ulcerative colitis;
Intestinal strictures;
Diverticula;
Pregnancy (avoid use in the first trimester;
administer only in women with low-normal
hemoglobin).
NOTE: In cases of overdose, initiate therapy
with deferoxamine. Before administration
of deferoxamine, the stomach should be
emptied by gastric lavage (with a wide-
bore tube), preferable within one hour of
ingesting a significant quantity of iron or if
radiography reveals tablets in the
stomach.
Adverse Drug Reactions:
Page | 44
Common: Abdominal pain, black discoloration
of feces, constipation, diarrhea, nausea,
vomiting
Less common: Black discoloration of teeth
Rare: Anaphylaxis, GI erosion, and perforation,
hemosiderosis
Drug Interactions:
Monitor closely with:
Methyldopa - Bioavailability may decrease
Avoid concomitant use with:
Drugs that decrease absorption of Iron:
Antacids, e.g., Aluminum or Magnesium
Hydroxide, Calcium, Doxycycline, Food,
e.g., eggs, milk, Tetracyclines, Zinc Salts
Bisphosphonates e.g., Alendronate,
Doxycycline, Levothyroxine [administer at
least 2 hours apart], Quinolones, e.g.,
Ciprofloxacin, Tetracyclines, Zinc Salts -
Absorption of these drugs may decrease
Bisphosphonates e.g., Alendronate,
Quinolones, e.g., Ciprofloxacin,
Tetracyclines (anti-infective activity) -
Therapeutic effects of these drugs may
decrease.
Administration: Best absorbed on an empty
stomach but may be taken after food to
reduce GI adverse effects.
Dilute with water liquid preparations
containing iron salts, and if possible
swallow through a drinking straw to
prevent teeth discoloration.
Pregnancy Category: C
OTC FERROUS SALT +
FOLIC ACID
Oral: 60 mg elemental iron + 400 microgram
folic acid per tablet/ capsule/film
coated tablet
ALIMENTARY TRACT AND METABOLISM
A two-component, nutritional supplement of
iron and folic acid given during pregnancy.
Indications: Prevention of iron and folic acid
deficiencies, especially in pregnancy;
nutritional supplement during pregnancy.
NOTE: Low doses of folic acid in combination
preparations are inadequate for the
treatment of megaloblastic anemia,
overdose, and therapy with deferoxamine.
Contraindications: Hemolytic anemia;
hemochromatosis; hemosiderosis;
repeated blood transfusions of parenteral
iron therapy; pernicious anemia
Dose:
Prevention of iron and folate deficiencies in
pregnancy, by mouth, ADULT, elemental
iron, 100 mg + folic acid, 350– 400
micrograms daily (during the first
trimester, administer only in women with
low-normal hemoglobin – see
Precautions).
Severe anemia, by mouth, ADULT, elemental
iron, 120 mg + folic acid 400 micrograms
daily for 3 months; CHILD 2–12 years,
elemental iron 60 mg + folic acid, 400
micrograms daily for 3 months; CHILD <2
years, elemental iron, 25 mg + folic acid
100-400 mcg daily for 3 months
Dose Adjustments:
Renal impairment
Give iron supplementation when the patient is
anemic, and iron saturation is <20%.
Precautions:
WARNING: Iron salts can exacerbate GI
bleeding; thus, should be used with
caution in patients with GI disorders.
Transfusion-dependent anemia;
Peptic ulcer, regional enteritis, ulcerative
colitis, intestinal strictures, diverticula;
Pernicious anemia;
Elderly and children;
Pregnancy (avoid use in the first trimester;
administer only in women with low-normal
hemoglobin).
Adverse Drug Reactions:
Common: Abdominal pain, black discoloration
of feces, constipation, diarrhea,
nausea, vomiting
Less common: Black discoloration of teeth
Rare: Anaphylaxis, bronchospasm, fever, GI
erosion and perforation, hemosiderosis,
irritability, rash, sleep disturbance
Drug Interactions:
Monitor closely with:
Methyldopa: Ferrous salt may decrease its
bioavailability
Avoid concomitant use with:
Drugs that decrease absorption of Iron:
Antacids, e.g., Aluminum or Magnesium
Hydroxide, Calcium, Doxycycline, Food,
e.g., eggs, milk, Tetracyclines, Zinc Salts
Bisphosphonates e.g., Alendronate,
Doxycycline, Levothyroxine [administer at
least 2 hours apart], Quinolones, e.g.,
Ciprofloxacin, Tetracyclines, Zinc Salts:
Absorption of these drugs may decrease
Bisphosphonates e.g., Alendronate,
Quinolones, e.g., Ciprofloxacin,
Tetracyclines (anti-infective activity):
Therapeutic effects of these drugs may
decrease
Drugs that decrease the serum concentration
of Folic Acid:
Folic Acid Antagonists, e.g., Methotrexate,
Pyrimethamine, Triamterene,
Sulfonamides, Trimethoprim
Administration: To be taken on an empty
stomach, at least 1 hour before or 2 hours
after meals. Avoid taking antacids or
antibiotics within 2 hours before or after
administration.
Pregnancy Category: A
Page | 45
ALIMENTARY TRACT AND METABOLISM
GI ulceration, hyperkalemia, nausea, vomiting,
diarrhea, abdominal cramps

POTASSIUM
Drug Interactions:
Monitor closely with:
Antimuscarinics (GI adverse effects) -
POTASSIUM CHLORIDE
Rx Potassium chloride increases the risk of
adverse or toxic effects of these drugs.

Oral: 600 mg tablet Avoid concomitant use with:

750 mg durules (as chloride) (equivalent ACE Inhibitors, Potassium-containing Drugs,
to approximately 10 mEq potassium) Potassium-sparing Diuretics e.g.
1 mmol/mL syrup, 30 mL and 60 mL (as Spironolactone (hyperkalemia) - Risk of
chloride) adverse or toxic effects of these drugs
may increase
A major cation of the intracellular fluid that
Administration: Should be taken with food.
plays an active role in the conduction of
nerve impulses in the heart, brain, and
Pregnancy Category: C
skeletal muscle
ATC Code: A12BA01
Indications: Treatment and prevention of
hypokalemia

Contraindications: Hyperchloremia; severe ZINC

renal or adrenal insufficiency
GENERAL INFORMATION
Dose: An essential, mineral supplement in the diet,
Hypokalemia, prophylaxis, by mouth, ADULT, which is used as an adjunct to oral rehydration
20 mEq daily. in the treatment of acute and persistent
Hypokalemia, treatment, by mouth, ADULT, 40- diarrhea.
100 mEq daily; give in divided doses if
>20 mEq daily Indication: Adjunct to oral rehydration therapy
in acute and persistent diarrhea
Precautions:
WARNING: Monitor urine output, plasma Contraindication: Severe renal impairment
potassium, and other electrolyte
concentrations. Discontinue if severe Precaution: Acute renal failure (may
nausea, vomiting, or abdominal distress accumulate).
develops.
Adverse Drug Reactions:
Renal impairment (e.g., accumulation of Common: Diarrhea, dry mouth, dyspepsia, GI
potassium); adrenocortical insufficiency; upset, mouth irritation, nausea,
cardiac disease; acute dehydration; regurgitation, and vomiting (in children),
extensive tissue destruction. unpleasant taste
Less Common: Gastritis, headache, irritability,
Adverse Drug Reactions: lethargy, copper deficiency (with
prolonged use)

Page | 46
ALIMENTARY TRACT AND METABOLISM
Drug Interactions:
Avoid concomitant use with:
Drugs that decrease absorption of Zinc:
Calcium Salts [separate doses by 2–3
hours], Ethambutol, Ferrous Salts, Food,
e.g., milk, phytates present in cereals,
rice, corn, or legumes
Bisphosphonates e.g., Alendronate; Ferrous
Salts e.g., Ferrous sulfate; Quinolones,
e.g., Ofloxacin, Ciprofloxacin [separate
doses by at least 2 hours]; Tetracyclines
[separate administration by at least 2
hours] Decreases absorption of the
following drugs - Absorption of these
drugs may decrease.
Tetracyclines (anti-infective activity) -
Therapeutic activity of these drugs.
Administration: Tablets may be dispersed in
breastmilk, oral rehydration solution, or
water on a small spoon. Older children
may chew the tablets or swallow them
with water.
Pregnancy Category: C
ZINC
Rx
Oral: chewable tablet, (equiv. to 10 mg
elemental zinc) (as gluconate);
solution, (equiv. to 10 mg elemental
zinc/mL) drops, 15 mL, (as sulfate
monohydrate);
solution, (equiv. to 20 mg elemental
zinc/5 mL) syrup, 60 mL (as sulfate
monohydrate)
70 mg/5 mL syrup (equivalent to 10 mg
elemental zinc), 60 mL and 120 mL
(as gluconate)
An essential, mineral supplement in the diet,
which may be used as an adjunct to oral
rehydration in the treatment of acute and
persistent diarrhea.
Indications: Adjunct to oral rehydration therapy
in acute and persistent diarrhea.
Contraindications: Severe renal impairment.
Dose:
Oral rehydration therapy in acute and
persistent diarrhea (adjunct), by mouth,
CHILD 6 months-5 years, 20 mg
(elemental zinc) daily for 10-14 days;
INFANT < 6 months, 10 mg (elemental
zinc) daily for 10-14 days.
Precautions:
Acute renal failure (may accumulate).
Adverse Drug Reactions:
Common: Diarrhea, dry mouth, dyspepsia, GI
upset, mouth irritation, nausea,
regurgitation, and vomiting (in children),
unpleasant taste.
Less Common: Gastritis, headache, irritability,
lethargy.
Drug Interactions:
Avoid concomitant use with:
Bisphosphonates – reduced bisphosphonate
absorption.
Calcium salts – these may interfere with the
absorption of zinc salts (separate doses
by 2-3 hours).
Ethambutol – this may inhibit zinc absorption.
Ferrous salts – reduced absorption of zinc and
oral ferrous salts.
Food – absorption of zinc is reduced by milk,
phytates (present in cereals, rice, corn,
and legumes).
Quinolones (e.g., ofloxacin and ciprofloxacin) –
zinc binds to quinolones in the GI tract;
reducing their absorption and activity
(separate doses by at least 2 hours).
Tetracyclines – zinc forms poorly-soluble
chelates with tetracyclines, reducing their
absorption and anti-infective activity
(separate administration by at least 2
hours).
Page | 47
ALIMENTARY TRACT AND METABOLISM
Administration: Tablets may be dispersed in 23 months, 1 sachet daily, add a mixture
breast milk, in oral rehydration solution, or of micronutrients in powder form to any
in water on a small spoon; older children semisolid food.
may chew the tablets or swallow them Precautions:
with water Programs involving the use of multiple
micronutrient powders for fortification at
Pregnancy Category: C home of foods should be preceded by an
evaluation of the nutritional status among
children < 5 years of age, and existing
measures to control anemia and Vitamin
OTC MICRONUTRIENT A deficiency (e.g., hookworm control
POWDER programs, provision of supplements, use
of other products for home fortification of
foods and fortified complementary foods)
Oral: Per 1 gram sachet: to ensure that daily micronutrient needs
Vitamin A - 400 ug RE are met and not exceeded.
Vitamin C - 30 mg
Vitamin D - 5 ug
Adverse Drug Reactions:
Vitamin E - 5 mg a-TE
Common: Diarrhea
Vitamin B1 - 0.5 mg
Less common: Darkening of the stools,
Vitamin B2 - 0.5 mg
staining of child’s teeth
Vitamin B6 - 0.5 mg
Vitamin B12 - 0.9 ug
Administration: At minimum, for a period of 2
Folic acid - 150 ug
months, followed by a period of 3–4
Niacin - 6 mg
months off supplementation (so that use
Iron - 10 mg
of the micronutrient powders is started
Zinc - 4.1 mg
every 6 months).
Copper - 0.56 mg
Iodine - 90 ug
Pregnancy Category: Not available
Selenium - 17 ug

Single-dose packets of vitamins and minerals,

in powder form, which can be sprinkled
onto any ready-to-eat semi-solid food.

Indications: Prevent vitamin and mineral

deficiencies; improve iron status and
reduce anemia among infants and
children 6-23 months of age.

Contraindications: Children with specific

conditions, such as HIV infection or TB
(effects and safety of the intervention
have not been evaluated).

Dose:
Prevention of vitamin and mineral deficiencies,
improving iron status, and reducing
anemia, by mouth, CHILD and INFANT 6-

Page | 48
BLOOD AND BLOOD FORMING ORGANS
BLOOD AND BLOOD
FORMING ORGANS
ANTITHROMBOTIC AGENTS
PLATELET AGGREGATION INHIBITORS,
EXCLUDING HEPARIN
ASPIRIN
Rx
Oral: 80 mg and 100 mg tablet
An irreversible, cyclo-oxygenase (COX)
inhibitor, which inhibits platelet aggregation,
and is useful in the long-term management
and prevention of MI and stroke.
Indications: Primary prevention of acute MI
and stroke in patients with risk factors;
secondary prevention of thrombotic
cardiovascular or cerebrovascular
disease, and following bypass surgery;
acute MI; acute ischemic stroke.
Contraindications: Known hypersensitivity
(including asthma, angioedema,
urticaria, and rhinitis) to acetylsalicylic
acid and any other NSAIDs, or any
component of the formulation; children
and adolescents < 16 years (risk of
Reye’s syndrome); active peptic ulcer or
bleeding GI ulcer; bleeding disorders;
acute hemorrhagic stroke or
intracerebral bleeding; lactating
mothers.
Dose:
Prophylaxis of myocardial infarction or
cerebrovascular disease, by mouth,
ADULT, 80-100 mg once daily.
Treatment of acute MI, by mouth, ADULT, 160-
300 mg once daily.
Acute cerebral ischemic infarct, by mouth,
ADULT, 80 – 100 mg once daily (see
under Nervous System).
Transient ischemic attack (early specific
treatment), by mouth, ADULT, 50 – 320
mg once daily (see under Nervous
System).
Dose Adjustments:
Renal Impairment: For mild-to-moderate renal
impairment, dose adjustments are not
necessary; for severe impairment, the
drug is not recommended.
Hepatic Impairment: Avoid in severe liver
disease.
Precautions:
Increased risk of gastritis and GI bleeding;
asthma; urticaria; allergic disease;
uncontrolled hypertension.
Renal impairment (avoid use; due to sodium
and water retention – deterioration in
renal function may increase risk of GI
bleeding).
Hepatic impairment (avoid in severe
impairment – there is increased risk of GI
bleeding).
Elderly;
G6PD-deficiency, dehydration; gout.
Pregnancy (third trimester: impaired platelet
function and risk of hemorrhage; delayed
onset and increased duration of labor
with increased blood loss; avoid analgesic
doses, if possible, in the last few weeks;
with high doses, closure of fetal ductus
arteriosus in utero and possibly persistent
pulmonary hypertension in the newborn;
kernicterus in jaundiced neonates);
regular use of high doses could impair
platelet function and produce
hypoprothrombinemia in infants if
neonatal vitamin K stores are low;
possible risk of Reye syndrome.
Adverse Drug Reactions:
Common: Abdominal pain, asymptomatic
blood loss, back pain, bleeding time
increased, diarrhea, dyspepsia, dyspnea,
Page | 49
BLOOD AND BLOOD FORMING ORGANS
epistaxis, fatigue, GI irritation, headache,
malaise, melena, nausea, vomiting.
Less Common: Anorexia, asthenia, confusion,
dizziness, fever, flushing, gastritis, rectal
hemorrhage, hemorrhoids,
hyperglycemia, hypoglycemia (in
children), hypotension, myalgia,
palpitations, syncope, tachycardia, thirst,
tinnitus, vertigo.
Rare: Arrhythmia, convulsions, deafness,
edema, GI ulcer, and perforation,
intracranial hemorrhage, hypersensitivity
reactions, including Stevens-Johnson
syndrome; interstitial nephritis, iron-
deficiency anemia, myocarditis,
paresthesia, renal insufficiency, seizures,
thrombocytopenia, toxic epidermal
necrolysis.
Drug Interactions:
Monitor closely with:
Anticoagulant therapy (e.g., heparin, warfarin)
– increased risk of bleeding.
Corticosteroids – these may decrease
salicylate concentration when high-dose
aspirin is used; increased risk of GI
bleeding and ulceration.
Oral hypoglycemics – their hypoglycemic effect
may be increased by aspirin.
Phenytoin – its effect may be enhanced by
aspirin.
Valproic acid – its concentration is increased
by aspirin, thus increasing its therapeutic
and adverse effects; it also increases
effects on blood coagulation and platelet
function.
Avoid concomitant use with:
ACE Inhibitors (e.g., enalapril) – the
hyponatremic and hypotensive effect of
ACE inhibitors may be diminished by
aspirin; there is the risk of renal
impairment when aspirin is given in doses
of >300 mg daily.
Page | 50
Antacids (e.g., aluminum and magnesium
hydroxide) – increased excretion of
aspirin by alkaline urine.
Diuretics (e.g., spironolactone) – the
effectiveness of diuretics in patients with
underlying renal or cardiovascular
disease may be diminished due to
inhibition of renal prostaglandins.
NSAIDs (e.g., ibuprofen, naproxen) – aspirin,
even at low doses, increases the risk of
gastric ulceration with NSAIDs; these
drugs can reduce the antiplatelet activity
of low-dose aspirin and may reduce, or
negate its cardioprotective effect.
Administration: Take tablets from the
packaging just before use. Should be
taken with food, or taken immediately
after meals.
Pregnancy Category: C; D in 3rd trimester
ATC Code: B01AC06
CLOPIDOGREL
Rx
Oral: 75 mg tablet
A thienopyridine-derived, platelet aggregation
inhibitor that has no effect on
prostaglandin metabolism unlike aspirin,
and is used as an alternative for patients
who have contraindications to aspirin in
the treatment of thrombosis.
Indications: Prevention of atherothrombotic
events in peripheral arterial disease, MI,
or ischemic stroke; in acute coronary
syndrome without ST-segment elevation
(unstable angina or non-Q wave MI),
including patients undergoing stent
placement following percutaneous
coronary intervention (in combination with
aspirin); in acute MI with ST-segment
elevation, and combination with ASA in
BLOOD AND BLOOD FORMING ORGANS
medically treated patients eligible for
thrombolytic therapy; in patients with
atrial fibrillation, and for whom oral
anticoagulation is unsuitable; transient
ischemic attack and acute ischemic
cerebral infarction.
Contraindications: Known hypersensitivity to
clopidogrel or any component of the
formulation; severe liver impairment;
intracranial hemorrhage, peptic ulcer, or
other pathological bleeding;
breastfeeding.
Dose:
Acute coronary syndrome: unstable angina,
non-ST-segment elevation MI (NSTEMI),
by mouth, ADULT, 300 mg loading
dose; then 75 mg/day in combination
with aspirin 75-100 mg/day.
Acute coronary syndrome: ST-segment
elevation MI (STEMI), by mouth, ADULT,
75 mg/day (in combination with aspirin
dose at 160-320 mg/ day, and then 80-
160 mg/day).
Acute ischemic stroke and secondary
prevention of ischemic stroke, by
mouth, ADULT, 75 mg once daily (see
under Nervous System).
Coronary artery disease, by mouth, ADULT, 75
mg once daily.
Recent MI, stroke, or established peripheral
arterial disease, by mouth, ADULT, 75
mg/day.
Dose Adjustments:
Renal Impairment: The same dosage as in
patients with normal renal function may
be used in patients with mild to
moderate renal impairment; for severe
impairment, the patient should be
referred to a specialist.
Hepatic Impairment: Use with caution;
experience limited.
NOTE: CYP2C19 Inhibition and Poor
Metabolizers: Clopidogrel may be less
effective in poor metabolizers (lacking
CYP2C19). >50% of Asians have
CYP2C19 genetic variants that inhibit
clopidogrel metabolism.
Use of CYP2C19 inhibitors (Proton
Pump Inhibitors) or use in poor
metabolizers may decrease the
antiplatelet effect.
Precautions:
WARNING: Effectiveness depends on
activation to an active metabolite by
cytochrome P450 system, principally
CYP2C19). May be less effective in poor
metabolizers lacking CYP2C19. Poor
metabolizers at recommended doses
exhibit higher cardiovascular event rates
after acute coronary syndrome or
percutaneous coronary intervention.
Patients at risk of increased bleeding from
trauma, surgery, or other pathological
conditions; in patients taking medications
that increase the risk of bleeding; history
of bleeding or hemostatic disorders;
bleeding diathesis; ulcers; may need to
discontinue 5-10 days before surgical
procedure; patients allergic to aspirin who
are undergoing PCI (risk of Thrombotic
Thrombocytopenic Purpura); renal
impairment (avoid use in severe
impairment; increased risk of bleeding);
hepatic impairment; pregnancy (avoid use
if possible).
Adverse Drug Reactions:
Common: Abdominal pain, bleeding, chest
pain, depression, diarrhea, dyspepsia, flu-
like syndrome, hemorrhage, rhinitis,
upper respiratory tract infection, urinary
tract infection, urticaria.
Less Common: Constipation, dizziness,
flatulence, gastritis, GI ulcer, headache,
leukopenia, nausea, paresthesia,
pruritus, rash, vomiting.
Rare: Acute liver failure, agranulocytosis,
angioedema, aplastic anemia,
bronchospasm, colitis, confusion,
exfoliative dermatitis, hallucinations,
hepatitis, hypersensitivity-like reactions,
hypotension, interstitial pneumonitis,
Page | 51
BLOOD AND BLOOD FORMING ORGANS
lichen, myalgia, neutropenia, pancreatitis,
Stevens-Johnson syndrome, stomatitis,
thrombocytopenia, Thrombotic
thrombocytopenic purpura, vasculitis.
Drug Interactions:
NOTE: CYP2C19 enzyme metabolizes
clopidogrel to its active metabolite.
Consequently, combining clopidogrel with
inhibitors of CYP2C19 (see Appendix) may
decrease its efficacy.
Monitor closely with:
Anticoagulants (e.g., warfarin) – combination
use increases the risk of bleeding.
Aspirin – this may cause unusual bleeding,
severe abdominal pain, weakness, and
the appearance of black stools.
Atorvastatin – may reduce the efficacy of
clopidogrel, resulting in blood clots.
Carbamazepine – increases level or effects of
clopidogrel.
Clarithromycin, erythromycin – decrease the
level or effects of clopidogrel.
Drugs that can affect the clotting process (e.g.
NSAIDs, anticoagulants, and other
antiplatelets) – clopidogrel inhibits
platelet aggregation; increased risk of
bleeding when the drug is used with the
stated drugs.
Isoniazid – decreases effects of clopidogrel.
Rifampin – increases level and effects of
clopidogrel.
Avoid concomitant use with:
Proton pump inhibitors (e.g., omeprazole,
esomeprazole) –may reduce the antiplatelet
activity of clopidogrel by reducing the
formation of its active metabolite; decreasing
its effectiveness in reducing the risk of
cardiovascular events.
Administration: May be taken with or without
food.
Pregnancy Category: B
Page | 52
ATC Code: B01AC04
ANTIHEMORRHAGICS
ANTIFIBRINOLYTICS
TRANEXAMIC ACID
Rx
Oral: 250 mg and 500 mg capsule
An anti-fibrinolytic agent, which is a
competitive inhibitor of plasminogen activity.
Indications: For the treatment and control of
excessive bleeding in various medical,
and surgical, obstetric and gynecologic,
and dental conditions.
NOTE: Medical conditions include: epistaxis,
hemoptysis, hematuria, peptic ulcer
disease with hemorrhage, blood
dyscrasias with hemorrhage. Obstetric
and gynecologic conditions include
menorrhagia, menometrorrhagia, post-
partum hemorrhage, and bleeding
following abortion. Dental conditions
include bleeding following tooth
extraction and dental surgery.
Contraindications: Hypersensitivity to
tranexamic acid or any component of
the formulation; patients with a history
or risk of thrombosis, unless
concomitant treatment with
anticoagulants; active thromboembolic
disease, such as deep vein thrombosis,
pulmonary embolism, and cerebral
thrombosis; patients with acquired
disturbances of color vision (if
disturbances of color vision arise during
treatment, discontinue the drug).
BLOOD AND BLOOD FORMING ORGANS
Dose:
Menorrhagia/ Menometrorrhagia, by mouth,
ADULT, 1-1.5 g every 6 to 8 hours for 3
to 4 days (maximum, 4 g daily).
Dental surgery, by mouth, ADULT, 25 mg/kg 2
hours before surgery, then 25 mg/kg 3
or 4 times daily for 6-8 days.
Epistaxis, by mouth, ADULT, 1.5 g every 8
hours for 4 to 10 days.
Gastrointestinal hemorrhage, ADULT, following
a maximum of 3 days of intravenous
dose of 1 g every 4 hours, tranexamic
acid is given by mouth, 1.5 g every 6
hours for a maximum of 4 days.
Hematuria, by mouth, ADULT, 1 to 1.5 g orally
every 8 to 12 hours daily until
macroscopic hematuria is no longer
present (see Precautions below).
Dose Adjustments:
Children: Tranexamic acid has limited use in
children and only limited data is
available on dosing.
Elderly: No dosage reduction is necessary
unless there is evidence of renal failure.
Renal Impairment: Reduce dose in patients
with renal insufficiency (because of risk
of drug accumulation).
Precautions:
For patients on prolonged treatment with
tranexamic acid, perform an
ophthalmological examination (including
visual acuity, color vision, eyeground, and
visual fields) before and at regular
intervals during treatment; discontinue if
changes are found; focal areas of retinal
degeneration have developed in animal
studies at doses 3-40 times the
recommended human dose.
Treatment with tranexamic is not indicated in
hematuria caused by diseases of the
renal parenchyma; (intravascular
precipitation of fibrin frequently occurs
and may aggravate the disease.
Furthermore, antifibrinolytic treatment
carries the risk of clot retention in the
renal pelvis in cases of massive renal
hemorrhage of any cause).
Patients with a high risk for thrombosis
(previous thromboembolic event and
family history of thromboembolic disease)
should use tranexamic acid only if there is
a strong medical indication and under
strict medical supervision (there are
reports of venous and arterial thrombosis
or thromboembolism in patients given
tranexamic acid and cases of central
retinal artery and central retinal vein
obstruction; patients taking tranexamic
acid developed intracranial thrombosis;
however, further observation is needed).
Urinary tract obstruction due to clot formations
in patients with severe bleeding from the
upper urinary tract.
Patients with irregular menstrual bleeding
should not use tranexamic acid until the
cause of irregular bleeding has been
established. Consider an alternative
treatment if menstrual bleeding is not
adequately reduced by tranexamic acid.
Indissoluble clots may develop in body cavities,
such as pleural space, joint spaces, and
urinary tract (e.g., renal pelvis, bladder)
due to extravascular clots, which may be
resistant to physiologic fibrinolysis.
Pregnancy (there are no adequate and well-
controlled studies; however, tranexamic
acid crosses the placenta and appears in
cord blood; use only if needed); lactation
(present in breast milk at 1% of the
corresponding serum levels; exercise
caution when administering to
breastfeeding women); use in children
(has had limited use in children,
principally in tooth extraction).
Adverse Drug Reactions:
Common: Abdominal pain, anemia, arthralgia,
back pain, diarrhea, fatigue, headache,
muscle cramps and spasms, nausea,
nasal and sinus symptoms, vomiting.
Rare: Allergic skin reactions, diarrhea, hyper-
sensitivity reactions, hypotension,
thrombosis, thromboembolic events (e.g.,
deep vein thrombosis, pulmonary
Page | 53
BLOOD AND BLOOD FORMING ORGANS
embolism); transient disturbance of color Ferrous sulfate, desiccated –
vision. 32%

Drug Interactions: An essential trace element required for the

Monitor closely with:
Fibrinolytic preparations – tranexamic acid
may counteract their thrombolytic effect.
Avoid concomitant use with:
Contraceptives (estrogens and progestins) –
may enhance the thrombogenic effect of
tranexamic acid; increased the risk of
thromboembolic events.
Administration: May be taken with or without
food. Capsules must be swallowed whole;
do not chew, break, or crush.
formation of hemoglobin and the efficient
oxygen transport in the blood.
Indications: Treatment of iron-deficiency
anemia and supplement and prophylaxis
in people on hemodialysis receiving
erythropoietin.
Contraindications: Anemia not due to iron
deficiency; parenteral iron therapy; in
patients receiving repeated blood
transfusions; hemochromatosis;
hemosiderosis

Pregnancy Category: B Dose:

Prevention of iron and folate deficiencies in
ATC Code: B02AA02 pregnancy, by mouth, ADULT, 1 - 2
tablets daily throughout pregnancy.
Severe anemia, by mouth, ADULT, give 2
ANTIANEMIC PREPARATIONS tablets of the above preparation daily
for 3 months; or, elemental iron, 120
mg + folic acid 400 mcg daily for 3
IRON PREPARATIONS months; CHILD 2–12 years, 1 tablet of
the above preparation (elemental iron
60 mg + folic acid, 400 micrograms)
OTC FERROUS SALT daily for 3 months; CHILD <2 years,
elemental iron, 25 mg + folic acid 100-
400 mcg daily for 3 months
Oral: tablet, (equiv. to 60 mg elemental iron)
solution, (equiv. to 15 mg elemental NOTE: For women and children > 5 years of
iron/0.6 mL) age, folic acid may also be given.
drops, 15 mL and 30 mL
solution, (equiv. to 30 mg elemental See Ferrous Salt under Mineral Supplements
iron/5 mL) in Chapter 1: Alimentary Tract and Metabolism
syrup, 60 mL for other information.

N.B.: The elemental iron content of a

ferrous salt depends on the type of
preparation as follows:
Ferrous fumarate – 33%
Ferrous gluconate – 12%
Ferrous lactate – 19%
Ferrous sulfate, hydrated – 20%

Page | 54
BLOOD AND BLOOD FORMING ORGANS
FOLIC ACID AND ITS DERIVATIVES
OTC FERROUS SALT +
FOLIC ACID
Oral: 60 mg elemental iron + 400 microgram
folic acid per tablet/ capsule/film
coated tablet
A two-component, nutritional supplement of
iron and folic acid is given during
pregnancy.
Indications: Prevention of iron and folic acid
deficiencies, especially in pregnancy;
nutritional supplement during pregnancy.
Contraindications: hemolytic anemia;
hemochromatosis; hemosiderosis;
pernicious anemia; repeated blood
transfusions or parenteral iron therapy.
Administration: To be taken on an empty
stomach, at least 1 hour before or 2 hours
after meals. Avoid taking antacids or
antibiotics within 2 hours before or after
administration.
See Ferrous Salt + Folic Acid under Mineral
Supplements in Chapter 1: Alimentary Tract
and Metabolism for other information.
Pregnancy Category: A
ATC Code: B03BB51
OTC FOLIC ACID
Oral: 400 mcg, 800 mcg, 1 mg and 5 mg
tablet /capsule
2.5 mg/mL pediatric drops
5 mg/5 mL syrup
Also known as Vitamin B9, it is reduced in the
body to tetrahydrofolate, which is a
coenzyme for various metabolic
processes, including the synthesis of
purine and pyrimidine nucleotides, and
hence in the synthesis of DNA. It is also
involved in some amino acid conversions
and the formation and utilization of
formate. Folic acid is also used in women
of childbearing potential and pregnant
women to protect against neural tube
defects in their offspring.
Indications: Treatment of megaloblastic and
macrocytic anemias due to folate
deficiency; used for diarrhea in pediatric
patients.
Contraindications: Hypersensitivity to folic acid
or any component of the formulation.
Dose:
Anemia, by mouth, ADULT, 0.4 mg daily;
PREGNANT AND LACTATING WOMEN, 0.8
mg daily; CHILD <4 years up to 0.3 mg
daily; INFANT 0.1 mg daily
See Folic Acid under Vitamins in Chapter 1:
Alimentary Tract and Metabolism for other
information.
Pregnancy Category: A
ATC Code: B03BB01
Page | 55
BLOOD AND BLOOD FORMING ORGANS
Cardiovascular condition, cirrhotic disease,
BLOOD SUBSTITUTES AND and nephrotic disease, and in patients
PERFUSION SOLUTIONS receiving corticosteroid therapy; Solutions
containing dextrose should be used with
caution in patients with overt or known
IV SOLUTIONS AFFECTING THE diabetes mellitus and carbohydrate
ELECTROLYTE BALANCE intolerance for any reason; clinical
evaluation and periodic laboratory
DEXTROSE PREPARATIONS IN SODIUM examinations are necessary;
Cardiovascular effects.
CHLORIDE
Drug Interactions:
General Information
Monitor closely with:
Sterile preparations containing dextrose for
Corticosteroids –The risk of hypertension and
intravenous (IV) administration.
edema may increase because of sodium
and water retention.
Contraindications: Known hypersensitivity to
corn or corn products; and where the
Administration: Adjust the rate of
administration of sodium or chloride could
administration according to the
be clinically detrimental.
recommended rate. Too rapid infusion of
hypertonic solutions may cause local pain
Dose:
and venous irritation. Inspect visually for
The dose is dependent on the age, weight, and
particulate matter and discoloration
clinical condition of the patient. Select
before administration. Do NOT administer
dose and constant infusion rate with
unless the solution is clear, and the
caution in pediatric patients, particularly
container is undamaged.
neonates and low birth weight infants,
because of the increased risk of
hyperglycemia or hypoglycemia.
Dose of sodium chloride is dependent on the
5% DEXTROSE IN 0.9%
degree of sodium depletion (e.g., Rx SODIUM CHLORIDE
moderately severe hyponatremia where
serum sodium is 125–129 mmol/L, or
profound hyponatremia where serum Inj: 250 mL, 500 mL and 1 L bottle/bag (IV
sodium is <125 mmol/L); on the severity infusion)
of symptoms; and time of development of
hyponatremia (e.g., acute, where Composition:
hyponatremia is documented to exist <48 Dextrose — 50 g/L
hours). Na+ — 154 mmol/L
Cl‐ — 154 mmol/L
Dose Adjustment:
Renal Impairment: Take care in dose selection A sterile, non-pyrogenic, large-volume
due to an increased risk of adverse parenteral solution, which contains 0.9%
effects. of sodium chloride and 5% dextrose in
water for injection; a source of
Precautions: electrolytes, water, and calories for
WARNING: Mix infusion solutions thoroughly patients.
after adding concentrated electrolytes to
avoid possible toxicity.

Page | 56
BLOOD AND BLOOD FORMING ORGANS
Indications: Initial fluid and electrolyte
replacement therapy in conditions with
combined water and sodium depletion; a
vehicle for IV drug administration.
Adverse Drug Reactions:
Rare: Sodium accumulation, water retention
See General Information on Dextrose
Preparations in Sodium Chloride under I.V.
Solutions affecting the Electrolyte Balance in
Chapter 02: Blood and Blood Forming Organs
for other information.
Pregnancy Category: C
ATC Code: B05BB02
5% DEXTROSE IN
Rx LACTATED RINGER’S
Inj: 250 mL, 500 mL and 1 L bottle/bag (IV
infusion)
Composition:
Dextrose — 50 g/L
Na+ — 130 mmol/L
K+ — 4 mmol/L
Ca++ — 1.22 – 1.5 mmol/L
Cl‐ — 109 mmol/L
Lactate — 28 mmol/L
A sterile, non-pyrogenic solution, which
contains 5% dextrose and Lactated
Ringer’s solution, in a single-dose
container for IV administration and can
produce a metabolic alkalinizing effect.
Indications: Source of water, electrolytes, and
calories; alkalinizing effect.
NOTE: Capable of inducing diuresis depending
on the clinical condition of the patient.
NOT for use in the treatment of severe
potassium deficiency, lactic acidosis, or
severe metabolic acidosis.
Contraindications: Known hypersensitivity to
sodium lactate; allergy to corn or corn
products.
Dose:
The dose is dependent on the age, weight, and
clinical condition of the patient.
Dose Adjustments:
Geriatric: Start at the low end of the dosing
range, reflecting the greater frequency of
decreased hepatic, renal, or cardiac
function, and concomitant disease or drug
therapy.
Renal and Hepatic Impairment: Select dose
with care due to increased risk of adverse
effects, e.g., sodium and potassium
retention.
Precautions:
WARNING: Mix infusion solutions
thoroughly after adding concentrated
electrolytes to avoid possible toxicity.
Hypersensitivity (immediately stop infusion if
any signs or symptoms of a suspected
hypersensitivity reaction develop);
Electrolyte imbalance;
Hyperkalemia or conditions predisposing to
hyperkalemia; alkalosis or risk for
alkalosis;
Conditions that may cause sodium and/or
potassium retention, fluid overload, or
edema;
Cardiac disease; hypervolemia; overhydration;
Impaired glucose tolerance or diabetes
mellitus;
Severe renal impairment;
Conditions associated with increased lactate
levels or impaired lactate utilization, such
as severe hepatic insufficiency;
Substantially hypertonic solutions (administer
hyperosmolar solutions with caution, if at
all, to patients with hyperosmolar states);
Solutions containing calcium salts should be
used with caution in patients with
hypercalcemia or conditions predisposing
Page | 57
BLOOD AND BLOOD FORMING ORGANS
to hypercalcemia, such as severe renal adverse or toxic effects of these drugs
impairment and granulomatous diseases may be increased.
associated with increased calcitriol
synthesis such as sarcoidosis, calcium Administration: Administer via IV route
renal calculi;
Elderly; children and newborns Inspect visually for particulate matter and
discoloration before administration.
Adverse Drug Reactions:
Less Common: Pain and inflammation at the Do NOT administer unless solution is clear, and
injection site, phlebitis, tissue necrosis, container is undamaged.
venous irritation, venous thrombosis.
Rare: Angioedema, anxiety, blood pressure Do NOT connect flexible plastic containers in
decreased, bronchospasm, chest series to avoid air embolism due to
discomfort and pain, cough, decreased possible residual air contained in the
heart rate, dysgeusia, dyspnea, edema, primary container. Pressurizing IV
erythema, flushing, headache, solutions contained in flexible plastic
hyperkalemia, hypersensitivity reactions, containers to increase flow rates can
including anaphylactic and anaphylactoid result in air embolism if the residual air in
reactions; hypesthesia, nausea, the container is not fully evacuated prior
paresthesia, pruritus, pyrexia, rash, to administration.
respiratory distress, tachycardia, throat
irritation, urticaria. Do NOT administer simultaneously with citrate
anticoagulated or preserved blood
Drug Interactions: through the same administration set to
Monitor closely with: prevent likelihood of coagulation.
Acidic Drugs, e.g., Salicylates, Barbiturates
(increased renal clearance); Basic Pregnancy Category: C
Drugs, e.g., Sympathomimetics
(decreased renal clearance); Lithium ATC Code: B05BB02
(increased renal clearance) – Renal
clearance of these drugs can be
altered.
Corticosteroids (sodium and fluid retention):
The risk of hypertension and edema
may increase due to sodium and water
retention
Drugs that can cause hyperkalemia, e.g.,
Potassium-sparing Diuretics,
Angiotensin II Receptor Antagonists,
ACE Inhibitors, Immunosuppressants
(hyperkalemia) Thiazide Diuretics
(hypercalcemia) Vitamin D
(hypercalcemia) – Risk of adverse or
toxic effects can be increased.

Avoid concomitant use with:

Ceftriaxone (Ceftriaxone-Calcium Salt
precipitation in the bloodstream):

Page | 58
BLOOD AND BLOOD FORMING ORGANS
WARNING: Mix infusion solutions
BALANCED MULTIPLE thoroughly after adding concentrated
Rx MAINTENANCE SOLUTON electrolytes to avoid possible toxicity.

Hypersensitivity reactions; CHF; renal

Inj: with 5% dextrose, 250 mL and 500 mL insufficiency; clinical states with edema
(infants) and 1 L (children and adults) with sodium retention.
bottle/bag (IV infusion) Administration of the solution can cause fluid
and/or solute overloading resulting in
Composition: dilution of serum electrolyte
Preparation Preparation concentration, overhydration, congested
for Infants for states, or pulmonary edema; Clinical
Children/ evaluation and periodical laboratory
Adults determinations are necessary to monitor
Dextrose 50 g/L 50 g/L changes in fluid balance, electrolyte
Na+ 25-30 40-50 mmol/L concentration, and acid-base balance
mmol/L during prolonged therapy or whenever the
K+ 20-25 13-30 mmol/L patient’s condition warrants such
mmol/L evaluation.
Mg++ 1.35- 1.65 mmol/L
1.65 Adverse Drug Reactions:
mmol/L
Cl- 22 40 mmol/L Febrile response, infection at the site of
mmol/L injection, venous thrombosis or phlebitis
Acetate 23 16 mmol/L extending from the site of injection,
mmol/L extravasation, hypervolemia

A sterile, nonpyrogenic, hypertonic solution of
balanced maintenance electrolytes and
5% dextrose injection in water for
injection.
Indications: Fluid and electrolyte maintenance
therapy
Contraindications: Hyperkalemia; oligo-anuric
renal failure.
NOTE: Above may occur because of the
solution or the technique during
administration.
Drug Interactions: No information available
NOTE: Additives may be incompatible. Consult
with pharmacist.
Administration:

Dose: Administer by IV infusion.

The dose is dependent on the age, weight, and
degree of fluid and electrolyte loss.
Dose Adjustments:
Renal impairment: Select doses with care due
to an increased risk of adverse effects,
e.g., sodium and potassium retention.
Precautions:
Contains no bacteriostat, antimicrobial agent,
or added buffer and is intended only for
use as a single-dose injection. Discard
unused portions.
When introducing additives, use aseptic
technique, mix thoroughly, and do not
store.

Page | 59
BLOOD AND BLOOD FORMING ORGANS
Select dose and constant infusion rate of IV Precautions:
dextrose with caution in pediatric WARNING: Mix infusion solutions thoroughly
patients, particularly neonates and low after adding concentrated electrolytes to
birth weight infants, because of the avoid possible toxicity.
increased risk of hyperglycemia or
hypoglycemia. Hypersensitivity reactions; CHF; renal
insufficiency; clinical states with edema
Pregnancy Category: C with sodium retention; Administration of
the solution can cause fluid and/or solute
ATC Code: B05BB02 overloading resulting in dilution of serum
electrolyte concentration, overhydration,
congested states, or pulmonary edema;
Clinical evaluation and periodical
BALANCED MULTIPLE laboratory determinations are necessary
Rx REPLACEMENT SOLUTON to monitor changes in fluid balance,
electrolyte concentration, and acid-base
balance during prolonged therapy or
Inj: 500 mL and 1 L bottle/bag (IV infusion) whenever the patient’s condition warrants
such evaluation.
Composition:
Na+ — 140-145 mmol/L Adverse Drug Reactions:
K+ — 4-5 mmol/L
Mg++ — 1-1.65 mmol/L Febrile response, infection at the site of
Cl‐ — 98-127 mmol/L injection, venous thrombosis or phlebitis
Acetate — 24-50 mmol/L extending from the site of injection,
Plus 5% dextrose (50 g/L) extravasation, hypervolemia

A sterile, non-pyrogenic solution consisting of NOTE: Above may occur because of the
balanced electrolytes with 5% dextrose in solution or the technique during
water for injection. administration.

Indications: Acute fluid and electrolyte Drug Interactions:

replacement therapy; fluid replacement in Monitor closely with:
hyperchloremic acidosis. Corticosteroids e.g. prednisone - Increased risk
of hypertension and edema due to sodium
Contraindications: Not to be used for fluid and and water retention.
electrolyte maintenance therapy;
hyperkalemia, hypermagnesemia; Administration:
metabolic alkalosis. Administer by IV infusion.
Inspect visually for particulate matter and
Dose: discoloration before administration. Do
The dose is dependent on age, weight, and NOT administer unless the solution is
degree of fluid and electrolyte loss. clear, and the container is undamaged.

Dose Adjustments: Pregnancy Category: C

Renal impairment: Select doses with care due
to an increased risk of adverse effects, ATC Code: B05BB02
e.g., sodium and potassium retention.
IV SOLUTIONS ADDITIVES
Page | 60
BLOOD AND BLOOD FORMING ORGANS
0.9% SODIUM
Rx CHLORIDE
Inj: 2 mL, 2.5 mL, 5 mL, 10 mL and 20 mL
ampul
50 mL, 100 mL, 200 mL, 500 mL and 1
bottle/bag (IV infusion)
Composition:
Na+ — 154 mmol/L
Cl‐ — 154 mmol/L
A sterile, non-pyrogenic, isotonic solution of
sodium chloride in water for injection.
Indications: Fluid and electrolyte replacement
therapy in conditions where water and
sodium losses are in isotonic proportion;
a vehicle for IV drug administration;
lavage in surgical patients.
Contraindications: Where the administration of
sodium or chloride could be clinically
detrimental.
Dose:
NOTE: Individualize fluid administration based
on calculated maintenance or
replacement fluid requirements.
Fluid and electrolyte replacement, by IV
infusion, ADULT, and CHILD, determined
based on clinical and, whenever possible,
electrolyte monitoring.
Dose of sodium chloride is dependent on the
degree of sodium depletion (i.e.,
moderately severe hyponatremia where
serum sodium is between 125-129
mmol/L, or profound hyponatremia where
serum sodium is <125 mmol/L); on the
severity of symptoms (i.e., moderately or
severely symptomatic); and on time of
development of hyponatremia (e.g., acute
where hyponatremia is documented to
exist <48hrs).
IMPORTANT NOTE: Sodium deficit must be
corrected gradually in stages. Avoid
overtly rapid correction to prevent the
development of Osmotic Demyelination
Syndrome (previously named Central
Pontine Myelinolysis). The rate of
correction of hyponatremia should not be
more than 10 mmol/L (or 10 mEq/L) in
24 hours, or 18 mmol/L (or 10 mEq/L) in
48 hours.
Dose Adjustments:
Renal impairment: Select doses with care due
to an increased risk of adverse effects.
Precautions:
WARNING: Mix infusion solutions
thoroughly after adding concentrated
electrolytes to avoid possible toxicity.
Impaired renal function, cardiac failure,
hypertension, peripheral and pulmonary
edema, and toxemia during pregnancy
(restrict intake); Cardiac, cirrhotic, or
nephrotic patients.
Adverse Drug Reactions:
Air embolization, febrile response, local
tenderness, tissue necrosis or infection at
the site of injection, venous thrombosis or
phlebitis extending from the site of
injection, extravasation, hypervolemia
NOTE: May occur because of the solution,
added drugs, or the technique of
reconstitution or administration.
Rare: Edema, sodium accumulation
Drug Interactions:
Monitor closely with:
Corticosteroids e.g. prednisone - Increased risk
of hypertension and edema due to sodium
and water retention.
Administration:
For single use only.
Contamination may lead to injury, illness, or
death. Inspect visually for particulate
Page | 61
BLOOD AND BLOOD FORMING ORGANS
matter and discoloration before
administration.
Pregnancy Category: C
ATC Code: B05XA03
5% DEXTROSE IN WATER
Rx
Inj: 250 mL (IV infusion and as a vehicle for
IV medications)
A sterile, non-pyrogenic solution of dextrose
that is indicated for use in adults and
children as a source of calories and water
of hydration.
Indications: Replacement therapy in conditions
mainly due to water losses; elevated
serum sodium; IV infusion to keep vein
open for IV drug administration.
Contraindications: Known hypersensitivity to
corn or corn products.
Dose:
For replacement therapy, by IV infusion,
depending on the requirement.
Dose Adjustments:
Renal Impairment: Select doses with care due
to an increased risk of adverse effects.
Precautions:
WARNING: Mix infusion solutions
thoroughly after adding concentrated
electrolytes to avoid possible toxicity.
Fluid and/or solute overload; prolonged
infusion of isotonic or hypotonic dextrose
in water; hyponatremia; fluid retention;
DM or carbohydrate intolerance (use with
caution); Contains aluminum which may
be toxic, particularly in those with
Page | 62
impaired kidney function, e.g., premature
neonates.
Adverse Drug Reactions:
Febrile response, infection at the site of
injection, venous thrombosis or phlebitis
extending from the site of injection,
extravasation, hypervolemia.
NOTE: May occur because of the solution or the
technique during administration.
Drug Interactions: No information was found
Administration:
Adjust the rate of administration according to
the recommendation. Too rapid infusion
may cause local pain and venous
irritation. Use the largest peripheral vein
and a small-bore needle. Inspect visually
for particulate matter and discoloration
before administration.
Pregnancy Category: C
ATC Code: Not available
CALCIUM GLUCONATE
Rx
Inj: 10%, 10 mL ampul/vial (IV)
10%, 20 mL and 25 mL bottle (IV)
An organic Calcium salt used to prevent or treat
negative calcium balance. It also helps
facilitate nerve and muscle performance
as well as normal cardiac function.
Indications: Treatment of acute magnesium
toxicity seen in the obstetric setting in
patients receiving magnesium sulfate for
eclampsia (for primary health facilities
with BeMONC and also the CEmONC
units).
NOTE: In this situation, magnesium
BLOOD AND BLOOD FORMING ORGANS
toxicity can present as follows: depressed patient should remain recumbent for a
deep tendon reflexes, cardiopulmonary short time
arrest, and respiratory depression. The
toxicity arises from the blockage of Visually inspect parenteral products for
calcium and potassium channels due to particulate matter and discoloration
magnesium. Calcium gluconate treats before administration.
hypermagnesemia by directly
antagonizing magnesium at the Close monitoring of serum calcium
neuromuscular junction. concentrations is essential during IV
administration of calcium.
Contraindications: Ventricular fibrillation;
metastatic bone disease; injection into Oral administration of calcium
myocardium; renal calculi; hypercalcemia supplements or calcium-rich foods should
and predisposition to hypercalcemia (e.g., replace IV calcium therapy as soon as
hyperparathyroidism, certain possible.
malignancies); above normal serum
calcium levels; concomitant NOTE: Do NOT administer by IM or SC
administration of ceftriaxone in neonates. route.

Dose: Closely monitor serum calcium

NOTE: 1 g calcium gluconate = 90 mg (4.5 concentrations during IV administration of
mEq, 9.3%) elemental calcium. calcium.

Hypermagnesemia, by IV administration, Oral administration of calcium

ADULT, 1,000– 2,000 mg (10–20 mL) supplements or calcium-rich foods should
single dose at a rate not exceeding replace IV calcium therapy as soon as
0.5–2 mL/minute in symptomatic possible
hypermagnesemia.
If with cardiac toxicity due to ATC Code: A12AA03
hypermagnesemia, the following is
given: 10% solution, 15 to 30 mL slow
IV over 2 to 5 minutes during cardiac
arrest from hypermagnesemia. GLUCOSE (DEXTROSE)
Rx
Precautions:
Impaired renal function; cardiac disease; Inj: 50%, 50 mL vial (IV)
hypercalcemia-associated diseases, e.g.,
sarcoidosis. A sterile, hypertonic solution of glucose, which
Lactation (excreted in breastmilk; use with provides a source of calories in a minimal
caution). volume of water and is used in restoring
blood glucose concentrations in the
Administration: Administer by slow IV injection treatment of hypoglycemia.
as a 10% solution slowly through a small
needle into a large vein to avoid a too Indications:
rapid increase in serum calcium and Fluid replacement without significant
extravasation of calcium solution into the electrolyte deficit; management of severe
surrounding tissue that may lead to tissue hypoglycemia in an adult who is unable to
necrosis. Following IV injection, the take oral food or fluids.

Page | 63
BLOOD AND BLOOD FORMING ORGANS
Contraindications:
Hyperglycemia; use of hyperosmotic solutions
in patients with anuria; diabetic coma;
glucose-galactose malabsorption
syndrome; dehydrated patients with
delirium; intracranial or intraspinal
hemorrhage; should not be used after
ischemic attacks.
Dose:
Fluid replacement, by IV infusion, ADULT, and
CHILD, determined based on clinical data
and, whenever possible, electrolyte
monitoring.
Treatment of hypoglycemia, by IV infusion
(50% glucose solution into a large vein),
ADULT, 25-50 mL.
Dose adjustments:
Renal Impairment: Select doses with care.
Precautions:
Hypertonic solutions of glucose should be
administered via a large central vein (to
minimize damage at the site of injection,
e.g., thrombophlebitis); diabetes mellitus
(may require additional insulin); glucose
solutions should be used with caution in
patients with overt or known subclinical
DM, carbohydrate intolerance for any
reason, severe undernutrition, thiamine
deficiency, hemodilution, sepsis, trauma,
hypophosphatemia, shock, metabolic
acidosis or severe dehydration; rapid
administration of hypertonic glucose
solutions may produce substantial
hyperglycemia and hyperosmolar
syndrome; patients should be observed
for signs of mental confusion and loss of
consciousness, especially those patients
with chronic uremia or carbohydrate
intolerance; prolonged use in parenteral
nutrition may affect insulin production
(blood and urine glucose should be
monitored); IV administration of glucose
may result in hypophosphatemia,
hypokalemia, and hypomagnesemia.
Page | 64
Do not administer glucose solutions through
the same infusion equipment as whole
blood since hemolysis and clumping may
occur.
Pregnancy (may result in fetal insulin
production, with an associated risk of
rebound hypoglycemia in the neonate).
Adverse Drug Reactions:
NOTE: The administration of glucose without
adequate thiamine levels may precipitate
overt deficiency states e.g., Wernicke's
encephalopathy.
Less Common: Pain at the injection site,
phlebitis, tissue necrosis, venous
irritation, venous thrombosis.
Rare: Dehydration, edema or water
intoxication, fluid, and electrolyte
imbalance, glycosuria, hyperglycemia,
hypokalemia, hypomagnesemia,
hypophosphatemia.
Drug Interactions:
Monitor closely with:
Magnesium salts – associated with lower
fasting glucose and insulin.
Administration: Should be administered via a
large vein (e.g., into a secure IV cannula in
an antecubital vein).
Do not administer glucose solutions
through the same infusion equipment as
whole blood since hemolysis and
clumping may occur.
NOTE: Parenteral drug products should be
inspected visually for particulate matter
and discoloration before administration,
whenever solution and container permit
Pregnancy Category: C
ATC Code: Not available
BLOOD AND BLOOD FORMING ORGANS
LACTATED RINGER’S
Rx SOLUTION
Inj.: 500 mL and 1 L bottle / bag (IV
infusion)
Composition:
Na+ - 130 mmol/L
K+ - 4 mmol/L
Ca++ - 1.22 – 1.5 mmol/L
Cl- - 109 mmol/L
Lactate - 28 mmol/L
A sterile, non-pyrogenic, lactate-containing
solution, which serves as a source of
hydration and electrolytes and produces a
metabolic alkalinizing effect.
Indications: Fluid and electrolyte replacement
therapy in the presence of acidosis; IV
infusion in the initial management of the
injured or wounded; hypovolemic shock
Contraindications: Metabolic and respiratory
alkalosis; hypocalcemia; hypochlorhydria;
lactic acidosis; anuria; oliguria;
hyperkalemia; increased BUN; cardiac
failure.
Dose: Dose is dependent on age, weight, and
the clinical condition of the patient.
Dose Adjustment:
Renal Impairment: Select dose with care due
to an increased risk of adverse effects,
e.g., sodium and potassium retention.
Precautions:
WARNING: Mix infusion solutions
thoroughly after adding concentrated
electrolytes to avoid possible toxicity.
Avoid simultaneous administration with blood;
hyperkalemia; hypernatremia;
hyperchloremia; cardiac diseases;
alkalosis; increased blood glucose; hepatic
impairment; conditions which may cause
potassium or sodium retention, fluid
overload or edema, e.g., renal impairment,
hypervolemia, overhydration; There is a
risk for hyponatremia due to lower sodium
content compared to 0.9% NaCl or
Balanced Multiple Replacement Solution.
Adverse Drug Reactions:
Less Common: Pain and inflammation at the
injection site, phlebitis, tissue necrosis,
venous irritation, venous thrombosis.
Rare: Angioedema, anxiety, blood pressure
decreased, bronchospasm, chest
discomfort and pain, cough, decreased
heart rate, dysgeusia, dyspnea, edema,
erythema, flushing, headache,
hyperkalemia, hypersensitivity reactions,
including anaphylactic and anaphylactoid
reactions; hypesthesia, nausea,
paresthesia, pruritus, pyrexia, rash,
respiratory distress, tachycardia, throat
irritation, urticaria.
Drug Interactions:
Monitor closely with:
Acidic Drugs, e.g., Salicylates, Barbiturates;
Lithium – Their renal clearance will be
increased
Basic Drugs, e.g., Sympathomimetics – Their
renal clearance will be decreased.
Drugs that can cause hyperkalemia, e.g.,
Potassium-sparing Diuretics, Angiotensin II
Receptor Antagonists, ACE Inhibitors,
Immunosuppressants – Their risk of
causing hyperkalemia may increase.
Thiazide Diuretics, Vitamin D – Their risk of
causing hypercalcemia may increase.
Avoid concomitant use with:
Ceftriaxone – With an increased risk of adverse
or toxic effects. (Ceftriaxone-Calcium salt
precipitation in the bloodstream)
Administration: For IV administration.
Inspect visually for particulate matter and
discoloration. Use only if the solution is
clear and seal intact.
Page | 65
BLOOD AND BLOOD FORMING ORGANS
Pregnancy Category: C
ATC Code: B05XA30
MAGNESIUM SULFATE
Rx
Inj: 250 mg/mL, 2 mL and 10 mL ampul
(IM, IV)
250 mg/mL, 20 mL vial (IV)
500 mg/mL, 2 mL and 10 mL ampul
(IM, IV)
A sterile preparation that contains magnesium
as heptahydrate.
Indications:
For prevention of seizures in women with
severe preeclampsia, and for controlling
seizures and preventing their recurrence
in eclamptic patients.
Contraindications:
Heart block; myocardial infarction;
hypermagnesemia; deranged renal
function; myasthenia gravis; IV use for
preeclampsia or eclampsia during the 2
hours before delivery.
Dose:
Control and prevention of recurrent seizures in
eclamptic patients: IV loading dose of 4
grams over 5 – 15 minutes followed by
maintenance IV infusion of 1g/hour for at
least 24 hours after the last seizure or
delivery (whichever occurs later); or, by
deep IM injection (used for special
situations when IV lines are not available)
5 g into each buttock, then 5 g every 4
hours into alternate buttock for at least 24
hours after the last seizure or delivery.
A recurrent seizure should be treated by
further IV bolus of 2 g; 4 g if bodyweight is
over 70 kg).
Page | 66
NOTE: If seizures persist despite treatment
with magnesium sulfate, hospitalize the
patient and consider other pre-hospital
options that include diazepam.
Dose adjustments:
Renal Impairment
Reduce dose. Up to 50% of an IV dose may be
eliminated in the urine. For patients with
renal disease, do NOT exceed 20 g every
48 hours.
Precautions:
WARNING: Magnesium toxicity causes loss
of deep tendon reflexes, followed by
respiratory depression and ultimately
respiratory arrest. In most cases, therapy
can be monitored safely by hourly
measurement of the patellar reflex and
respiratory rate or oxygen saturation. If deep
tendon reflexes are absent, withhold further
doses until reflexes return. Toxicity can be
reversed with calcium gluconate.
Magnesium is excreted by the kidney.
Monitor regularly serum levels in women
with oliguria (urine output < 100 mL/4
hours.
Myasthenia gravis or other neuromuscular
diseases (use with extreme caution);
Renal impairment (use with caution);
Electrolyte abnormalities; Magnesium
toxicity; Pregnancy (monitor mother and
fetus closely; do not use for longer than
5–7 days to prevent adverse fetal events).
Adverse Drug Reactions:
Common: Flushing, nausea, vomiting
Less Common: Dizziness, drowsiness,
headache, thirst
Rare: Arrhythmias, cardiac arrest, coma,
confusion, loss of tendon reflexes, muscle
weakness, respiratory depression
Drug Interactions:
Monitor closely with:
Drugs that enhance the therapeutic effect of
Magnesium Sulfate – e.g.,
BLOOD AND BLOOD FORMING ORGANS
Aminoglycosides (additive neuromuscular
blocking effect)
Drugs whose therapeutic effects are enhanced
- Calcium Channel Blockers (hypotensive
effect) CNS Depressants, e.g.,
Barbiturates, Opiates, General Aesthetics
(CNS depressant effects) Neuromuscular
Blocking Agents, e.g., Tubocurarine,
Vecuronium, Succinylcholine
(neuromuscular blocking effect).
Drugs that increase risk of adverse or toxic
effects of Magnesium Sulfate: Calcium
Channel Blockers
The maximum rate of infusion is 1 g/hour in
asymptomatic patients. For doses < 6g,
infuse over 24 hours.
If the patient is severely symptomatic or has
conditions such as preeclampsia or
eclampsia, more aggressive therapy (≤4 g
over 4-5 minutes) may be required.
Pregnancy Category: A
ATC Code: B05XA05

Avoid concomitant use with:

Drugs that decrease absorption of Magnesium SODIUM CHLORIDE
Sulfate - Alpha-Lipoic Acid Rx
Drugs whose absorption may be decreased -
Alpha-Lipoic Acid, Multivitamins / Fluoride
Inj: 2.5 mEq/mL, 20 mL and 50 mL vial
with ADE (fluoride absorption) [separate
administration by at least 1 hour]
A sterile preparation that contains sodium
Drugs whose serum concentration may be
bicarbonate, utilized as an alkalizing
decreased - Bisphosphonate Derivatives
agent.
[except Pamidronate, Zoledronic Acid],
Deferiprone, Dolutegravir, Eltrombopag,
Indications:
Gabapentin, Levothyroxine, Multivitamins
Hyponatremia with overt manifestations.
/ Fluoride with ADE, Quinolone Antibiotics,
Raltegravir
Contraindications:
Gabapentin (CNS depressant effect) – Its
Where the administration of sodium or chloride
therapeutic effect may be enhanced.
could be clinically detrimental (e.g.,
Alfacalcidol, Calcitriol (systemic) - Increases
hypernatremia); fluid retention;
serum concentration of Magnesium
hypertension; CHF.
Sulfate:
Dose:
The dose is dependent on the degree of
Administration:
sodium depletion (i.e., moderately severe
Administer at a concentration not exceeding
hyponatremia where serum sodium is
20%. Dilute according to manufacturer’s
between 125–129 mmol/L or profound
instructions.
hyponatremia where serum sodium is
<125 mmol/L); on the severity of
For IM route, solutions may need dilution
symptoms (i.e., moderately or severely
before administration. 25% or 50% for
symptomatic); and on time of
adults or ≤20% for children.
development of hyponatremia (acute
For IV route, solutions must be diluted to ≤20% where hyponatremia is documented to
for IV infusion and may be administered exist <48hrs).
by IV push, IVPB, or continuous IV infusion.
IMPORTANT NOTE: Sodium deficit must be
For IV push, dilute first and do not administer corrected gradually in stages. Avoid
faster than 150 mg/minute. overtly rapid correction to prevent the

Page | 67
BLOOD AND BLOOD FORMING ORGANS
development of Osmotic Demyelination
Syndrome (previously named Central
Pontine Myelinolysis). The rate of
correction of hyponatremia should not be
more than 10 mmol/L (or 10 mEq/L) in
24 hours, or 18 mmol/L (or 10 mEq/L) in
48 hours.
Dose adjustments:
Renal impairment:
Select doses with caution due to the potential
to result in sodium retention and
increased risk of adverse effects.
Precaution:
WARNING: Contains aluminum, which may
be toxic. May reach toxic aluminum levels
with prolonged use, especially if kidney
function is impaired.
Monitor fluid balance, electrolyte
concentration, and acid-base balance;
observe for hypernatremia, water
retention, and pulmonary edema; restrict
in patients with renal insufficiency or
failure, cardiac failure, hypertension,
peripheral and pulmonary edema, or
toxemia of pregnancy; Seizures or
neurologic deficit (requires aggressive
therapy); IV administration can cause fluid
and/ or solute overloading resulting in
dilution of other electrolyte concentration,
overhydration, congested states or
pulmonary edema; excessive
administration of potassium-free
solutions may result in significant
hypokalemia; Premature neonates.
Adverse Drug Reactions:
Air embolization, febrile response, local
tenderness, tissue necrosis or infection at
the site of injection, venous thrombosis or
phlebitis extending from the site of
injection, extravasation
NOTE: May occur because of the solution,
added drugs, or the technique of
reconstitution or administration.
Page | 68
Drug Interactions:
Monitor closely with:
Corticosteroids e.g. Prednisone - Risk of
hypertension and edema of these drugs
may increase due to sodium and water
retention:
Administration:
Administer based on calculated dose
requirements for each patient. Must be
diluted before the infusion to avoid a
sudden increase in the plasma sodium
level. Too rapid administration should be
avoided [see Important Note under Dose].
Inspect visually for particulate matter and
discoloration before administration. Do
NOT use unless the solution is clear, and
the seal is intact. Discard unused
portions.
Pregnancy Category: C
ATC Code: B05XA03
STERILE WATER FOR
Rx INJECTION
Inj: 2 mL, 5 mL, 10 mL and 20 mL ampul
50 mL, 100 mL, 500 mL and 1 L
bottle/bag (no preservative)
A sterile, nonpyrogenic water for injection that
does not contain any antimicrobial agent
or other added substances, such as
buffer, and is supplied in single-dose
containers to dilute or dissolve drugs for
injection.
Indications:
For dissolving or diluting medicines that are
intended for parenteral injection.
NOTE: Use following the instructions set by the
manufacturer of the drug
Contraindications: No information found.
BLOOD AND BLOOD FORMING ORGANS
Do NOT store reconstituted solutions of drugs
Dose: for injection, unless otherwise directed.
Volume to be used for any drug for injection is
based on the vehicle concentration, dose, Do NOT reuse single-dose containers.
and route of administration as
recommended by the drug manufacturer. Do NOT heat over 66°C (150°F).

Precaution: Pregnancy Category: No information was found

WARNING: IV administration without a
solute may result in hemolysis. ATC Code: Not available.

Should be made isotonic before use; not for

direct infusion; not for non-automated
admixture preparations; Neonates and
very small infants.

NOTE: Upon reconstitution of medicines, label

to indicate that no antimicrobial or other
substance has been added and that it is
not suitable for IV injection without first
having been made approximately isotonic
by the addition of a suitable solute.

Adverse Drug Reactions: Febrile response,

local tenderness, abscess, tissue necrosis
or infection at the site of injection, venous
thrombosis or phlebitis extending from
the site of injection, extravasation.
NOTE: May occur because of the solution,
added drugs, or the technique
reconstitution or administration

Drug Interactions:
May be incompatible with some drugs for
injection in a given vehicle, or when
combined in the same vehicle.

Administration:
Inspect reconstituted drugs for clarity and
freedom from unexpected precipitation or
discoloration before administration.

Do NOT use for IV injection unless the osmolar

concentration results in an isotonic
admixture.

Do NOT use unless the solution is clear and

intact. mix thoroughly and use promptly
after diluting or dissolving drugs.
Page | 69
CARDIOVASCULAR SYSTEM
CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
CARDIAC GLYCOSIDES
DIGOXIN
Rx
Oral.: 250 micrograms tablet
A cardiac glycoside obtained from the leaves of
Digitalis lanata. Digoxin inhibits the Na+-
K+-ATPase pump and consequently
increases the force of cardiac contraction
and slows the heart rate.
Indications: For rate control in chronic atrial
fibrillation, atrial flutter, and cardiac
failure.
Contraindications: Ventricular tachycardia or
fibrillation; hypertrophic obstructive
cardiomyopathy (unless there is
concomitant atrial fibrillation and heart
failure); permanent or even intermittent
second-degree and third-degree
atrioventricular block without a cardiac
pacemaker; pre-excited atrial
fibrillation/atrial flutter or antidromic
atrioventricular reentrant tachycardia
associated with Wolff-Parkinson-White
(WPW) syndrome; arrhythmias caused by
cardiac glycoside intoxication
Dose:
Atrial fibrillation or flutter, by mouth, in ADULT,
• Rapid Oral Loading: 750–1,500
micrograms as a single dose; where
there is less urgency or greater risk of
toxicity, e.g., elderly, oral loading dose
is given in divided doses 6 hours apart,
Page | 70
with half of the total dose given as the
first dose; assess clinical response
before each additional dose;
• Slow Oral Loading: 250–750
micrograms daily for 1 week followed by
appropriate maintenance dose;
• Maintenance Oral Dose: 3.4–5.1
micrograms/kg daily or 125–500
micrograms daily; increase the dose
gradually every 2 weeks based on
clinical responses, toxicity, and serum
drug levels.
Heart failure, by mouth, ADULT, 125-250
micrograms (0.125-0.25 mg) once a
day as maintenance; higher doses
including 375 up to 500
micrograms/day are rarely needed.
Adjust maintenance dose by estimating
creatinine clearance and measuring
serum levels. Higher doses have no
additional benefit and may increase
toxicity.
Dose Adjustments:
Geriatric: Use lower doses due to the tendency
to develop the impaired renal function
and lean body mass which can lead to
digoxin toxicity.
Loading Dose: by mouth, 125–250
micrograms every 4–6 hours, to a
maximum of 500 micrograms;
Maintenance Dose: by mouth, 62.5–
125 micrograms once daily.
Renal impairment: For mild-to-moderate renal
impairment, reduce the dose. For
severe impairment, refer the patient to
a specialist.
For the following medical conditions:
Hypomagnesemia, hypokalemia,
hypercalcemia and hypothyroidism,
and hypoxia: Reduce dose
Precautions:
WARNING: Fatal arrhythmia may follow
overdose. Maintain heart rate above 60
beats/minute and early signs of toxicity
should be carefully monitored.
CARDIOVASCULAR SYSTEM
Acute myocarditis, such as rheumatic carditis;
advanced heart failure; severe pulmonary
disease; sick sinus syndrome; recent MI;
Fever and hyperthyroidism;
Hypomagnesemia, hypokalemia;
hypercalcemia, hypoxia; Hypothyroidism;
Renal impairment;
Elderly; Pregnancy (may need dose
adjustment); lactation (amount in
breastmilk too small to be harmful)
Adverse Drug Reactions:
Common: Abdominal pain, agitation, anorexia,
blurred vision, confusion, depression,
diarrhea, dizziness, drowsiness, nausea,
nightmares, visual disturbances,
vomiting.
Less Common: Acute psychosis, amnesia,
atrial or ventricular extrasystoles,
delirium, fatigue, gynecomastia,
hallucinations, headache, heart block,
intestinal ischemia, paroxysmal atrial
tachycardia, and fibrillation; shortened
QRS complex
Rare: Arrhythmias, rash, seizures,
thrombocytopenia, xanthopsia (yellow
vision)
Drug Interactions:
Monitor closely with:
Drugs that alter the absorption of Digoxin -
Acarbose (decreased absorption);
Macrolides, e.g., Azithromycin,
Clarithromycin, Erythromycin (increased
absorption).
Drugs that enhance the therapeutic effect of
Digoxin:
Amiodarone (slowing cardiac conduction),
Beta Blockers, e.g., Atenolol, Propranolol
(slow atrioventricular conduction), Diltiazem
(additive negative effects on heart rate and
cardiac conduction)
Avoid concomitant use with:
Drugs that decrease the serum concentration
of Digoxin - Antacids, e.g., Aluminum or
Magnesium Hydroxide, Rifampicin,
Salbutamol
Drugs that reduce the therapeutic effect of
Digoxin by reducing its absorption - Bile Acid
Binding Resins Increases serum
concentration of Digoxin, increasing its risk
of adverse or toxic effects: Verapamil
(additive negative effects on heart rate and
cardiac conduction)
Administration:
To be taken 1 hour before or 2 hours after
eating food. For meals high in fiber, take
digoxin 2 hours before or 2 hours after
eating food.
IM route is generally not preferred due to
severe injection site pain.
Pregnancy Category: C
ATC Code: C01CA05
CARDIAC STIMULANTS, EXCLUDING
CARDIAC GLYCOSIDES
DOPAMINE
Rx (AS HYDROCHLORIDE)
LERGY AND IMMUNE SYST
Inj.: 40 mg/mL, 5 mL vial/ampul (IV)
80 mg/mL, 5 mL vial (IV)
800 micrograms/mL, 250 mL D5W (pre‐
mixed) (IV)
A direct-acting sympathomimetic, which acts
on beta1 receptors in cardiac muscles,
leading to increased contractility with
little effect on the rate. Dopamine may
be given for short periods in the
treatment of severe heart failure; it also
causes renal vasodilation, thus
preserving renal perfusion and renal
function. It also has peripheral
vasoconstricting properties when given
at higher doses.
Indications: Hypovolemic shock and
hemorrhagic shock as adjuvant therapy
to volume replacement; cardiogenic
Page | 71
CARDIOVASCULAR SYSTEM
shock (where systolic BP <90 in adults);
septic shock.
Contraindications: Ischemic heart disease;
tachyarrhythmias, ventricular
fibrillation; pheochromocytoma;
hyperthyroidism
Dose:
Hypovolemic and hemorrhagic shock as
adjuvant
therapy to volume replacement, by IV
infusion into a large vein, ADULT,
initially 5 micrograms/kg per minute,
gradually increase by 5–10
micrograms/kg per minute according to
blood pressure, cardiac output, and
urine output (seriously-ill patients, up to
20 micrograms/kg per minute); CHILD,
2–10 micrograms/kg per minute
depending on patient response.
Dose Adjustments:
Renal and Hepatic Impairment: For mild-to-
moderate impairment, dose reduction
may be warranted. Use with caution
For severe impairment, refer the patient to a
specialist.
Precautions:
WARNING: This may cause peripheral
ischemia in patients with a history of
occlusive vascular disease (e.g.,
atherosclerosis and Raynaud’s syndrome).
In case of extravasation causing peripheral
ischemia, use phentolamine for local
infiltration
NOTE: Dosage is critical – at low doses, it
stimulates myocardial contractility and
increases cardiac output; however, higher
doses (more than 5 micrograms/kg per
minute) cause vasoconstriction, which
increases blood pressure and may also
cause worsening of heart failure.
Close monitoring of arterial and venous
pressure and continuous ECG should be
performed; treatment with
sympathomimetics should be guided by
Page | 72
hemodynamic monitoring (individualize
treatment depending on the clinical
response); use low dose in cardiogenic
shock due to MI; prolonged use of
sympathomimetics may result in the
diminution of therapeutic effect
(downregulation of receptors;
disproportionate increase in diastolic
pressure).
Correct hypovolemia before treatment and
maintain blood volume during treatment;
correct hypoxia, hypercapnia, and
metabolic acidosis before or at the start of
treatment (may reduce effectiveness
and/or increased incidence of adverse
effects of dopamine)
Pulmonary hypertension (may be worsened
due to dopamine-induced pulmonary
vasoconstriction); suppresses the
pituitary secretion of thyroid-stimulating
hormone, growth hormone, and prolactin
Elderly;
Pregnancy (limited human data available)
Adverse Drug Reactions:
Common: Anginal pain, chest pain, dyspnea,
ectopic beats, flushing, headache,
hypotension with dizziness, nausea,
palpitations, peripheral vasoconstriction,
vomiting, tachycardia.
Less Common: Abnormal ventricular
conduction, bradycardia, extravasation
(may cause necrosis and sloughing of
surrounding tissue), fainting, gangrene,
hypertension, mydriasis, piloerection,
uremia
Rare: Allergic reactions, ventricular arrhythmia.
Drug Interactions:
Monitor closely with:
Drugs that enhance the therapeutic effect of
Dopamine - MAO Inhibitors, e.g., Linezolid,
Phenelzine, Tranylcypromine
Drugs that increase risk of adverse or toxic
effects of Dopamine - Phenytoin
(hypotension; bradycardia)
CARDIOVASCULAR SYSTEM
Drugs that reduce the therapeutic effect of
Dopamine - Alpha-adrenergic Blocking
Agents.
Avoid concomitant use with:
Metoclopramide (inhibits GI absorption) -
Decrease serum concentration of
dopamine
Vasoconstrictors, e.g., Ergot Alkaloids
(peripheral ischemia) - Increases risk of
adverse or toxic effects of dopamine
Drugs that reduce the therapeutic effect of
dopamine-
Beta-adrenergic Blocking Agents, e.g.,
Propranolol, Metoprolol (with cardiac
effects); Chlorpromazine (with
hypertensive effects); Fluphenazine (with
hypertensive effects); Haloperidol (with
hypertensive effects); Vasoconstrictors,
e.g., Ergot Alkaloids (with peripheral
vasoconstriction).
Administration: Administer via a large vein high
up in the limb, preferably the arm, to avoid
tissue necrosis.
Dilute solution, usually to 1.6 or 3.2 mg/mL, in
dextrose 5% or sodium chloride 0.9%
before administration. Premixed
dopamine solution is also available in
single/double concentration.
Do NOT admix with alkaline solutions, such as
sodium bicarbonate to prevent drug
inactivation.
Pregnancy Category: C; D in 3rd trimester
ATC Code: C01CA04
EPINEPHRINE
Rx
(ADRENALINE)
Inj.: 1 mg/mL, 1 mL ampul (IM, SC) (as
hydrochloride)
A direct-acting, mixed alpha- and beta-
adrenoceptor agonist; a
sympathomimetic catecholamine, which
is a potent cardiac stimulant, peripheral
vasoconstrictor, and bronchodilator.
NOTE: Vasodilator at a low dose (beta2-
receptors). Vasoconstrictor at high dose
(alpha-receptors).
Indications: Management of anaphylactic
shock; may be used in cases of serious
and fatal anaphylaxis; cardiac arrest.
Contraindications: Known hypersensitivity to
epinephrine or any of the excipients;
pheochromocytoma; use in local
anesthesia of fingers, toes, ears, nose, or
genitalia; shock; organic heart disease or
cardiac dilatation; closed-angle
glaucoma; labor
NOTE: There are no absolute contraindications
to the use of epinephrine in life-
threatening allergic reactions.
Dose:
Anaphylaxis, by IM or SC injection of 1:1,000
injection, ADULT and ADOLESCENT,
500 micrograms (0.5 mL); CHILD 6–12
years old, 250 micrograms (0.25 mL);
CHILD 6 months to 6 years old, 120
micrograms (0.12 mL); INFANT <6
months old, 50 mcg (0.05 mL); repeat
if necessary at intervals of 20 minutes
to 4 hours depending on the response
of the patient and the severity of the
condition (maximum single dose, 500
micrograms).
Anaphylaxis, by slow IV injection of 1:10,000
(given at a rate of 1 mL/minute)
epinephrine injection; this route should
be reserved for severely ill patients
when there is doubt about the
adequacy of circulation and absorption
from the IM site, ADULT, 500
micrograms (5 mL); CHILD, 10
micrograms/kg (0.1 mL/kg), given over
several minutes.
Page | 73
CARDIOVASCULAR SYSTEM
Cardiac arrest (asystole), by IV injection, hypertension, peripheral ischemia and
ADULT, the recommended dose is 1 mg necrosis (at infusion site), pulmonary
IV, using 10 mL of the 1:10,000 edema, ventricular arrhythmias
solution. This may be repeated every 3- Rare: Allergic reactions
5 minutes. If given through a peripheral
line, each dose should be followed by a Drug Interactions:
flush of 20 mL of IV fluid to ensure NOTE: Alpha-adrenergic blockers antagonize
delivery of the drug to the central vasoconstricting and hypertensive effects
compartment. Intracardiac of epinephrine.
administration is no longer
recommended; CHILDREN, the Monitor closely with:
recommended dose is 10 micrograms Tricyclic Antidepressants (blocks
(0.1 mL of the 1:10,000 solution)/kg catecholamine uptake) – Increases the
body weight administered IV. This may therapeutic effect of epinephrine
be repeated every 3-5 minutes. Drugs causing Potassium loss, [e.g.,
Corticosteroids, Potassium-depleting
Dose Adjustments: Diuretics, Aminophylline, Theophylline
No information found (hypokalemia)], Oxytocin
(hypertension), Tricyclic
Precautions: Antidepressants (arrhythmia) -
Cerebrovascular disease (increased risk of Increase the risk of adverse or toxic
peripheral ischemia or stroke); effects of Epinephrine
hypovolemia (correct before using Ergot Alkaloids (pressor effect) – Reverses the
epinephrine); acidosis, hypercapnia, or therapeutic effect of epinephrine.
hypoxia (may reduce effectiveness and
increase the incidence of adverse Avoid concomitant use with:
effects); heart diseases, e.g., ischemic Beta-Blockers (hypertension followed by
heart disease, heart failure, other bradycardia) – Increase the risk of
arrhythmias (increased risk of adverse effects of epinephrine
arrhythmias, angina, and myocardial Alpha-Blockers (vasoconstricting and
ischemia); aortic stenosis and hypertensive effects), Beta Blockers
hypertrophic cardiomyopathy (may (prevents receptor activation) - Reduce
increase outflow obstruction); the therapeutic effect of Epinephrine:
arrhythmias; pulmonary hypertension Hypoglycemic Agents– the therapeutic effect
(may worsen due to pulmonary may be decreased by epinephrine (loss
vasoconstriction). of blood sugar control)
Hyperthyroidism or diabetes mellitus (adverse
reactions are more likely to occur) Administration:
Elderly; Best administered by SC or IM injection into the
Pregnancy (use with caution during the second anterolateral aspect of the middle third
stage of labor). of the thigh for anaphylaxis.
Or by IV injection for cardiac arrest or
Adverse Drug Reactions: emergencies.
Common: Anxiety, dizziness, dyspnea, fear, Administer by slow IV injection only in severely
headache, hyperglycemia, nausea, pallor, ill patients when there is doubt about
palpitations, restlessness, sweating, the adequacy of circulation and
tachycardia, tremor, vomiting, weakness absorption from the IM site.
Less Common: Angina, cerebral hemorrhage,
excessive increase in blood pressure, Do NOT administer by intracardiac injection.
Page | 74
CARDIOVASCULAR SYSTEM
Do NOT mix with alkaline solutions. Discard
after 24 hours or if the solution is
discolored or contain precipitates.
NOTE: If a central line is used, an infusion
pump is required.
If given through a peripheral line, each dose
should be followed by a flush of 20 mL
of IV fluid to ensure delivery of the drug
to the central compartment
Pregnancy Category: C
ATC Code: C01CA24
VASODILATORS USED IN CARDIAC
DISEASES
ISOSORBIDE DINITRATE
Rx
Oral: 10 mg and 20 mg tablet
20 mg MR tablet/capsule
Sublingual: 5 mg tablet
An organic nitrate vasodilator with better
stability in storage than nitroglycerin. It is
useful in patients who require nitrates
infrequently because of its slower onset of
action but longer duration. Commonly
used as a PRN drug.
Indications: Prophylaxis and treatment of
angina
Contraindications: Hypersensitivity to
isosorbide and any of its components;
hypotension; hypovolemia; hypertrophic
obstructive cardiomyopathy; aortic
stenosis; cardiac tamponade; constrictive
pericarditis; mitral stenosis; marked
anemia; head trauma; cerebral
hemorrhage; angle-closure glaucoma; GI
hypermotility; malabsorption syndrome
Dose:
Angina, acute attack, by sublingual route,
ADULT, 2.5–5 mg, repeated every 5–10
minutes as required for 3 doses
IMPORTANT NOTE: Inability to relieve
chest pain after 3 doses may signal
acute MI, which will need immediate
hospitalization. IV infusion may be
started while awaiting transfer to the
hospital, at 1 mg/hour and titrated
upward to 4 mg/hour.]
Angina prophylaxis, by mouth, ADULT,
• As regular release tablet, initially 5–
20 mg 2–3 times daily
(maintenance dose, 10–40 mg 2–
3 times daily; maximum dose, 240
mg);
• As MR tablet, 40–80 mg 1–2 times
daily, space twice-daily dose 6
hours apart (maximum dose, 160
mg daily).
NOTE: Provide nitrate-free intervals
daily (14 hours for regular release and
18 hours for extended-release) to avoid
the development of tolerance.
Acute angina, prevention before a precipitating
activity, by sublingual route, ADULT, 5–
10 mg taken 10 minutes before
activity.
Chronic angina, prevention, by mouth, ADULT,
5-20mg (maintenance 10–40 mg) up
to 3 times daily.
Dose Adjustments:
Renal Impairment: Consider dose reduction.
Significant accumulation of the active
metabolites may occur with chronic
use.
Hepatic impairment: Consider dose reduction.
Partially metabolized by the liver.
Precautions:
Page | 75
CARDIOVASCULAR SYSTEM
Long-term therapy (may develop nitrate
tolerance; administer nitrate-free interval
daily to prevent tolerance).
Severe hepatic impairment; renal impairment;
hypothyroidism; recent history of MI;
malnutrition; hypothermia.
Pregnancy (may cross the placenta; avoid
medication unless the potential benefit
outweighs risk).
Adverse Drug Reactions:
Common: Dizziness, fainting, flushing,
hypotension (including orthostatic
hypotension), palpitations, peripheral
edema, tachycardia, throbbing headache
Less common: Heartburn, hypoxemia, nausea,
rash, rebound angina, syncope, vomiting
Rare: Angle-closure glaucoma
Drug Interactions:
Monitor closely with:
Drugs that reduce blood pressure - Enhance
the therapeutic effect of ISDN
(hypotensive effects)
Atropine - reduces the therapeutic effect of
ISDN (failure to dissolve under the
tongue owing to dry mouth)
Avoid concomitant use with:
Phosphodiesterase Inhibitors [e.g., Sildenafil -
Increase risk of adverse or toxic effects of
ISDN (hypotension; MI)]
Dexamethasone, Hydrocortisone Ibuprofen,
Oral Contraceptives, Prednisolone due to
the antagonism of hypotensive effect -
Reduce the therapeutic effect of ISDN
Administration:
For oral administration, take on an empty
stomach ½ hour before meals.
For sublingual tablets, sit or lie down before
use since the tablet may cause dizziness.
Place the appropriate dose under the
tongue. Do NOT swallow. After the pain
has been relieved, the patient may spit
out or swallow what is left of the tablet to
avoid adverse effects, such as
headaches.
Page | 76
Pregnancy Category: C
ATC Code: C01DA08
ISOSORBIDE-5-
Rx MONONITRATE
Oral: 30 mg and 60 mg MR tablet/capsule
An antianginal agent that forms free radical
nitric oxide. Nitric oxide activates
guanylate cyclase in the smooth muscle
which leads to smooth muscle relaxation
and a prominent vasodilator effect on the
peripheral veins. It also reduces cardiac
oxygen demand by decreasing preload
and afterload due to its vasodilatory
effect. It likewise causes epicardial
coronary arteries vasodilation
Indications: Prevention of angina pectoris.
Contraindications: Hypersensitivity to organic
nitrates; concurrent use with phospho-
diesterase5 inhibitors
Dose:
Angina, by mouth, ADULT,
• As regular release tablet, initially 5–20
mg twice daily, given 7 hours apart to
decrease tolerance development;
patients initiating therapy with 5 mg
twice daily should be titrated up to 10
mg twice daily in the first 2–3 days;
• As MR tablet, initially 30–60 mg once
daily in the morning; titrate upward
as needed with at least 3 days
between increases (maximum single
daily dose, 240 mg).
Dose Adjustments:
Geriatric:
Start with the lowest recommended adult
dose. Administer the first dose in a
physician's office to observe for maximal
cardiovascular dynamic effects and
adverse effects. Adjust dose or change
CARDIOVASCULAR SYSTEM
medication when reflux esophagitis
occurs.
Precautions:
Long-term therapy (may develop tolerance;
administer nitrate-free interval daily to
prevent tolerance)
Hypotension or bradycardia (may be
accompanied by paradoxical bradycardia
and increased angina pectoris; increased
risk of hypotension; orthostatic
hypotension)
Hypertrophic cardiomyopathy (may reduce
preload, exacerbate obstruction, and
cause hypotension or syncope and/or
worsening of heart failure)
Increased intracranial pressure (may worsen
clinical outcomes in patients with
neurologic injury)
Lactation (not known if excreted in breastmilk)
Adverse Drug Reactions:
Common: Angina, flushing, headache,
dizziness, fatigue, pain, emotional lability,
pruritus, rash, nausea, abdominal pain,
diarrhea, upper respiratory infection,
cough, allergic reaction
Less Common: Amblyopia, anorexia, anxiety,
apoplexy, arrhythmia, asthma, back pain,
bradycardia, impaired concentration,
depression, diaphoresis, dyspepsia,
dyspnea, edema, hypertension or
hypotension, insomnia, MI, muscle
cramps, neck pain, nervousness,
nightmares, orthostatic hypotension,
pallor, palpitation, paresthesia, prostatic
disorder, restlessness, sinusitis, susurrus
aurium, tachycardia, taste disturbance,
thirst, tremor, vertigo, vomiting,
xerostomia
Rare: Methemoglobinemia
Drug Interactions:
Monitor closely with:
Drugs that enhance the therapeutic effect of
ISMN:
Antihypertensive effect: Barbiturates e.g.,
Phenobarbital, Molsidomine, Nicorandil;
Vasodilatory effect: Ethyl alcohol
Drugs that increase the risk of adverse or toxic
effects of ISMN:
Other Antihypertensive Agents
ISMN may also increase the risk of adverse or
toxic effects of the following drugs:
Risk of Methemoglobinemia - Dapsone,
(Topical), Nitric Oxide, Prilocaine, Sodium
Nitrite;
Risk of Orthostatic hypotension -
Duloxetine, Levodopa, Risperidone
(hypotensive effect), Rosiglitazone
(ischemia).
Avoid concomitant use of medicines that:
Drugs that decrease the serum concentration
of ISMN - CYP3A4 Inducers
Drugs that enhance the therapeutic effect of
ISMN -
Phosphodiesterase-5 Inhibitors e.g.
Sildenafil (vasodilatory effects)
Drugs that increase the serum concentration
of ISMN - CYP3A4 Inhibitors, Fusidic Acid
(Systemic),
Administration:
Do NOT administer around-the-clock.
For immediate release tablets, schedule twice-
daily doses 7 hours apart (8 AM and 3
PM).
For MR tablets, administered once daily in the
morning upon rising with a half-glassful of
fluid.
Do NOT chew or crush MR tablets. MR tablets
that are scored may be split.
Pregnancy Category: B / C (product-specific)
ATC Code: C01DA14
Page | 77
CARDIOVASCULAR SYSTEM
AGENTS ACTING ON
ARTERIOLAR SMOOTH MUSCLE
ANTIHYPERTENSIVES
HYDRALAZINE
Rx
Inj.: 20 mg/mL (as hydrochloride), 1 mL
ampule (IM, IV)
A direct vasodilator of arterioles with little
effect on veins and decreased systemic
resistance.
Indication:
Management of hypertensive emergencies in
pregnant women at the birthing facilities.
Contraindications: Mitral valve rheumatic
heart disease
Dose:
Hypertensive emergency in pregnancy with
systolic BP ≥160 mmHg or diastolic BP
≥110 mmHg, by IM or IV injection, ADULT,
initially 5 or 10 mg, may repeat the dose in
20–40 minutes with 5–10 mg if blood
pressure continues to exceed thresholds
(maximum total cumulative dose, 20 mg IV
or 30 mg IM); after the initial dose, may
initiate a continuous infusion of 0.5–10
mg/hour instead of intermittent dosing.
Dose Adjustment:
Renal Impairment: For patients with CrCl of
10–50 mL/minute, administer every 8 hours.
For patients with CrCl <10 mL/minute,
administer every 8–16 hours in fast
acetylators and every 12–24 hours in slow
acetylators.
Page | 78
Precautions:
Drug-induced lupus-like syndrome (dose-
related); fluid or sodium retention (drug-
induced; may require the addition or
increased dose of a diuretic); peripheral
neuritis (associated with paresthesia,
numbness, and tingling, possibly due to an
anti-pyridoxine effect).
Cardiovascular disease (increase in
tachycardia may increase myocardial
oxygen demand); pulmonary hypertension
(may cause hypotension); renal
impairment; hepatic impairment
(undergoes extensive hepatic metabolism).
Elderly.
Pregnancy (crosses the placenta; may cause
adverse events); lactation (excreted into
breastmilk; use with caution in nursing
mothers).
Adverse Drug Reactions:
Common: Angina pectoris, flushing, orthostatic
hypotension, palpitations, paradoxical
hypertension, peripheral edema,
tachycardia, vascular collapse, anxiety,
chills, depression, disorientation, dizziness,
fever, headache, increased intracranial
pressure, psychotic reaction, pruritus, rash,
urticaria, anorexia, constipation, diarrhea,
nausea, paralytic ileus, vomiting, dysuria,
impotence, agranulocytosis, eosinophilia,
erythrocyte count reduced, hemoglobin
decreased, hemolytic anemia, leukopenia,
muscle cramps, peripheral neuritis,
rheumatoid arthritis, tremor, weakness,
conjunctivitis, lacrimation, dyspnea, nasal
congestion
Less Common: Diaphoresis, drug-induced
lupus-like syndrome, fever, arthralgia,
splenomegaly, lymphadenopathy, asthenia,
myalgia, malaise, pleuritic chest pain,
edema, positive ANA and LE cells,
maculopapular facial rash, positive direct
Coombs' test, pericarditis, pericardial
tamponade
Rare: Thrombocytopenia
CARDIOVASCULAR SYSTEM
Drug Interactions:
Monitor closely with: AGENTS ACTING ON THE
Drugs that enhance the antihypertensive effect RENIN-ANGIOTENSIN SYSTEM
of Hydralazine-
Alfuzosin, Barbiturates, Brimonidine
(Topical), Diazoxide, Herbs with hypotensive ACE INHIBITORS, PLAIN
properties, Other Antihypertensive Agents,
Nicorandil, Pentoxifylline, GENERAL INFORMATION
Phosphodiesterase-5 Inhibitors,
Prostacyclin Analogues Mode of Action: This drug class acts by
Drugs that increase the risk of adverse or toxic inhibiting the Angiotensin-Converting
effects of Hydralazine: Enzyme (ACE), which produces two
Orthostatic hypotension: Duloxetine, Other mechanisms to reduce blood pressure.
Antihypertensive Agents, Levodopa, MAO First, by inhibiting the conversion of
Inhibitors [except Linezolid, Tedizolid] Angiotensin I to Angiotensin II, a potent
Drugs that reduce the antihypertensive effect
vasoconstrictor that stimulates the
of Hydralazine:
release of norepinephrine. Its other
Methylphenidate, Nonsteroidal Anti-
mechanism is the prevention of the
inflammatory Agents e.g., Ibuprofen
breakdown of bradykinin, a vasodilator
Risperidone – with increased risk of adverse or
toxic effects (hypotensive effect) substance.

Avoid concomitant use with: Precautions:

Rituximab – Hydralazine Increases risk of
adverse or toxic effects (hypotensive
effects) of these drugs
TEST INTERACTION. Produces a positive direct
Coombs’ Test, interfering with blood cross-
matching.
Administration: Food enhances bioavailability
when taken orally. Administer consistently
with meals.
For IV route, administer as a slow IV push
with a maximum rate of 5 mg/minute.
Pregnancy Category: C
ATC Code: C02DB02
WARNING: Overzealous treatment with ACE
inhibitors may lead to sudden hypotension,
renal insufficiency or failure, or
hyperkalemia with the risk of arrhythmia.
Drugs acting directly on the renin-
angiotensin system can cause injury and
death to a developing fetus. When
pregnancy is detected, discontinue as soon
as possible.
NOTE: ACE inhibitors should be initiated with
careful clinical monitoring in those:
• With severe heart failure;
• Receiving multiple or high-dose diuretic
therapy;
• With hypovolemia;
• With hyponatremia (plasma-sodium
concentration <130 mmol/L);
• With hypotension (SBP<90 mmHg);
• With unstable heart failure;
• Receiving high dose vasodilator therapy;
• Known vascular disease.

Cough (dry, hacking, non-productive, which

usually occurs within the first few months
of treatment and should generally resolve

Page | 79
CARDIOVASCULAR SYSTEM
within 1-4 weeks after discontinuation of
the ACE inhibitor).
Angioedema (may occur rarely; may involve
head and neck, or the intestine);
Peripheral vascular disease
generalized atherosclerosis (risk of
renovascular disease)
Collagen vascular disease (increased risk of
agranulocytosis)
Severe or symptomatic aortic stenosis (risk of
hypotension); Hypertrophic
cardiomyopathy Renal impairment
(increased risk hyperkalemia; may affect
the excretion of ACE inhibitors);
Hepatic impairment; jaundice or marked
elevations of hepatic enzymes
(discontinue use due to risk of hepatic
necrosis);
Renal artery stenosis
Neutropenia and agranulocytosis
Obstructive sleep apnea
Surgery (excessive hypotension may occur
during anesthesia and after surgery)
Hypotension with the first dose, especially in
patients on diuretics, on a low-sodium
diet, on dialysis, dehydrated, or with heart
failure.
Concomitant use of statins (increased risk of
myopathy; limit simvastatin dose to 20
mg daily if used concurrently).
Elderly (may be more predisposed to first-dose
hypotension, hyperkalemia, and
renovascular disease)
Pregnancy (use in the first trimester may cause
major congenital malformations; use in
the second and third trimester may cause
fetal renal dysfunction and
oligohydramnios, and subsequently fetal
death); lactation (avoid use in the first few
weeks after delivery, particularly in
preterm infants; risk of profound neonatal
hypertension).
NOTE: Initiation of therapy in patients with
ischemic heart disease or
cerebrovascular disease warrants close
observation due to the potential
consequences posed by falling blood
pressure, e.g., MI, stroke. Fluid
Page | 80
replacement may restore blood pressure
if needed. Discontinue therapy if
hypotension recurs.
or Concomitant use of ARB or renin inhibitor, e.g.,
Aliskiren, is associated with an increased
risk of hypotension, hyperkalemia, and
renal dysfunction.
USE WITH DIURETICS. Initiate at very low doses
to minimize the risk of very rapid fall in
blood pressure in volume-depleted
patients. Discontinue or significantly
reduce high-dose diuretic therapy, e.g.,
with furosemide at doses >80 mg daily, at
least 24 hours before starting enalapril
(may not be possible in heart failure due
to the risk of pulmonary edema). If high-
dose diuretic therapy cannot be stopped,
medical supervision is advised for at least
2 hours after administration or until blood
pressure is stable.
CAPTOPRIL
Rx
Oral: 25 mg tablet
An ACE inhibitor that is useful in treating
hypertension, decreasing morbidity and
mortality in heart failure and left
ventricular dysfunction after myocardial
infarction, and delaying the progress of
diabetic nephropathy.
Indications: Management of mild-to-moderate
essential hypertension (alone, or with
thiazide-diuretic therapy) and severe
hypertension resistant to other treatment.
Contraindications: Significant hyperkalemia;
hypotension; significant bilateral renal
artery stenosis; angioedema; pregnancy;
concurrent use with Aliskiren in patients
with DM or renal impairment
CARDIOVASCULAR SYSTEM
Dose: disturbances, Stevens-Johnson
NOTE Titrate dose according to patient's syndrome, syncope, toxic epidermal
response. Use the lowest effective dose. necrolysis, visceral angioedema

Hypertension, by mouth, ADULT, initially 25 mg Drug Interactions:

twice daily, may increase by 12.5–25 mg
per dose at 1- to 2-week intervals up to a
total dose of 150 to 200 mg daily in 2
divided doses.
Hypertensive urgencies, by mouth, ADULT, 25
mg, may repeat as required.
Dose Adjustments:
Geriatric:
Start treatment with lower doses.
Renal impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted. For severe
impairment, refer the patient to a
specialist.
Monitor closely with medicines that:
Enhance the antihypertensive effect of
Captopril -
Other antihypertensive agents e.g.
diuretics, other drugs which reduce blood
pressure
Increase risk of adverse or toxic effects of
Captopril -
Angiotensin II Receptor Blockers e.g.,
Losartan, Loop Diuretics e.g., Furosemide
(severe hypotension with the first ACE
inhibitor dose), Drugs which reduce blood
pressure (ACE inhibitor-induced renal
impairment), Thiazide Diuretics (severe
hypotension with the first ACE inhibitor
dose)

Adverse Drug Reactions: Avoid concomitant use with:

Common: Cough, dizziness, dysgeusia, fatigue, Drugs that decrease the serum concentration
headache, hyperkalemia, hypersensitivity of Captopril:
reactions, hypertension, malaise, nausea, Antacids, e.g., Aluminum or Magnesium
rash Hydroxide
Less Common: Abnormal dreams, Drugs that increase the risk of adverse or toxic
anaphylactoid reactions, angina pectoris, effects (hyperkalemia) of Captopril:
anorexia, chest pain, congestive heart Selective and Non-selective NSAIDs, (also
failure, constipation, diarrhea, dry mouth, renal impairment); Potassium
elevated hepatic aminotransferases, Supplements; Drugs that cause
alkaline phosphatase, and serum Potassium retention, e.g., Potassium-
bilirubin; fever, flushing, hoarseness, sparing Diuretics
itching, muscle cramps, MI, pallor, Drugs that reduce the therapeutic effect of
palpitations, Raynaud’s syndrome, sore Captopril:
throat, stomatitis, tachycardia, taste Indomethacin, Selective and Non-
disturbances, urticaria, vomiting Selective NSAIDs, Salicylates (other
Rare: Acute renal failure, bronchospasm, beneficial pharmacodynamic effects
cardiac arrest, cerebrovascular desired for the treatment of CHF)
insufficiency, dyspnea, angioedema,
erythema multiforme, exfoliative Administration:
dermatitis, gynecomastia, hepatitis, Take on an empty stomach. The patient may
hemolytic anemia, hyponatremia, feel dizzy when taking this medicine.
impotence, neuropathy, myalgia, oliguria, Advise the patient to get up gradually from
orthostatic hypotension, pancreatitis, a sitting or lying position to minimize this
pancytopenia, polyuria, proteinuria, effect, and to sit or lie down if the patient
psoriasis, renal insufficiency, serum becomes dizzy or light-headed.
sickness-like syndrome, rhythm
Page | 81
CARDIOVASCULAR SYSTEM
See General Information on Agents Acting on Hepatic impairment: For mild-to-moderate
the Renin-Angiotensin System – ACE impairment, no dose adjustment is
Inhibitors, Plain in Chapter 3: needed. For severe impairment, refer
Cardiovascular System for information on the patient to a specialist
Warnings and Precautions.
Renal impairment:
Pregnancy Category C in 1st trimester, For mild-to-moderate impairment, dose
D in 2nd & 3rd trimesters reduction is warranted. For severe
impairment, refer the patient to a
ATC Code: C09AA01 specialist.

Adverse Drug Reactions:

Common: Blurred vision, cough, depression,
ENALAPRIL
Rx dizziness, dyspnea, headache,
hyperkalemia, hypertension
Less Common: Abnormal dreams, alopecia,
Oral: 5 mg and 20 mg tablet anaphylactoid reactions, angioedema,
anorexia, chest pain, confusion,
An oral ACE inhibitor is converted by hydrolysis diarrhea, drowsiness, dry cough,
in the body to enalaprilat. Its effects are elevated hepatic aminotransferases,
similar to captopril. and bilirubin; dry mouth, fatigue, fever,
flushing, hoarseness, hypotension,
Indications: Management of hypertension; impotence, insomnia, muscle cramps,
heart failure. nausea, nervousness, palpitations,
rash, renal impairment, sweating,
Contraindications: Significant bilateral renal tinnitus, urticaria, vertigo
artery stenosis; renovascular disease; Rare: Abdominal pain, agranulocytosis, allergic
pregnancy; significant hyperkalemia; alveolitis, aplastic anemia,
hypotension; history of angioedema (ACEI arrhythmias, electrolyte disturbances,
induced, hereditary or idiopathic); exfoliative dermatitis, bronchospasm,
concurrent use of aliskiren in patients GI angioedema, gynecomastia,
with DM or renal impairment hepatitis, hemolytic anemia,
hypersensitivity-like reactions,
Dose: hyponatremia, ileus, liver damage,
Heart failure, adjunct or asymptomatic left neuropathy, neutropenia, paresthesia,
ventricular dysfunction, by mouth, ADULT, peptic ulcer, pancreatitis, proteinuria,
initially 2.5 mg once daily, increased pulmonary infiltrates, psoriasis,
gradually over 2–4 weeks to 10–20 mg Raynaud’s syndrome, Stevens-Johnson
twice daily if tolerated. syndrome, thrombocytopenia, toxic
Hypertension, by mouth, ADULT, initially 5 mg epidermal necrolysis, visceral
once daily (lower dose if used in addition angioedema, vomiting.
to a diuretic); increased at intervals of 1–
2 weeks up to a total dose of 20 mg daily Drug Interactions:
in 1 or 2 divided doses; CHILD, refer to a Monitor closely with:
specialist. Drugs that enhance the therapeutic effect of
Enalapril - Drugs that reduce blood
Dose Adjustments: pressure
Drugs that increase the risk of adverse or toxic
effects of Enalapril -
Page | 82
CARDIOVASCULAR SYSTEM
Digoxin (cardiac toxicity), Loop Diuretics
(profound diuresis; serious electrolyte
disturbance), Potassium lowering Drugs
(hypokalemia), Salbutamol (hypokalemia)
Avoid concomitant use with:
Ibuprofen (nephrotoxicity) Selective and Non-
selective NSAIDs (nephrotoxicity) -
Enalapril may increase the risk of adverse
or toxic effects of these drugs
Lidocaine, Metformin (antagonism of
hypoglycemic effect), Selective and non-
selective NSAIDs (renal function, diuretic
and hypotensive effect) - Enalapril may
reduce the therapeutic effect of the
following drugs
Administration:
Take once daily in the morning. If to be taken
twice daily, take the first dose in the
morning and the second dose before 6 in
the evening.
See General Information under Agents Acting
on the Renin-Angiotensin System – ACE
Inhibitors, Plain in Chapter 3:
Cardiovascular System for information on
Warnings and Precautions.
Pregnancy Category: B
ATC Code: C09AA02
ENALAPRIL +
Rx HYDROCHLOROTHIAZIDE
Oral: 20 mg enalapril + 12.5 mg
hydrochlorothiazide tablet
Enalapril blocks the renin-angiotensin-
aldosterone axis and reverses the
potassium loss associated with the
diuretic
Hydrochlorothiazide increases plasma renin
activity, increases aldosterone secretion,
and decreases serum potassium.
Indications: Treatment of hypertension
Contraindications: Hypersensitivity to other
sulfonamide derived drugs; history of
angioedema; idiopathic angioedema;
anuria; diabetes; co-administration with a
neprilysin inhibitor
Dose:
Hypertension, by mouth, ADULT, 10–25 mg
enalapril with 12.5–50 mg
hydrochlorothiazide daily as a single dose
or in 2 divided doses.
Dose Adjustments:
Renal impairment:
In patients with severe impairment, use is not
recommended. Loop diuretics are
preferred to thiazide diuretics.
Precautions:
WARNING: Fetal Toxicity. Drugs acting
directly on the renin-angiotensin system can
cause injury and death to the developing
fetus. When pregnancy is detected,
discontinue as soon as possible.
Hypotension (excessive hypotension and
syncope has been reported; in patients
with CHF with or without associated
renal insufficiency, excessive
hypotension may be associated with
oliguria and/or progressive azotemia).
Anaphylactoid and related reactions
(exacerbation or activation of systemic
lupus erythematosus has been
reported; may be subject to a variety of
adverse reactions, some serious; have
been reported in patients undergoing
low-density lipoprotein apheresis with
dextran sulfate absorption).
Angioedema (angioedema of the face,
extremities, lips, tongue, glottis, and/or
larynx has been reported; angioedema
associated with laryngeal edema may
be fatal; intestinal angioedema has
been reported presenting with
Page | 83
CARDIOVASCULAR SYSTEM
abdominal pain with or without nausea
or vomiting).
Neutropenia or agranulocytosis
(agranulocytosis and bone marrow
depression have been reported;
consider periodic monitoring of WBC
counts).
Hepatic impairment (associated with a
syndrome that starts with cholestatic
jaundice and progresses to fulminant
hepatic necrosis, and sometimes,
death; may precipitate hepatic coma)
Renal disease (may precipitate azotemia).
Ophthalmic effects (can cause idiosyncratic
reactions; acute myopia and secondary
angle-closure glaucoma have been
reported).
Adverse Drug Reactions:
Common: Dizziness, headache, fatigue,
cough, muscle cramps, nausea,
asthenia, orthostatic effects,
impotence, diarrhea
Less Common: Syncope, chest pain,
abdominal pain, orthostatic
hypotension, palpitation, tachycardia,
vomiting, dyspepsia, constipation,
flatulence, dry mouth, insomnia,
nervousness, paresthesia,
somnolence, vertigo, pruritus, rash,
dyspnea, gout, back pain, arthralgia,
diaphoresis, decreased libido, tinnitus,
urinary tract infection, angioedema,
hypotension, cough.
Administration:
Take once daily in the morning. If to be taken
twice daily, take the first dose in the
morning and the second dose before 6
in the evening.
See General Information under Agents Acting
on the Renin-Angiotensin System – ACE
Inhibitors, Plain in Chapter 3:
Cardiovascular System for information
on Warnings and Precautions.
Pregnancy Category: D
Page | 84
ATC Code: C09BA02; C03AX01
ANGIOTENSIN II ANTAGONISTS, PLAIN
GENERAL INFORMATION
Also known as Angiotensin Receptor Blockers
(ARB), they act by blocking the type 1
angiotensin II (AT1) receptors on blood
vessels and other tissues such as the heart,
which prevents the stimulation of vascular
smooth muscle contraction
Precautions:
WARNING: Fetal Toxicity. Drugs acting
directly on the renin-angiotensin system can
cause injury and death to the developing
fetus. When pregnancy is detected,
discontinue as soon as possible.
Peripheral vascular disease (patients may be
more likely to have renal artery stenosis)
Volume or sodium depletion (may activate the
renin-angiotensin system leading to
excessive hypotension) Aortic or mitral valve
stenosis and hypertrophic cardiomyopathy;
angioedema (may occur rarely; may involve
head and neck or the intestine)
Hypotension (symptomatic hypotension may
occur upon initiation in patients who are
salt- or volume-depleted); Heart failure
Hyperkalemia; renal function deterioration
(increased risk of hyperkalemia);
Hepatic impairment
Renal artery stenosis (avoid use in patients
with unstented unilateral or bilateral renal
artery stenosis).
Surgical patients (if on chronic ARB therapy,
intraoperative hypotension may occur with
induction and maintenance of general
anesthesia).
Elderly (may be volume-depleted due to
diuretic use and/or blunted thirst reflex
resulting in inadequate fluid intake).
Pregnancy (avoid use unless essential; may
adversely affect fetal and neonatal BP
control and renal function)
 CARDIOVASCULAR SYSTEM
Lactation (not known if excreted into Aliskiren (also hypotensive, and
breastmilk; information is limited). nephrotoxic effects), Potassium
Supplements, Drugs that cause
NOTE: Concomitant use of an ACE inhibitor or Potassium retention, e.g., Potassium-
renin inhibitor, e.g., Aliskiren, is associated sparing Diuretics, Spironolactone
with an increased risk of hypotension, Drugs whose risk of adverse or toxic effects
hyperkalemia, and renal dysfunction. (hypotensive effect) may be increased -
ACE Inhibitors e.g. Enalapril, Ramipril,
Drug Interactions: Rituximab, Sodium Phosphates (also
Monitor closely with: nephrotoxic effect, specifically acute
Drugs that decrease the metabolism of ARB: phosphate nephropathy)
Agents, e.g., Azole Derivatives, (Systemic), Drugs whose serum concentration may be
CYP2C8 Substrates, CYP2C9 Substrates increased -
Drugs that enhance the therapeutic effect ACE Inhibitors e.g. Enalapril,
(antihypertensive effect) of ARB: Amodiaquine, Lithium, Ramipril
Alfuzosin, Barbiturates e.g. Phenobarbital, [Ramiprilat]
Brimonidine (Topical), Canagliflozin,
Diazoxide, MAO Inhibitors [except NOTE: Dual blockade of the Renin-Angiotensin-
Linezolid], NSAIDs, Other Aldosterone system, i.e., ARB and ACEI
Antihypertensive Agents, Pentoxifylline, combination, in patients with established
Phosphodiesterase-5 Inhibitors e.g. heart failure, atherosclerotic disease, or
Sildenafil, Prostacyclin Analogues diabetes with end-organ damage is
Drugs that increase the risk of adverse or toxic associated with higher risk for
effects of ARB: hypotension, syncope, hyperkalemia, and
Antifungal Agents, e.g., Azole Derivatives, disordered renal function, including acute
(Systemic) Hyperkalemic effect: renal failure.
Canagliflozin, Heparin, NSAIDS (also
acute renal failure), Tolvaptan,
Trimethoprim Orthostatic hypotension:
MAO Inhibitors [except Linezolid,] First LOSARTAN
ARB dose hypotension: Loop diuretics, Rx
Thiazide diuretics Other Antihypertensive
Agents
Drugs whose risk of adverse or toxic effects Oral.: 50 mg and 100 mg tablet (as potassium
may be increased - salt)
Ciprofloxacin (systemic) (arrhythmogenic
effect), Cyclosporine (systemic) An angiotensin II type 1 (AT1) receptor blocker
(hyperkalemic effect), Duloxetine whose efficacy in hypertension is similar to that
(orthostatic hypotension), Levodopa of ACE inhibitors but is associated with a lower
(orthostatic hypotension), Risperidone incidence of side effects, such as dry cough
(hypotensive effect) and angioedema.
Drugs that reduce the therapeutic effect of
Indications: Treatment of hypertension.
ARB:
Methylphenidate, Rifampicin
Contraindications:
Concomitant use with aliskiren in patients with
Avoid concomitant use with
diabetes mellitus
Drugs that increase the risk of adverse or toxic
Dose:
effects (hyperkalemia) of ARB:

Page | 85
CARDIOVASCULAR SYSTEM
Hypertension, by mouth, ADULT, usual starting
dose, 50 mg once daily; can be
administered once or twice daily with a
total daily dose ranging from 25–100 mg
(usual initial dose in patients receiving
diuretics, or those with intravascular
volume depletion: 25 mg once daily).
Dose Adjustments:
Hepatic impairment: For mild-to-moderate
hepatic impairment, dose reduction is
warranted. For severe impairment,
refer the patient to a specialist.
Renal impairment: For severe impairment,
refer the patient to a specialist.
Precautions
WARNING: Fetal Toxicity. Drugs acting
directly on the renin-angiotensin system can
cause injury and death to the developing
fetus. When pregnancy is detected,
discontinue as soon as possible.
Adverse Drug Reactions:
Common: Dizziness, fatigue, headache,
hyperkalemia, hypoglycemia, nausea,
upper respiratory tract infections,
urinary tract infections
Less Common: Abnormal liver function, angina,
back pain, decreased hemoglobin,
diarrhea, dyspepsia, dyspnea, edema,
hypotension (first-dose), insomnia,
malaise, muscle cramps, myalgia,
nasal congestion, palpitation,
pharyngitis, pruritus, rash, sleep
disorder
Rare: Anaphylaxis, anemia, angioedema, atrial
fibrillation, cerebrovascular accidents,
cough, depression, erectile
dysfunction, hepatitis, hyponatremia,
pancreatitis, purpura, renal
impairment, rhabdomyolysis, syncope,
thrombocytopenia, vasculitis
Administration:
May be taken with or without food.
Page | 86
The patient may feel dizzy when taking this
medicine. Advise patient to get up
gradually from sitting or lying position to
minimize this effect. and sit or lie down
if the patient becomes dizzy or light-
headed.
See for General Information under Agents
Acting on the Renin-Angiotensin
System – Angiotensin II Antagonists,
Plain in Chapter 3: Cardiovascular
System for other information.
Pregnancy Category: C in 1st trimester; D in
2nd and 3rd trimesters
ATC Code: C09CA01
LOSARTAN +
Rx HYDROCHLOROTHIAZIDE
Oral.: 50 mg losartan + 12.5 mg
hydrochlorothiazide tablet
Losartan is an angiotensin II type 1 (AT1)
receptor blocker whose efficacy in
hypertension is similar to that of ACE
inhibitors but is associated with a lower
incidence of side effects, such as dry
cough and angioedema.
Hydrochlorothiazide inhibits sodium
reabsorption in the distal tubules causing
increased excretion of sodium and water,
as well as potassium and hydrogen ions
Indications: Treatment of hypertension.
Contraindications: Hypersensitivity to
sulfonamide-derived drugs; concomitant
use with aliskiren in patients with
diabetes mellitus; anuria
Dose:
NOTE: Individualize doses. Combination
products may be substituted for individual
CARDIOVASCULAR SYSTEM
components in patients currently
maintained on both agents separately or
in patients not adequately controlled with
monotherapy.
Hypertension, replacement therapy, by mouth,
ADULT, 1–2 tablets (50–100 mg losartan
+ 12.5–25 mg hydrochlorothiazide) once
daily, may titrate dose after approximately
3 weeks of therapy as necessary until the
maximum daily dose is reached
(maximum daily dose, 100 mg losartan +
25 mg hydrochlorothiazide).
Severe hypertension, by mouth, ADULT, initially
1 tablet (50 mg losartan + 12.5 mg
hydrochlorothiazide) once daily, may
titrate dose after 2–4 weeks of therapy as
necessary until the maximum daily dose is
reached (maximum daily dose, 2 tablets:
100 mg losartan + 25 mg
hydrochlorothiazide).
Hypertension with left ventricular hypertrophy,
by mouth, ADULT, 1 tablet (50 mg losartan
+ 12.5 mg hydrochlorothiazide) once
daily, may increase to 2 tablets (100 mg
losartan + 12.5 mg hydrochlorothiazide
once daily).
NOTE: Initiate treatment with losartan
monotherapy. If blood pressure reduction
is inadequate, initiate losartan +
hydrochlorothiazide combination.
Dose Adjustments:
Renal impairment: In severe impairment (CrCl
≤30 mL/min), use is not recommended
and is ineffective.
Hepatic impairment: Use is not recommended
as initial therapy.
Precautions:
WARNING: Fetal Toxicity. Drugs acting
directly on the renin-angiotensin system can
cause injury and death to the developing
fetus. When pregnancy is detected,
discontinue as soon as possible.
Adverse Drug Reactions:
Common: Edema, palpitation, dizziness, skin
rash, abdominal pain, back pain, upper
respiratory infection, cough, sinusitis
Less Common: hypertension or hypotension,
hyponatremia, rhabdomyolysis, thrombo-
cytopenia
Administration: May be administered without
regard to meals.
See individual monographs for Losartan under
Agents Acting on the Renin-Angiotensin
System – Angiotensin II Antagonists, Plain
in Chapter 3: Cardiovascular System and
Hydrochlorothiazide under Diuretics –
Thiazide Diuretics in Chapter 3:
Cardiovascular System for other
information.
Pregnancy Category: D
ATC Code: C09DA01; C03AX01
BETA-BLOCKING AGENTS
BETA-BLOCKING AGENTS, SELECTIVE
GENERAL INFORMATION
Selective beta-blockers (cardio-selective)
exhibit a competitive inhibitory effect on
beta1adrenergic receptors, with little or
no effect on beta2receptors, except at
high doses.
Mode of Action: Competitively inhibits beta1-
adrenergic receptors, preventing the
action of norepinephrine and epinephrine
on these receptors. Beta1-adrenergic
receptors are primarily located in the
heart. Their activity causes a reduction in
sympathetic influences, including
chronotropic (heart rate), inotropy
Page | 87
CARDIOVASCULAR SYSTEM
(contractility), dromotropy (electrical
conduction), and lusitropy (relaxation).
Contraindications: Reversible airway diseases;
second- or third-degree heart block
(except in patients with functioning
artificial pacemaker); shock (cardiogenic
and hypovolemic); bradycardia (45 to 50
beats/minute); sick sinus syndrome
(except in the presence of a pacemaker);
severe hypotension; uncontrolled heart
failure; concomitant IV administration of
calcium channel blockers; pulmonary
hypertension
Precautions:
WARNING:
Do NOT withdraw beta-blocker therapy
abruptly. Gradually taper over 1–2 weeks to
avoid acute tachycardia, hypertension,
and/or ischemia. Abrupt withdrawal may
exacerbate angina and, in some cases,
cause myocardial infarction, ventricular
arrhythmias, and rebound hypertension.
Temporary but prompt resumption of beta-
blocker therapy may be indicated with
worsening of angina or acute coronary
insufficiency.
Major surgery: Do NOT withdraw chronic
beta-blocker therapy before major surgery.
Atrial fibrillation; Atrioventricular block
(commonly produces mild first-degree heart
block; may also produce severe first- (P-R
interval ≥0.26 sec), second-, or third-degree
heart block); patients with acute myocardial
infarction have a high risk of developing
heart block of varying degrees)
Hypotension (symptomatic hypotension may
occur with use)
Anaphylactic reactions (may become more
sensitive to repeated challenges; treatment
of anaphylaxis, e.g., epinephrine, may be
ineffective or even promote undesirable
effects)
Extravasation (can lead to skin necrosis and
sloughing)
Page | 88
Hyperkalemia (associated with elevations in
serum potassium and development of
hyperkalemia; monitor serum potassium
during therapy); hepatic impairment.
Bronchospastic disease (maybe exacerbated)
Conduction abnormality (can cause
bradycardia, including sinus pause, heart
block, severe bradycardia, and cardiac
arrest)
Diabetes (may potentiate and/or mask signs
and symptoms of hypoglycemia)
Heart failure (monitor for worsening of
condition).
Myasthenia gravis
Peripheral vascular disease and Raynaud’s
disease (can precipitate or aggravate
symptoms or arterial insufficiency)
Pheochromocytoma (may aggravate
hypertension; requires adequate alpha
blockade before use of beta-blockers)
Prinzmetal variant angina (requires
concomitant alpha1- adrenergic receptor
blockage, unopposed alpha1- adrenergic
receptors mediate coronary
vasoconstriction and can worsen angina
symptoms).
Psoriasis (associated with induction or
exacerbation of psoriasis)
Psychiatric disease (may cause or exacerbate
CNS depression)
Renal impairment (active metabolite is
retained); thyroid disease (may mask signs
of hyperthyroidism, e.g., tachycardia; abrupt
withdrawal may exacerbate symptoms of
hyperthyroidism and precipitate a thyroid
storm; may alter thyroid function tests).
Elderly (bradycardia may be observed more
frequently in patients >65 years).
Pregnancy (crosses the placenta; may cause
intrauterine growth restriction, small
placenta, fetal or neonatal bradycardia,
hypoglycemia, respiratory depression);
lactation (excreted in breast milk and
detected in the serum and urine of nursing
infants; use with caution).
Adverse Drug Reactions:
Common: Alteration of glucose and lipid
metabolism, bradycardia, bronchospasm,
CARDIOVASCULAR SYSTEM
cold extremities, depression, diarrhea, negative inotropic effect), Other
dizziness, dyspepsia, dyspnea, Antihypertensives, Pentoxifylline,
exacerbation of Raynaud’s phenomenon, Phosphodiesterase-5 Inhibitors e.g.,
fatigue, hallucinations, first-degree heart Sildenafil, Prostacyclin Analogues,
block (P-R interval ≥0.26 seconds), heart Reserpine; Propafenone (possesses
failure, hypotension, nausea, pruritus, independent beta-blocking activity)
second and third-degree heart block, Drugs whose therapeutic effect may be
shortness of breath, tiredness, syncope, enhanced:
vomiting, wheezing Bradycardic effect: Fingolimod, Ivabradine,
Less Common: Acute urinary retention, anxiety, Midodrine
cardiogenic shock, chest pain, Hypoglycemic effect: Insulin, Sulfonylureas
claudication, confusion, constipation, e.g., Gliclazide Lacosamide (AV blocking
flatulence, gastric pain, headache, effect)
heartburn, hyperhidrosis, impaired Drugs whose risk of adverse or toxic effects
concentration, impotence, insomnia, may be increased by Beta Blockers -
muscle cramps, nasal congestion, Amiodarone (cardiac arrest), Calcium
nervousness, nightmares, palpitations, Channel Blockers, Non-Dihydropyridine
peripheral edema, Peyronie’s disease, [except Bepridil] (bradycardia; signs of heart
rash, reduced libido, sleep disturbances, failure), MAO Inhibitors [except Linezolid]
somnolence, taste disturbance, urticaria, (orthostatic hypotension), Other
visual disturbances, vertigo, xerostomia Antihypertensive Agents
Rare: Agranulocytosis, alopecia, arthritis, Drugs whose risk of adverse or toxic effects
blurred vision, cardiac arrest, catatonia, may be increased:
emotional lability, exacerbation of Cardiac Glycosides (bradycardic effect);
psoriasis, gangrene, hepatitis, Cholinergic Agonists (cardiac conduction
hypersensitivity reaction, jaundice, abnormalities; bronchoconstriction);
laryngospasm, liver function abnormality, Duloxetine (orthostatic hypotension)
respiratory distress, retroperitoneal Levodopa (orthostatic hypotension); MAO
fibrosis, thrombocytopenia, Inhibitors [except Linezolid,] (orthostatic
thrombocytopenic purpura, tinnitus hypotension) Risperidone (hypotensive
effect)
Drug Interactions: Reduce the therapeutic effect of Beta-
Monitor closely with: Blockers:
Drugs that decrease the metabolism of Beta- Nonsteroidal Anti-Inflammatory Agents
Blockers: Aminoquinolines e.g., Antimalarial (antihypertensive effect)
drugs Drugs whose therapeutic effect may be
Drugs that enhance the therapeutic effect of reduced:
Beta-Blockers: Beta2 Agonists (bronchodilatory effect);
Bradycardic effect: Acetylcholinesterase Theophylline Derivatives (bronchodilatory
Inhibitors e.g., Neostigmine, Amiodarone; effect)
Opioids e.g., Fentanyl (bradycardic and
antihypertensive effects),), Dipyridamole, Avoid concomitant use with:
Disopyramide (also negative inotropic Drugs that enhance the therapeutic effect of
effect), Other Bradycardia-causing Agents Beta-Blockers: Alpha2 Agonists (AV
Antihypertensive effect: Barbiturates e.g., blocking effect), Bradycardic effect:
Phenobarbital, Brimonidine (Topical), Dronedarone, Rivastigmine
Calcium Channel Blockers, Non- Drugs that increase risk of adverse or toxic
Dihydropyridine [except Bepridil] e.g., effects of Beta-Blockers:
Verapamil, Diazoxide, Nifedipine (also CYP2D6 Inhibitors (heart block)
Page | 89
CARDIOVASCULAR SYSTEM
Drugs that increase the serum concentration
of Beta-Blockers:
CYP2D6 Inhibitors, Dronedarone
Drugs whose risk of adverse or toxic effects
may be increased -
Alpha1 Blockers (orthostatic
hypotension), Alpha2 Agonists (rebound
hypertension; sinus node dysfunction),
Grass Pollen Allergen Extract / 5 Grass
Extract (inhibits the ability to effectively
treat severe allergic reactions with
Epinephrine) Methacholine, Rituximab
(hypotensive effect) I
Drugs whose therapeutic effect may be
reduced:
Alpha / Beta Agonists, Direct-Acting
[except Dipivefrin] (beta-adrenoceptor
mediated effects, including anti
anaphylactic effects of Epinephrine)
Drugs whose therapeutic effect may be
reduced -
Alpha / Beta Agonists, Direct-Acting [except
Dipivefrin] (vasopressor effect); Ceritinib
(bradycardic effect); Ergot Derivatives
(vasoconstricting effect)
METOPROLOL
Rx (AS TARTRATE)
Oral.: 50 mg and 100 mg tablet
A beta1-selective antagonist that competitively
blocks beta1- adrenergic stimulation, with little
or no effect on beta2- receptors except at high
doses. It exhibits no intrinsic sympathomimetic
activity (ISA).
Indications: Treatment of hypertension, alone
or in combination with other agents;
management of angina pectoris; secondary
prevention post-myocardial infarction; for
the acute coronary syndrome
Dose:
Hypertension, by mouth, ADULT, initially 25–
50 mg once daily, may increase to 100 mg
Page | 90
once daily after 1–2 weeks (usual dose,
100 mg once daily; target dose, 100 mg
once daily); CHILD, 0.5–1 mg/kg per dose
daily; usual dosage range, 0.5 to 1.5
mg/kg daily (maximum dose, 2 mg/kg
daily for up to 100 mg daily).
Angina pectoris, by mouth, ADULT, 50 mg once
daily; may increase to 100 mg daily; some
patients may require 200 mg daily.
Post-myocardial infarction, by mouth, ADULT,
100 mg daily or 50 mg twice daily for 6–9
days post-myocardial infarction.
Dose Adjustments:
Geriatric: In the management of hypertension,
consider lower initial doses and titrate
to the response.
Renal impairment: If CrCl is 15–35 mL/minute
per 1.73m2, the maximum dose is 50
mg daily.
If CrCl is <15 mL/min per 1.73m2 maximum
dose is 25 mg daily
For patients on hemodialysis, administer dose
post-dialysis or administer 25–50 mg
supplemental dose. Atenolol is
moderately dialyzable (20% to 50%) via
hemodialysis.
Precautions:
WARNING:
Do NOT withdraw beta-blocker therapy
abruptly. Gradually taper over 1–2 weeks to
avoid acute tachycardia, hypertension,
and/or ischemia. Abrupt withdrawal may
exacerbate angina and, in some cases,
cause myocardial infarction, ventricular
arrhythmias, and rebound hypertension.
Temporary but prompt resumption of beta-
blocker therapy may be indicated with
worsening of angina or acute coronary
insufficiency.
Major surgery: Do NOT withdraw chronic
beta-blocker therapy before major surgery.
Administration: May be taken without regard to
meals.
NOTE: When administered acutely, monitor
ECG and blood pressure.
CARDIOVASCULAR SYSTEM
See General Information on Beta Blocking
Agents, Selective listed above for other
information.
Pregnancy Category: D
ATC Code: C07AB03
ATENOLOL
Rx
Oral.: 50 mg and 100 mg tablet
A beta1-adrenoceptor (cardio-selective)
antagonist without intrinsic
sympathomimetic activity (ISA), which
may be advantageous in treating
hypertensive patients who also suffer
from asthma, diabetes, or peripheral
vascular disease.
Indications: Management of hypertension;
angina pectoris; acute coronary
syndrome; post-myocardial infarction
maintenance
Dose:
Angina, by mouth, ADULT, initially 50 mg twice
daily; usual dosage range is 50–200 mg
twice daily (maximum dose, 400 mg
daily); increase the dose gradually at
weekly intervals to achieve the desired
effect.
Hypertension, by mouth, ADULT, initially 50 mg
twice daily; effective dosage range is
100–450 mg daily in 2–3 divided doses;
increase dose at weekly intervals to
desired effect (maximum total daily dose,
450 mg; usual dosage range, 50–100 mg
twice daily; target dose, 100– 200 mg
daily); CHILD 1–17 years, initially 1–2
mg/kg daily (maximum dose, 6 mg/kg
daily (≤200 mg daily); administer in 2
divided doses.
Myocardial infarction, early treatment, by
mouth, ADULT, 25–50 mg every 6–12
hours; transition over the next 2– 3 days
to twice-daily dosing and increase as
tolerated to a maximum daily dose of 200
mg.
NOTE: The ACCF/AHA guidelines for the
management of STEMI recommend
initiation within the first 24 hours. Do not
initiate this regimen in those with signs of
heart failure, a low output state, increased
risk of cardiogenic shock, or other
contraindications.
Myocardial infarction, secondary prevention,
by mouth, ADULT, 25–100 mg twice daily;
optimize dose based on heart rate and
blood pressure; continue indefinitely.
Dose Adjustments:
Geriatric: In the management of hypertension,
consider lower initial doses and titrate
to the response.
Renal impairment: For mild-to-moderate
impairment, no dose adjustment is
necessary. For severe impairment,
refer the patient to a specialist.
Hepatic impairment: For mild-to-moderate
impairment, dose reduction may be
warranted For severe impairment, refer
the patient to a specialist.
Precautions:
WARNING:
Do NOT withdraw beta-blocker therapy
abruptly. Gradually taper over 1–2 weeks to
avoid acute tachycardia, hypertension, and/or
ischemia. Abrupt withdrawal may exacerbate
angina and, in some cases, cause myocardial
infarction, ventricular arrhythmias, and
rebound hypertension. Temporary but prompt
resumption of beta-blocker therapy may be
indicated with worsening of angina or acute
coronary insufficiency
Major surgery: Do NOT withdraw chronic beta-
blocker therapy before major surgery.
Administration: To be taken with or
immediately following food intake.
Page | 91
CARDIOVASCULAR SYSTEM
See General Information on Beta Blocking Hypotension (poor cardiac function if given
Agents, Selective listed above for other with other cardio depressant drugs);
information congestive heart failure; aortic stenosis;
pre-existing abnormalities in the sinoatrial
Pregnancy Category: C and/or atrioventricular node (increased
angina or MI can develop after starting or
ATC Code: C07AB02 increasing the dose, particularly in
patients with severe obstructive coronary
artery disease).
Hepatic impairment (half-life prolonged); Acute
CALCIUM CHANNEL
porphyria
BLOCKERS Increased intracranial pressure;
Glaucoma;
Pregnancy (limited information on use in
SELECTIVE CALCIUM CHANNEL humans; risk to fetus should be balanced
BLOCKERS WITH MAINLY VASCULAR against the risk of uncontrolled maternal
EFFECTS hypertension); lactation (presence in milk
is possible; monitor infant).

AMLODIPINE Adverse Drug Reactions:

Rx Common: Abdominal pain, dizziness, fatigue,
flushing, gingival hyperplasia, headache,
nausea, palpitation, peripheral edema,
Oral.: 5 mg and 10 mg tablet pulmonary edema, rash, sleep disturbances
Less Common: Arthralgia, dryness of mouth,
A long-acting dihydropyridine, calcium channel chest pain, constipation, dyspepsia, dyspnea,
blocker (CCB), that is used for GI disturbances, gynecomastia, hypotension,
hypertension and coronary artery disease. impotence, myalgia, paresthesia, polyuria,
mood changes, pruritus, pulmonary edema,
Indications: Management of hypertension sweating, syncope, tachycardia, taste
disturbances, tinnitus, tremor, urinary
disturbances, weight changes
Contraindications: unstable angina;
Rare: Agitation, alopecia, amnesia,
cardiogenic shock; hypotension;
angioedema, arrhythmias, ataxia, cardiac
significant aortic stenosis; in instances of failure, cholestasis, coughing, dermatitis,
MI with heart failure or poor LV function erythema multiforme, gastritis, hepatitis,
hyperglycemia, myocardial infarction,
Dose: pancreatitis, Parkinsonism, parosmia,
Hypertension, by mouth, ADULT, initially 2.5 jaundice, peripheral neuropathy, purpura,
mg once daily, increased if necessary thrombocytopenia, twitching, vasculitis,
(maximum dose, 10 mg once daily); abnormal visual accommodation,
CHILD, refer to a specialist. xerophthalmia

Dose Adjustments: Drug Interactions:

Hepatic impairment In patients with hepatic Monitor closely with:
insufficiency, consider dose reduction, Drugs that enhance the therapeutic effect of
initiating with 2.5 mg daily. In patients Amlodipine:
with severe impairment, titrate slowly. Drugs that reduce blood pressure (enhanced
hypotensive effects)
Precautions:

Page | 92
CARDIOVASCULAR SYSTEM
Avoid concomitant use with:
Calcium salts - Reduces the therapeutic effect
of Amlodipine:
Simvastatin [limit Simvastatin dose to 20 mg
daily] (myopathy) –Amlodipine increases
the serum concentration of these drugs,
increasing its risk of adverse or toxic
effects:
Administration: May be taken with or without
food.
Pregnancy Category: C
ATC Code: C08CA01
NICARDIPINE
Rx
Inj.: 1 mg/mL (as hydrochloride), 2 mL and
10 mL ampule (IV)
A calcium channel blocker that inhibits calcium
ions from entering select voltage-sensitive
areas of vascular smooth muscle and
myocardium. It produces relaxation of
coronary vascular smooth muscle and
coronary vasodilation, thus increasing
myocardial oxygen delivery in patients with
vasospastic angina.
Indication: Management of acute severe
hyper- tension
Contraindications: Advanced aortic stenosis
Dose:
Acute severe hypertension, by IV infusion,
ADULT, 5 mg/ hour initially, may increase
by 2.5 mg/hour every 5 minutes for rapid
titration, to every 15 minutes for gradual
titration (maximum dose, 15 mg/hour); in
rapidly titrated patients, consider
reduction to 3 mg/hour after the response
is achieved
Dose Adjustment:
Geriatric: Initiate at the low end of the dosage
range. Monitor closely.
Renal and Hepatic Impairment: Dose
adjustment may be necessary. Titrate
slowly with careful monitoring. Consider
lower starting dose and closely monitor
response.
Precautions:
WARNING: Significant differences exist
between oral and IV dosing. Use caution
when converting from one route of
administration to another.
Angina, myocardial infarction (increased
frequency, duration, or severity of angina
and/or MI has occurred with initiation or
dosage titration; reflex tachycardia may
occur);
Hypotension; Syncope (rarely occurs);
Peripheral edema (dose-dependent);
Tachycardia (may occur).
Aortic stenosis (may reduce coronary perfusion
resulting in ischemia)
Heart failure (may worsen symptoms of HF due
to mild negative inotropic effects of
nicardipine, particularly with concomitant
beta-blockade)
Hypertrophic cardiomyopathy with outflow
tract obstruction (reduction in afterload may
worsen symptoms associated with this
condition)
Hepatic impairment; Renal impairment
Abrupt withdrawal may cause rebound angina
in patients with CAD
Elderly (constipation may be more of a
problem; may experience greater
hypotensive response)
Pregnancy (adverse events have been
observed in some animal reproduction
studies; crosses the placenta; changes in
fetal heart rate, neonatal hypotension, and
neonatal acidosis have been observed
following maternal use); lactation (minimally
excreted in breastmilk; breast­feeding is not
recommended).
Adverse Drug Reactions:
Common: Flushing, pedal edema,
exacerbation of angina pectoris,
Page | 93
CARDIOVASCULAR SYSTEM
hypotension, palpitations, tachycardia,
chest pain, extrasystoles,
hemopericardium, supraventricular
tachycardia, hypertension, edema,
headache, dizziness, hypoesthesia,
intracranial hemorrhage, pain, somnolence,
diaphoresis, skin rash, hypokalemia,
nausea, vomiting, dyspepsia, abdominal
pain, xerostomia, hematuria, injection site
reaction, pain at the injection site,
weakness, myalgia, paresthesia
Less Common: Abnormal dreams, abnormal
vision, angina pectoris, anxiety, atrial
fibrillation, atrioventricular block, arthralgia,
atypical chest pain, blurred vision, cerebral
ischemia, confusion, conjunctivitis,
constipation, deep vein thrombophlebitis,
depression, ST segment depression,
dyspnea, ear disease, fever, gingival
hyperplasia, heart block, hot flash,
hyperkinesia, hypersensitivity reaction,
hypophosphatemia, hypertonia, impotence,
infection, insomnia, inversion T wave on
ECG, malaise, myocardial infarction, neck
pain, nervousness, nocturia, orthostatic
hypotension, parotitis, pericarditis,
peripheral vascular disease, respiratory
tract disease, rhinitis, sinus node
dysfunction, sinusitis, sore throat,
sustained tachycardia, syncope,
thrombocytopenia, tinnitus, tremor, urinary
frequency, ventricular extrasystoles,
ventricular tachycardia, vertigo, vomiting
Drug Interactions:
Monitor closely with:
Drugs that decrease the metabolism of
Nicardipine:
Cyclosporine (Systemic), CYP2C19
Substrates, CYP2D6 Substrates
Drugs that enhance therapeutic effects of
Nicardipine:
Antihypertensive effect: Alpha1 Blockers
e.g. Alfuzosin, Barbiturates e.g.
Phenobarbital, Brimonidine (Topical), Non-
Dihydropyridine Calcium Channel Blockers,
Diazoxide, Magnesium Salts, Pentoxifylline,
Phosphodiesterase-5 Inhibitors e.g.
Page | 94
Sildenafil, Prostacyclin Analogues, Other
Antihypertensive Agents
Moderate Risk QTc-prolonging Agents,
Indeterminate Risk and Risk Modifying
(QTc-prolonging agents)
Drugs whose therapeutic effects are
enhanced by Nicardipine:
Aripiprazole, Carvedilol (hypotensive
effect), Nondepolarizing Neuromuscular-
blocking Agents e.g. Pancuronium
(neuromuscular-blocking effect),
Nitroprusside (hypotensive effect)
Drugs that increase the metabolism of
Nicardipine:
Barbiturates e.g., Phenobarbital
Drugs that increase risk of adverse or toxic
effects of Nicardipine:
MAO Inhibitors [except Linezolid]
(orthostatic hypotension), Other
Antihypertensive Agents
Drugs whose risk of adverse or toxic effects
are increased by Nicardipine:
Carvedilol (may precipitate signs of heart
failure), Duloxetine (orthostatic
hypotension), Levodopa (orthostatic
hypotension), Magnesium Salts,
Risperidone (hypotensive effect)
Drugs that reduce the therapeutic effect of
Nicardipine:
Barbiturates e.g., Phenobarbital, Calcium
Salts, Methylphenidate
Drugs whose therapeutic effects are reduced:
Codeine (prevents metabolic conversion to
its active metabolite, morphine); Tramadol
(prevents metabolic conversion to its
active metabolite)
Avoid concomitant use with:
Drugs that decrease the metabolism of
Nicardipine:
Antifungal Agents, Azole Derivatives,
Systemic [except Fluconazole], CYP2C9
Substrates, CYP3A4 Inhibitors; Macrolide
Antibiotics [except Azithromycin]
Drugs that decrease the serum concentration
of Nicardipine:
Efavirenz, Phenytoin, Rifamycin Derivatives
Drugs whose serum concentration may be
decreased:
Clopidogrel, Tamoxifen
Drugs whose therapeutic effects may be
enhanced:
CARDIOVASCULAR SYSTEM
Highest Risk QTc-prolonging Agents,
Indeterminate Risk and Risk Modifying
(QTc-prolonging effect)
Drugs that enhance the therapeutic effect of
Nicardipine:
Mifepristone (QTc-prolonging effect)
Drugs that increase the metabolism of
Nicardipine:
Carbamazepine, CYP3A4 Inducers, Nafcillin
Drugs that increase risk of adverse or toxic
effects of Nicardipine:
Azole Antifungal Agents (Systemic) [except
Fluconazole,] (negative inotropic effects),
Grapefruit Juice
Drugs whose risk of adverse or toxic effects
may be increased:
Citalopram (serotonin syndrome; QT
prolongation), Highest Risk QTc-prolonging
Agents, Indeterminate Risk and Risk
Modifying (alterations of cardiac rhythm),
Phenytoin, Rituximab (hypotensive effect)
Drugs that increase the serum concentration
of Nicardipine:
Fusidic Acid (Systemic), Grapefruit Juice,
Drugs whose serum concentration may be
increased:
Cilostazol [reduce Cilostazol dose to 50 mg
twice daily], Citalopram [limit Citalopram
dose to a maximum of 20 mg daily],
Colchicine (increases distribution into
certain tissues, e.g., brain), Dabigatran
Etexilate, Diclofenac (Systemic),
Doxorubicin (Conventional), Everolimus,
Lacosamide, Metoprolol, Pazopanib,
Phenytoin, Vincristine (Liposomal)
Drugs that reduce the therapeutic effect of
Nicardipine:
Phenytoin
Drugs whose therapeutic effect may be
reduced:
Clopidogrel
Administration:
Administer by slow continuous IV infusion via a
central line or through a large peripheral
vein. Avoid the use of small peripheral veins
to minimize infusion site reactions.
Do NOT combine or run in the same line as
other medications.
Monitor infusion site closely to prevent
extravasation. Peripheral venous irritation
may be minimized by changing the site of
infusion every 12 hours.
Evaluate cardiac status and blood pressure
and monitor for rash, hypotension,
bradycardia, confusion, and nausea when
starting, adjusting the dose, or
discontinuing.
NOTE: Parenteral administration is indicated
only for short-term use.
Teach patient orthostatic precautions.
Pregnancy Category: C
ATC Code: C08CA04
SELECTIVE CALCIUM CHANNEL
BLOCKERS WITH DIRECT CARDIAC
EFFECTS
GENERAL INFORMATION
Selective calcium-channel blockers (CCBs)
exhibit an inhibitory effect on L-type calcium
channels. It is used for the treatment of
hypertension, angina, and arrhythmias.
Mode of Action: Binds to L-type calcium
channels located on the vascular smooth
muscle, cardiac myocytes, and cardiac nodal
tissue, blocking the entry of calcium into the
cell. This causes vascular smooth muscle
relaxation, decreased myocardial force
generation, decreased heart rate, and
decreased conduction velocity within the heart.
Precautions:
WARNING: All CCBs have some degree of
negative inotropic effect and may, in
excessive doses or in combination with
other drugs, produce myocardial
depression especially after MI.
Abrupt withdrawal and long-term use (have
been associated with severe angina).
Conduction abnormalities (may worsen first-
degree AV block and exacerbate
bradycardia); arrhythmia (severe
hypotension likely to occur upon
Page | 95
CARDIOVASCULAR SYSTEM
administration); heart failure (can
exacerbate the condition); impaired left
ventricular function; hypotension or
syncope (symptomatic hypotension with
or without syncope rarely occur);
Hypertrophic cardiomyopathy [HCM] with
outflow tract obstruction.
Hepatic and renal impairment (in severe
impairment, monitor hemodynamics, and
ECG);
Increased hepatic enzymes (rarely observed)
Diabetes mellitus (affects insulin secretion and
its peripheral action).
Attenuated neuromuscular transmission
(decreased neuromuscular transmission
has been reported).
Patients taking beta-blockers or digitalis (at
risk of AV block, bradycardia, asystole, or
sinus arrest);
Patients at risk to develop intestinal
obstruction (diltiazem has an inhibitory
effect on intestinal motility; may be
associated with mood changes).
Children (severe apnea, bradycardia,
hypotensive reactions, and cardiac arrest
may occur).
Elderly (greater hypotensive response;
constipation may be more of a problem)
Pregnancy (crosses the placenta; adverse
events were observed in some animal
reproduction studies); lactation (excreted
into breast milk; not recommended).
DILTIAZEM
Rx
Oral.: 30 mg and 60 mg tablet
60 mg, 90 mg, 120 mg, 180 mg MR
capsule
90 mg, 120 mg and 180 mg MR tablet
A non-dihydropyridine calcium channel
blocker, which has a negative chronotropic
effect, thus decreasing the workload of the
heart and consequently reducing its oxygen
requirements.
Page | 96
Indications: Prophylaxis and treatment of
angina
Dose:
Angina, by mouth, ADULT, initially 30 mg 3 or 4
times daily; increase as required or at 1- to
2-day interval until optimum response is
obtained (maximum dose, 360 mg daily in
3–4 divided doses); doses of up to 360
mg/day may be needed in unstable angina;
controlled-release products, initially 180 mg
once daily; increase as required up to 360
mg once daily.
NOTE: Dose should not be increased if the
heart rate drops to 50 beats/minute
Dose Adjustments:
Geriatric: Start treatment at a lower dose.
Renal impairment: Start treatment at a lower
dose. Use with caution
Hepatic impairment: For mild-to-moderate
hepatic impairment, dose reduction
may be warranted. For severe
impairment, refer the patient to a
specialist
Precautions:
WARNING: All CCBs have some degree of
negative inotropic effect and may, in
excessive doses or in combination with
other drugs, produce myocardial depression
especially after MI.
Adverse Drug Reactions:
Common: Abdominal pain, bradycardia,
dizziness, dyspnea, congestion, flushing,
headache, fatigue, nausea, nervousness,
pain, palpitations, peripheral edema,
vasodilation, vomiting
Less Common: AV block, gout
Rare: Depression, EPS, gum hyperplasia,
gynecomastia, hepatitis, hypersensitivity
reactions, photosensitivity reactions, rash
Drug Interactions:
Monitor closely with:
Drugs causing hypotension, bradycardia, or
slow cardiac conduction, e.g., Amlodipine,
CARDIOVASCULAR SYSTEM
Diazepam, Methyldopa;
Hydrochlorothiazide (bradycardia;
hypotension)- Increase the risk of adverse
or toxic effects of Diltiazem
Carbamazepine, Digoxin, Midazolam (sedative
and respiratory depressant effects; due to
decreased metabolism), Phenytoin,
Ritonavir (due to increased serum
concentration)- Increase the risk of
adverse or toxic effects
Rifampicin – Reduced therapeutic effect (due
to increased metabolism)
Avoid concomitant use with:
Colchicine, HMG-CoA Reductase Inhibitors,
e.g., Atorvastatin, Simvastatin
(rhabdomyolysis; myopathy)- Increased
risk of adverse or toxic effects due to
increased serum concentration:
Administration: Normal release preparations
may be taken with or without food.
Administer immediate-release
preparations before meals and at
bedtime. For long-acting dosage forms,
swallow whole. Do NOT open, chew, or
crush.
NOTE: Serum levels may be elevated if taken
with food.
See General Information on Calcium Channel
Blockers – Selective Calcium Channel
Blockers with Direct Cardiac Effects in
Chapter 3: Cardiovascular System for
other information.
Pregnancy Category: C
ATC Code: C08DB01
CENTRALLY ACTING
ANTIADRENERGIC AGENTS
CLONIDINE
Rx
Oral.: 75 micrograms tablet
An imidazoline-derived, centrally-acting agonist
at alpha2- adrenoceptors and imidazoline
receptors, which acts by reducing
sympathetic tone resulting in BP lowering.
Indications: Hypertension (alone or used
concomitantly with other antihypertensive
agents)
Contraindications: Bradyarrhythmia secondary
to second- or third-degree AV block or sick
sinus syndrome.
Dose:
NOTE: Individualize dose based on patient’s BP
response.
Hypertension, by mouth, ADULT, initially 75
micrograms 2– 3 times daily, increased by
75 micrograms daily every 2– 3 days
(maximum dose, 1.2 mg daily; maintenance
dose, 150–300 micrograms twice daily).
Hypertensive urgencies, by mouth, ADULT, 75
micrograms.
Dose Adjustments:
Renal impairment: Adjust dose according to
the degree of impairment. Patients may
benefit from a lower initial dose. For mild-to-
moderate impairment, use with caution. For
severe impairment, refer to a specialist.
Page | 97
CARDIOVASCULAR SYSTEM
Precautions: Common: Constipation, depression, dizziness,
WARNING: Severe withdrawal syndrome drowsiness, dry mouth, fatigue, headache,
(rebound HTN) may occur after abrupt malaise, nausea, orthostatic hypotension,
discontinuation. Sudden cessation of salivary gland pain, sedation, sexual
treatment has, in some cases, resulted in dysfunction, sleep disturbances, vomiting.
nervousness, agitation, headache, and
tremor accompanied or followed by a rapid Less Common: Bradycardia, confusion,
rise in BP and elevated catecholamine delusion, disturbed mental state,
concentration in the plasma.
hallucination, itching, nightmare, paresthesia,
pruritus, rash, urticaria.
Withdrawal syndrome (may be worsened by
concomitant administration of beta-
Rare: Alopecia, AV block, Colonic pseudo-
blockers; taper dose over 5–7 days before
obstruction, decreased lacrimation, dry eyes,
stopping the drug; excessive rise in BP
gynecomastia, hepatitis, impaired visual
following discontinuation can be reversed
accommodation, nasal dryness, Raynaud’s
by oral administration).
phenomenon, urinary retention.
Mild-to-moderate bradyarrhythmia,
constipation, or polyneuropathy (avoid
Drug Interactions:
use in patients with depression or a
Monitor closely with medicines that:
history of it); coronary heart disease,
Enhances therapeutic effect of Clonidine:
severe coronary insufficiency, conduction
CNS Depressants [e.g., Alcohol,
disturbances, recent MI, cerebrovascular
Barbiturates, Other Sedating Drugs], Drugs
disease, Raynaud’s phenomenon, or
that affect sinus node function or AV nodal
other vasospastic peripheral vascular
conduction [e.g., Digitalis, CCB (AV block;
disease (may be exacerbated).
bradycardia)]
CNS effects (may cause drowsiness; may
Increases risk of adverse or toxic effects of
increase effects of alcohol); diabetes
Clonidine:
mellitus (may cause a transient rise in
CNS Depressants [e.g., Alcohol,
blood glucose); renal impairment (may
Barbiturates, Other Sedating Drugs
worsen chronic renal failure). Surgery
(sedation; bradycardia; hypotension)], Drugs
(stopping abruptly may precipitate a
that reduce blood pressure and slow heart
severe withdrawal syndrome).
rate (bradycardia; hypotension)
Elderly (can cause drowsiness); children (may
be particularly susceptible to hypertensive
Avoid concomitant use with medicines that:
episodes resulting from an abrupt inability
Increases risk of adverse or toxic effects of
to take medication).
Clonidine:
Pregnancy (may lower fetal heart rate; risk
Beta-Blockers e.g., Propranolol (bradycardia;
should be balanced against the risk of
hypotension; paradoxical increase in BP),
uncontrolled maternal hypertension;
Drugs that reduce blood pressure and slow
avoid IV injection); lactation (avoid use if
heart rate (bradycardia; hypotension)
possible; limited data available; present in
Reduces the therapeutic effect of Clonidine:
breastmilk; may decrease prolactin
Tricyclic Antidepressants e.g., Amitriptyline
secretion).
(antihypertensive effect)
SKILLED TASKS. May impair the ability to drive
Administration:
or operate machinery due to drowsiness
If further increments are needed to produce
the desired response, take a larger portion
Adverse Drug Reactions:
of the oral daily dose at bedtime to minimize
drowsiness and dry mouth. Advise the
Page | 98
CARDIOVASCULAR SYSTEM
patient to get up gradually from sitting or intervals during the first 6– 12 weeks, or
lying to minimize this effect, and to sit or lie if unexplained fever occurs.
down if the patient becomes dizzy or light- History of depression (may be exacerbated).
headed. Renal impairment (increased sensitivity to
Pregnancy Category: C hypotensive and sedative effects);
Hepatic impairment (caution in history of
ATC Code: C02AC01 liver disease; avoid use if possible).
Lactation (amount in breastmilk is too small to
be harmful).

METHYLDOPA SKILLED TASKS. May impair the ability to drive

Rx or operate machinery due to drowsiness

Adverse Drug Reactions:

Oral.: 250 mg tablet Common: Diarrhea, dizziness, dryness of
mouth, fatigue, fever, headache, light-
A centrally-acting, alpha2-adrenoceptor headedness, positive Coombs’ test, sedation,
agonist that is useful in the management of tiredness, weakness.
hypertension in pregnancy. Less Common: Angina, bradycardia,
constipation, depression, edema, sodium and
Indications: For gestational hypertension and water or fluid retention, hemolytic anemia,
chronic hypertension in pregnant
impaired concentration, and memory,
women. decreased libido and impotence in men, nasal
congestion, orthostatic hypotension,
Contraindications: Pheochromocytoma; active
psychosis, rash, sleep disturbance, sore or
liver disease; depression, porphyria;
“black” tongue.
patients in whom previous methyldopa
Rare: Arthralgia, bone marrow depression,
treatment resulted in liver
hepatotoxicity with acute or chronic active
abnormalities, or direct Coombs’
hepatitis or hepatic necrosis,
positive hemolytic anemia
hyperprolactinemia, hypersensitivity reactions,
jaundice, leukopenia, myocarditis, nausea,
Dose:
pancreatitis, Parkinsonism, pericarditis,
Hypertension in pregnancy, by mouth, ADULT,
sialadenitis, stomatitis, thrombocytopenia,
initially 250 mg 2–3 times daily;
toxic epidermal necrolysis, urine darkens on
gradually increase at intervals of 2 or
standing, vomiting.
more days, if necessary; (maximum
dose, 3 g daily).
Drug Interactions:
Monitor closely with:
Dose Adjustments:
Drugs that enhance the therapeutic effect of
Renal impairment: Start with a small dose or
Methyldopa:
adjust dosage frequency. May require
Antihypertensive effect: Chlorpromazine,
only the usual initial dose. For severe
Drugs that reduce blood pressure
impairment, refer the patient to a
Drugs that increase risk of adverse or toxic
specialist.
effects of Methyldopa:
Chlorpromazine (extrapyramidal effects),
Precautions:
Salbutamol (acute hypotension)
Avoid abrupt withdrawal; monitor blood count
and liver function before treatment and at

Page | 99
CARDIOVASCULAR SYSTEM
Avoid concomitant use with:
Drugs that reduce the therapeutic effect of
Methyldopa:
Ibuprofen (antagonizes antihypertensive
effect), Iron Preparations {e.g., Ferrous
Sulfate, Ferrous Gluconate [due to reduced
bioavailability] (antihypertensive effect)},
Oral Contraceptives (Estrogen antagonizes
antihypertensive effect)
TEST INTERACTION. Produces a positive
direct Coombs’ Test, interfering with blood
cross-matching.
Administration: May be taken with or without
food. Advise the patient to get up gradually
from sitting or lying to minimize this effect,
and to sit or lie down if the patient becomes
dizzy or light-headed.
Pregnancy Category: B
ATC Code: C02AB01 (levorotatory)
C02AB02 (racemic)
DIURETICS
LOW CEILING DIURETICS
HYDROCHLOROTHIAZIDE
Rx
Oral.: 12.5 and 25 mg tablet
A moderately-potent, thiazide diuretic whose
maximal antihypertensive effect is usually
observed at doses lower than those that
produce maximal diuretic effect. It acts by
blocking the reabsorption of sodium in the
distal convoluted tubules of the nephrons.
Indications: Management of mild hypertension
(alone), or in moderate or severe
Page | 100
hypertension (in combination with other
drugs); edema.
Contraindications: Severe renal impairment or
anuria; severe hepatic impairment;
hyponatremia; hypercalcemia; refractory
hypokalemia; symptomatic
hyperuricemia; Addison disease.
Dose:
Hypertension, by mouth, ADULT, 12.5–25 mg
daily, increase to 25–100 mg daily if
necessary; CHILD, refer to a specialist.
Dose Adjustments:
Renal impairment: Avoid use if creatinine
clearance <10 mL/minute
Precautions:
High doses (may cause hypokalemia; avoid use
if there is a history of kidney stones).
Hypokalemia (may precipitate coma).
Gout (diuretic-induced rise in serum uric acid
concentration).
Heart failure with significant edema
(hyponatremia may occur).
Hepatic impairment (may precipitate hepatic
coma or encephalopathy).
Alcoholic cirrhosis (increased risk of
hypomagnesemia).
Renal impairment (may aggravate diabetes
mellitus, gout, and systemic lupus
erythematosus); porphyria.
Elderly (more susceptible to electrolyte
imbalance and orthostatic hypotension).
Pregnancy (avoid use; may cause electrolyte
disturbances and thrombocytopenia in
neonates if used during the third
trimester; reduction of maternal blood
volume may diminish uteroplacental
perfusion);
Lactation (may inhibit lactation).
Adverse Drug Reactions:
Common: Dizziness, headache, hyperuricemia,
hypochloremic alkalosis, hypokalemia,
hypomagnesemia, hyponatremia, lethargy,
muscle cramps, orthostatic hypotension,
polyuria, weakness
CARDIOVASCULAR SYSTEM
Less Common: Blurred vision, dyslipidemia,
hypercalcemia, hyperglycemia, impotence,
rash
Rare: Agranulocytosis, aplastic anemia,
cardiac arrhythmias, cholecystitis,
constipation, dermatitis, diarrhea, hemolytic
anemia, hypersensitivity reactions, impotence,
intrahepatic cholestatic jaundice, leukopenia,
nausea, necrotizing vasculitis, pancreatitis,
purpura, thrombocytopenia, toxic epidermal
necrolysis, visual disturbances, vomiting
Drug Interactions:
Monitor closely with:
Drugs that enhance the therapeutic effect of
Hydrochlorothiazide:
Drugs that reduce blood pressure
(additive hypotensive effects), Loop
Diuretics (synergistic effect; profound
diuresis and serious electrolyte
disturbance)
Drugs that increase the risk of adverse or toxic
effects of Hydrochlorothiazide:
Digoxin (cardiac toxicity due to
hypokalemia), Potassium lowering Drugs
(hypokalemia), Salbutamol (hypokalemia
with high doses)
Avoid concomitant use with:
Drugs that increase the risk of adverse or toxic
effects of Hydrochlorothiazide:
ACE Inhibitors (severe hypotension with
the first ACEi dose), Angiotensin II
Receptor Blockers (excessive
hypotension with the first ARB dose due
to volume depletion), Hydrocortisone
(hypokalemia), Ibuprofen (nephrotoxicity),
NSAIDs including Selective COX-2
Inhibitors (nephrotoxicity)
Drugs that reduce the therapeutic effect of
Hydrochlorothiazide: Hydrocortisone
(antagonism of diuretic effect), Ibuprofen
(antagonism of diuretic effect), NSAIDs
including Selective COX-2 Inhibitors (renal
function; diuretic and antihypertensive
effect), Lidocaine, Metformin (antagonism
of hypoglycemic effect), Oral
Contraceptives (antagonism of
antihypertensive effect)
Administration:
Usually taken once daily in the morning. If the
patient is to take it twice a day, take the first
dose in the morning and the second dose
before 6 in the evening.
Pregnancy Category: B
ATC Code: C03AA03
HIGH CEILING DIURETICS
FUROSEMIDE
Rx
Oral: 40 mg tablet
Inj.: 10 mg/mL, 2 mL ampule (IM, IV)
A potent, high-ceiling, sulfonamide loop
diuretic, which produces dose-dependent
diuresis of relatively short duration.
Indications: Management of edema;
congestive heart failure
Contraindications: Severe fluid and sodium
depletion
Dose:
Edema, by mouth, ADULT, 40 mg daily in
divided doses, may be increased
gradually to 120 mg in resistant edema;
CHILD, 1–3 mg/kg daily (maximum, 40
mg daily); INFANT, 1–6 mg/kg daily given
in divided doses every 6– 12 hours;
NEONATES or PREMATURE INFANTS, 1–4
mg/kg per dose once or twice daily due to
poor bioavailability.
Heart failure, by mouth, ADULT, initially 20–40
mg; may repeat the same dose or
increase dose in increments of 20–40 mg
per dose at intervals of 6–8 hours
(maximum total daily dose, 600 mg);
usual maintenance dose interval is once
Page | 101
CARDIOVASCULAR SYSTEM
or twice daily; adjust dosing frequency
based on patient-specific needs; CHILD
and INFANT, initially 2 mg/kg per dose,
increased in increments of 1– 2 mg/kg
per dose at intervals of 6–8 hours until a
satisfactory response is achieved
(maximum dose, 6 mg/kg per dose);
by IM or IV injection, ADULT, initially 20–40
mg per dose, may repeat the same dose
or increase dose in increments of 20 mg
per dose and administer 1–2 hours after
the previous dose (maximum dose, 200
mg per dose); given once or twice daily.
CHILD and INFANT, initially 1 mg/kg per
dose, may increase the dose in
increments of 1 mg/kg per dose and
administer not sooner than 2 hours after
the previous dose until a satisfactory
response is achieved; may administer
maintenance dose at intervals of every 6–
12 hours (maximum dose, 6 mg/kg per
dose);
by continuous IV infusion, ADULT, initially
administer an IV bolus dose 40–100 mg
over 1 to 2 minutes, followed by a
continuous IV infusion rate of 10–40
mg/hour; repeat loading dose before
increasing infusion rate
Dose Adjustments:
Renal impairment: In acute renal failure,
higher doses may be required to initiate
the desired response. Avoid use in
oliguric states. Not removed by
hemodialysis or peritoneal dialysis. A
supplemental dose is not necessary. In
CrCl <25 mL/min, use the upper end of
the initial infusion dosage range. If
urine output is <1 mL/kg per hour,
double as necessary to a maximum of
80–160 mg/hour. Monitor effects,
particularly with high doses
Geriatric: Reduce dose.
NOTE: Dose equivalency for patients with
normal renal function (approximate):
Furosemide 40 mg = Bumetanide 1 mg
= Torsemide 20 mg = Ethacrynic Acid
50 mg
Page | 102
Precautions:
WARNING: Cases of tinnitus, hearing
impairment, and deafness have been
reported. Ototoxicity is related to rapid
injection, severe renal impairment, use of
higher than recommended doses,
hyponatremia, or concomitant therapy with
aminoglycoside antibiotics or other ototoxic
drugs. If high doses are necessary,
parenteral therapy with controlled IV
infusion is advisable.
Prostatic enlargement and/or obstruction (may
precipitate acute urinary retention). Gout
(may be aggravated by diuretic-induced
hyperuricemia).
Hypotension. Diabetes (may see changes in
glucose control);
SLE (may cause SLE exacerbation or
activation).
Oliguria (correct hypovolemia before
administration)
Renal impairment (monitor electrolytes
particularly potassium and sodium, as
well as creatinine).
Hepatic impairment (hypokalemia may
precipitate coma); cirrhosis (diminished
natriuretic effect with increased
sensitivity to hypokalemia and volume
depletion); alcoholic cirrhosis (increased
risk of hypomagnesemia).
Severe urinary retention. Patients at high risk
for radiocontrast nephropathy (can lead to
a higher incidence of deterioration in
renal function).
Elderly (more susceptible to electrolyte
imbalance and orthostatic hypotension).
Pregnancy (avoid use; may cause electrolyte
disturbance in the fetus; possible
neonatal thrombocytopenia; monitor fetal
growth because of potential for higher
fetal birth weights); lactation (enters
breastmilk; use with caution).
Adverse Drug Reactions:
Common: Dehydration, dizziness, gout,
hyperuricemia, hypokalemia,
hypomagnesemia, hyponatremia, orthostatic
 CARDIOVASCULAR SYSTEM
hypotension, syncope Lidocaine (antagonized by hypokalemia),
Less Common: Dyslipidemia, hyperglycemia, Metformin (antagonism of hypoglycemic
hypocalcemia, concentration, rash effect) the therapeutic effect of these drugs
Rare: Acute pancreatitis, agranulocytosis, may be reduced.
bone marrow depression, bullous eruptions,
exfoliative dermatitis, hemolytic anemia, Administration: For oral administration, take a
interstitial nephritis. jaundice, photosensitivity, tablet once daily, in the morning. If to be
Stevens-Johnson syndrome, taken twice daily, take the first dose in the
thrombocytopenia, tinnitus, vertigo morning and the second dose at lunchtime.
Advise the patient to get up gradually from
Drug Interactions: sitting or lying to minimize dizziness upon
Monitor closely with: standing when taking the medicine. The
Drugs that enhance the therapeutic effect of patient should sit or lie down if dizziness
Furosemide: occurs
Alcohol (antihypertensive effect), Thiazide
Diuretics [e.g., Hydrochlorothiazide For IV administration, administer no faster
(profound diuresis; serious electrolyte than 4 mg/minute to avoid ototoxicity. Dilute
disturbance)] dose in a suitable amount of infusion fluid,
Drugs that increase risk of adverse or toxic according to the hydration of the patient.
effects of Furosemide:
Salbutamol (hypokalemia) Pregnancy Category: C
ACE Inhibitors [e.g., Enalapril (severe
hypotension with the first ACEi dose; ACEi- ATC Code: C03CA01
induced renal impairment)], ARBs
(excessive hypotension with the first ARB
dose due to volume depletion), Drugs
causing hypotension [e.g., Amlodipine,
Diazepam, Hydrochloro- thiazide,
LIPID MODIFYING AGENTS
Methyldopa (hypotension)], Digoxin (cardiac
toxicity due to hypokalemia), NSAIDs
HMG CoA REDUCTASE INHIBITORS
including COX-2 Inhibitors (nephrotoxicity),
Ototoxic Drugs [e.g., Gentamicin,
Streptomycin (ototoxicity)] - risk of adverse
ATORVASTATIN
or toxic effects may be increased Rx
Selective and non-selective NSAIDs - Reduce the
therapeutic effect of Furosemide:
Oral: 10 mg, 20 mg, 40 mg, and 80 mg tablet
Avoid concomitant use with: (as calcium)
Hydrocortisone (hypokalemia) Increases risk of
adverse or toxic effects of Ibuprofen A selective, competitive inhibitor of 3-hydroxy-
(nephrotoxicity) - 3-methylglutaryl coenzyme A (HMG-CoA)
Increase risk of adverse or toxic effects of reductase, which prevents the conversion
Furosemide of HMG-CoA to mevalonate, an early and
Hydrocortisone (antagonism of diuretic effect), rate-limiting step in cholesterol
Ibuprofen (antagonism of diuretic effect), biosynthesis.
Oral Contraceptives (Estrogen antagonizes
diuretic effect) - Reduce the therapeutic Indications: Adjunct to diet for the reduction of
effect of Furosemide elevated total cholesterol, LDL

Page | 103
CARDIOVASCULAR SYSTEM
cholesterol, apolipoprotein B, and
triglycerides, and elevation HDL
cholesterol in patients with primary
hypercholesterolemia and combined
hyperlipidemia
NOTE: Atorvastatin has not been studied in
conditions where the major lipoprotein
abnormality is the elevation of
chylomicrons (Fredrickson Types I and V).
Contraindications: Active liver disease,
including unexplained persistent
elevations in hepatic transaminase levels;
pregnancy; breastfeeding
Dose:
NOTE: Individualize starting and maintenance
doses according to patient characteristics,
such as the goal of therapy and response.
Hyperlipidemia, by mouth, ADULT, initially 10
or 20 mg once daily; usual range, 10–80 mg
once daily; patients who require an LDL-C
reduction of more than 45% may be started
at 40 mg once daily.
Heterozygous Familial Hypercholesterolemia,
by mouth, CHILD 10–17 years, initially 10
mg daily (maximum dose, 20 mg daily);
adjust doses at intervals of 4 weeks or more.
Homozygous Familial Hypercholesterolemia,
by mouth, ADULT, 10–80 mg daily.
Dose Adjustments:
Renal impairment: Hemodialysis does not have
any significant effect on atorvastatin
clearance.
Hepatic impairment: In patients with active
liver disease, use is contraindicated.
Precautions:
Skeletal muscle effects (rare cases of
rhabdomyolysis with acute renal failure
secondary to myoglobinuria have been
reported; immune-mediated necrotizing
myopathy or IMNM rarely occurs).
Liver dysfunction (jaundice has been reported;
reversible increases in liver function tests
may occur); hepatic impairment;
Page | 104
endocrine function (increased HbA1c and
fasting serum glucose levels have been
reported).
CNS toxicity (brain hemorrhage and CNS
vascular lesions, characterized by
perivascular hemorrhages, edema, and
mononuclear cell infiltration of
perivascular spaces have been observed
in animal studies); stroke or TIA (may
occur).
Elderly (use with caution; age>65 is a
predisposing factor for myopathy);
children (use of doses >20 mg has not
been studied).
Pregnancy (crosses the placenta; use with
caution; insufficient studies on use during
pregnancy); lactation (not known if
excreted in breastmilk; use with caution).
Adverse Drug Reactions:
Common: Nasopharyngitis, arthralgia,
diarrhea, pain in extremity, urinary tract
infection, dyspepsia, nausea, musculoskeletal
pain, muscle spasms, myalgia, insomnia,
pharyngolaryngeal pain
Less Common and rare: Rhabdomyolysis,
myopathy, liver enzyme abnormalities,
malaise, pyrexia, abdominal discomfort,
eructation, flatulence, hepatitis, cholestasis,
muscle fatigue, neck pain, joint swelling,
hyperglycemia, nightmare, epistaxis, urticaria,
vision blurred, tinnitus, positive WBC in urine,
anaphylaxis, angioneurotic edema, bullous
rashes, fatigue, tendon rupture, fatal and non-
fatal hepatic failure, dizziness, depression,
peripheral neuropathy, pancreatitis
Drug Interactions:
Monitor closely with:
Oral Contraceptives [norethindrone; ethinyl
estradiol] - Increased distribution of these
drugs may occur.
Avoid concomitant use with:
Cyclosporine - Increases distribution of
Atorvastatin
CARDIOVASCULAR SYSTEM
Colchicine (including rhabdomyolysis),
Cyclosporine, CYP3A4 Inhibitors, i.e.,
Clarithromycin, HIV Protease Inhibitors,
Itraconazole, Fibric Acid Derivatives,
Niacin –
Increase risk of adverse or toxic effects
(myopathy) of Atorvastatin:
CYP3A4 Inhibitors (Strong) i.e., Clarithromycin,
HIV Protease Inhibitors, Itraconazole,
Grapefruit Juice [avoid excessive
consumption, i.e.,>1.2 L/day] - Increase
serum concentration of Atorvastatin:
Administration: Administer as a single dose at
any time of the day, with or without food.
Pregnancy Category: X
ATC Code: C10AA05
ROSUVASTATIN
Rx
Oral: 10 mg and 20 mg tablet (as calcium
salt)
An active HMG-CoA reductase inhibitor, which
is effective in reducing LDL-cholesterol
concentration and has been efficacious
in severe hypercholesterolemia.
Indications: Prevention of cardiovascular
events in patients at high risk of a first
cardiovascular event; mixed dyslipidemia,
or homozygous familial
hypercholesterolemia in patients who
have not responded adequately to diet
and other appropriate measures; (adults)
treatment of primary
hypercholesterolemia, e.g., heterozygous
familial and non-familial
hypercholesterolemia; (children and
adolescents) treatment of heterozygous
familial hypercholesterolemia
Contraindications: Pregnancy; breastfeeding;
women who are planning to conceive or
those using inadequate contraception;
severe renal impairment; active liver
disease; unexplained persistent elevation
in serum transaminases
Dose:
NOTE: Individualize doses based on baseline
LDL cholesterol levels, recommended goal
of therapy, and patient response. Adjust
doses at 4-week intervals or more.
Reserve the highest dose (40 mg) only for
patients who fail to achieve desired
cholesterol level at 20 mg daily.
High cardiovascular risk, by mouth, ADULT
MEN >50 years and WOMEN >60 years
20 mg once daily
Hypercholesterolemia, by mouth, ADULT,
initially 5 or 10 mg once daily, may
increase the dose to 20 mg if necessary
at intervals of at least 4 weeks; usual
range, 5–20 mg once daily (maximum
dose, 40 mg once daily); CHILD 10–18
years, initially 5 mg once daily (maximum
dose, 20 mg once daily).
Dose Adjustments:
Geriatric: Start at a low dose. Initiate dose at 5
mg once daily.
Renal impairment: For mild-to-moderate
impairment, initiate dose at 5 mg once
daily with a maximum dose of 10 mg
once daily.
Asian ancestry: Patients may build up higher
drug levels and be at higher risk to
develop myopathy. Initiate dose at 5
mg. Do not administer 40 mg dose.
Patients at risk for myopathy: Consider lower
initial dose, e.g., 5 mg daily in adults.
Precautions:
Renal impairment (may reduce the elimination
of rosuvastatin; increases risk of
myopathy);
Hepatic effects (hepatic impairment may
impair elimination of rosuvastatin).
Page | 105
CARDIOVASCULAR SYSTEM
Myopathy (may occur with lipid-lowering agent; Warfarin - therapeutic effect may be enhanced.
monitor creatine kinase (CK) levels and (increased INR)
discontinue if these are markedly
elevated; increased risk for Niacin (rhabdomyolysis) - increased toxicity
rhabdomyolysis); immune-mediated due to pharmacodynamic synergism
necrotizing myopathy (have been rarely Warfarin (bleeding) – increased risk for toxic
reported) effects
Severe intercurrent illness, e.g., infection,
trauma, metabolic disorder, endocrine Bile Acid Binding Resins - Reduces absorption
and electrolyte disturbances, of Rosuvastatin: [administer statin at least 1
uncontrolled seizures (increases risk of hour before, or 4 hours after, the resin]
myopathy, rhabdomyolysis, and renal
failure). Administration: May be taken with or without
Diabetes mellitus (small increases in HbA1c food. May be taken at any time of the day.
and fasting blood glucose have been
Pregnancy Category: X
reported); hematuria and proteinuria;
hypothyroidism (should be managed
ATC Code: C10AA07
adequately before starting treatment with
a statin) Treatment with systemic
Sodium Fusidate (may increase the risk of
rhabdomyolysis)
SIMVASTATIN
Elderly (risk of myopathy is higher); children Rx
(safety and efficacy have not been
established in children
Oral: 20 mg and 40 mg tablet
Adverse Drug Reactions:
Common: Abdominal pain, arthralgia, An HMG-CoA reductase inhibitor, which is
constipation, diabetes mellitus, dizziness, effective in reducing LDL cholesterol
headache, flu-like illness, insomnia, mild GI concentration, and has been reported to
symptoms, myalgia, nausea, UTI, weakness reduce the incidence of fatal and non-
Less Common: Pruritus, rash, urticaria fatal MI, stroke and mortality, and the
Rare: Myopathy (including myositis), need for coronary and non-coronary
angioedema, alopecia, amnesia, anaphylaxis, revascularization procedures.
gynecomastia, hematuria, hepatitis,
hypersensitivity (rash, pruritus, urticaria), Indications: For prevention of cardiovascular
impotence, interstitial lung disease, jaundice, events in patients with high
liver failure, pancreatitis, paresthesia, cardiovascular risk due to atherosclerotic
peripheral neuropathy, proteinuria, cardiovascular disease or DM; primary
rhabdomyolysis, renal failure, toxic epidermal hypercholesterolemia; homozygous
necrolysis familial hypercholesterolemia, or
combined hyperlipidemia in patients who
Drug Interactions: have not yet responded adequately to diet
Monitor closely with: or other appropriate measures; (children
Fibrates e.g., Fenofibrate (myopathy; and adolescents) heterozygous familial
rhabdomyolysis) -Enhance the therapeutic hypercholesterolemia
effect of Rosuvastatin
Contraindications: Known hypersensitivity to
Avoid concomitant use with: simvastatin or any component of the

Page | 106
CARDIOVASCULAR SYSTEM
formulation; active liver disease, or
persistently abnormal liver function tests;
porphyria; pregnancy (congenital
anomalies reported; decreased synthesis
of cholesterol possibly affects fetal
development); breastfeeding
Dose:
Homozygous familial hypercholesterolemia, by
mouth, ADULT, initially 40 mg daily at night,
adjusted at intervals of at least 4 weeks (see
restricted dosing with 80 mg once daily at
night).
Prevention of cardiovascular events, by mouth,
ADULT, initially 10–40 mg once daily at
night, adjusted at intervals of at least 4
weeks with the recommended starting dose
of 40 mg for those at high risk of
cardiovascular events.
Primary hypercholesterolemia or combined
hyperlipidemia, by mouth, ADULT, 10–20
mg daily at night, adjusted at intervals of at
least 4 weeks (see restricted dosing with 80
mg once daily at night).
Heterozygous familial hypercholesterolemia,
by mouth, ADOLESCENT 10–18 years,
initially 10 mg at night, may increase if
necessary, at intervals of at least 4 weeks to
a maximum of 40 mg at night.
NOTE: Maximum simvastatin dose:
concomitant with verapamil and diltiazem,
10 mg daily; with concomitant amiodarone
or amlodipine, 20 mg daily. Contraindicated
with erythromycin, clarithromycin,
ketoconazole, HIV protease inhibitors, and
gemfibrozil.
Dose Adjustments:
Geriatric: Use with caution. Start at a low dose
Renal impairment: For mild-to-moderate renal
impairment, dose reduction is
warranted. For severe impairment,
refer the patient to a specialist.
Hepatic impairment: Use with caution. Start at
a low dose. Contraindicated in active
liver disease or persistent abnormal
liver function tests.
Restricted dosing for 80 mg: Use with caution.
Start at a low dose. Contraindicated in
active liver disease or persistent
abnormal liver function tests; Monitor
for myopathy.
Precautions:
Muscle effects (do not start simvastatin if
creatine kinase is elevated in patients at
high risk of muscle effects; risk of
myopathy is increased if simvastatin is
given at high doses or with a fibrate, with
lipid-lowering doses of nicotinic acid, or
with immunosuppressants; monitor liver
function and creatine kinase).
Rhabdomyolysis (rarely occurs; the risk
may be increased in renal impairment and
hypothyroidism).
Severe intercurrent illness, e.g., infection,
trauma, or metabolic disorder (increased
risk of myopathy, rhabdomyolysis, and
renal failure;); hypothyroidism (should be
managed before starting treatment with a
statin); surgery (increased risk of acute
renal impairment, which increases the
likelihood of myopathy and
rhabdomyolysis).
History of liver disease, or high alcohol intake
(monitor liver function at initiation of
treatment, after 4 to 12 weeks and
periodically thereafter, e.g., at 6-month
intervals or when clinically indicated;
discontinue if serum transaminase
concentration rises to, and persists at, 3
times the upper limit of the reference
range); renal impairment).
Elderly (increased risk of myopathy); Children
(safety and efficacy have not been
established in children <10 years)
Adverse Drug Reactions:
Common: Abdominal pain, atrial fibrillation,
constipation, diabetes mellitus, dizziness,
eczema, edema, elevated CK and serum
transaminase level, flatulence, gastritis,
headache, insomnia, myalgia, nausea, upper
respiratory infection, urinary tract infection,
vertigo, vomiting
Less Common: Mild GI symptoms
Rare: Anaphylaxis, anemia, angioedema,
gynecomastia, hepatitis, hypersensitivity,
Page | 107
CARDIOVASCULAR SYSTEM
impotence, interstitial lung disease, jaundice,
liver failure, myopathy, pancreatitis, peripheral
neuropathy, pruritus, rash, renal failure,
rhabdomyolysis, toxic epidermal necrolysis
Drug Interactions:
Monitor closely with:
Carbamazepine- Reduces the therapeutic
effect of Simvastatin
Avoid concomitant use with:
Clotrimazole (myopathy), CYP3A4 Inhibitors,
e.g., Clarithromycin, Erythromycin,
Ketoconazole, Diltiazem (myopathy;
rhabdomyolysis)- Increase the risk of
adverse or toxic effects of simvastatin
CYP3A4 Inhibitors, e.g., Clarithromycin,
Erythromycin, Ketoconazole, Diltiazem -
Increase the risk of adverse or toxic
effects of simvastatin
Bile Acid Binding Resins - Reduce absorption of
simvastatin: [administer statin at least 1
hour before, or 4 hours after, the resin]
Administration: May be taken with or without
food. Avoid excessive consumption, i.e., >1 L
daily of grapefruit juice.
Pregnancy Category: X
ATC Code: C10AA01
FIBRATE
FENOFIBRATE
Rx
Oral: 200 mg capsule
160 mg and 200 mg tablet
A peroxisome proliferator receptor alpha
(PPARα) activator, which modulates
lipoprotein synthesis and catabolism. It
reduces plasma triglyceride, moderately
increases high-density lipoprotein (HDL),
Page | 108
and has a variable effect on LDL
concentrations.
Indications: Hypertriglyceridemia; dyslipidemia
associated with type 2 diabetes; second-line
treatment in hypercholesterolemia
Contraindications: Photosensitivity to
ketoprofen; pancreatitis, unless due to
hypertriglyceridemia; severe renal
impairment, including patients receiving
dialysis; hepatic impairment; primary biliary
cirrhosis; gallstones; gall bladder disease;
unexplained, persistent liver function
abnormality; pregnancy; lactation
Dose:
NOTE: At least 2-3 months of therapy is
required to determine efficacy.
Hyperlipidemias, by mouth, ADULT, 200–300
mg once daily in divided doses; usual range,
200–400 mg daily; CHILD >10 years old, up
to a maximum of 5 mg/kg daily.
Dose Adjustments:
Geriatric: Use with caution. May need dose
adjustment.
Renal Impairment: For mild-to-moderate
impairment, dose reduction is
warranted. Initiate dose at 40–50 mg
once daily in adults. Refer the child to a
pediatrician. For severe impairment,
fenofibrate is contraindicated.
Precautions:
NOTE: Fenofibrate has a uricosuric effect,
which may reduce uric acid
concentrations by about 25%.
Hyperlipidemia; myopathy, myositis, and
rhabdomyolysis (have been reported;
concomitant HMG-CoA reductase inhibitor
may potentiate rhabdomyolysis and lead
to acute renal failure).
Increase in hepatic transaminases (monitor
regularly and discontinue if enzyme levels
persist 3 times above the upper limit of
normal); increase in serum creatinine
(may occur; monitor renal function).
CARDIOVASCULAR SYSTEM
Avoid exposure of skin to sun, wear protective Administration: Best taken with food as food
clothing and use sunscreen increases the bioavailability of
Lack of optimal response (withdraw therapy if fenofibrate.
an adequate response is not obtained
after 2–3 months of therapy at the Pregnancy Category: C
maximal daily dose).
Women and obese individuals (at high risk for ATC Code: C10AB05
biliary tract disease; modest increase in
the risk of cholesterol gallstones,
reflecting an increase in the cholesterol
content of bile; may cause cholelithiasis)
ANTITHROMBOTIC DRUGS
Patients at risk for venous thromboembolism
(associated with pulmonary embolism
PLATELET AGGREGATION INHIBITORS
and deep venous thrombosis).
Elderly (higher incident of renal impairment)
Pregnancy (embryotoxicity in animal studies);
ASPIRIN
lactation.
Rx
Adverse Drug Reactions:
Common: Arthralgia, bronchitis, cough, Oral: 80 mg and 100 mg tablet
dizziness, fatigue, headache, insomnia, GI
disturbances (e.g., dyspepsia, abdominal An irreversible, cyclooxygenase (COX) inhibitor,
pain); hypertension, nausea, rhinitis, infections which inhibits platelet aggregation, and is
(e.g., urinary tract, respiratory tract) useful in the long-term management of MI,
Less Common: Pancreatitis, photosensitivity, including the prevention of further attacks.
pulmonary embolism, VTE
Rare: Agranulocytosis, anemia, arrhythmias, Indications: Primary prevention of acute MI
hepatitis, cholestatic jaundice, gallstones, and stroke in patients with risk factors;
hypersensitivity reactions (e.g., angioedema, secondary prevention of thrombotic
anaphylaxis, exfoliative dermatitis), cardiovascular or cerebrovascular
hypokalemia, leukopenia, myopathy, disease, and following bypass surgery;
rhabdomyolysis, thrombocytopenia acute MI; acute ischemic stroke.

Drug Interactions: Contraindications: Known hypersensitivity

Monitor closely with: (including asthma, angioedema,
Insulins, Sulfonylureas e.g. Gliclazide urticaria, and rhinitis) to acetylsalicylic
(hypoglycemic effect) - Enhance the acid and any other NSAIDs, or any
therapeutic effect of the following drugs: component of the formulation; children
Atorvastatin - Increases risk of adverse or toxic and adolescents
effects of Statins (myopathy;
rhabdomyolysis) Dose:
Prophylaxis of myocardial infarction or
Avoid concomitant use with: cerebrovascular disease, by mouth,
Warfarin - Enhances therapeutic effect of ADULT, 80-100 mg once daily.
Anticoagulants (anticoagulant effect) Treatment of acute MI, by mouth, ADULT, 150-
Anticoagulants, e.g., Warfarin - Increases risk 300 mg once daily.
of adverse or toxic effects (e.g., bleeding)
Bile Acid Sequestrants - Reduces absorption of
Fenofibrate:
Page | 109
CARDIOVASCULAR SYSTEM
NOTE: See under Platelet Aggregation Acute coronary syndrome: ST-segment
Inhibitors in Blood and Blood Forming elevation MI (STEMI), by mouth, ADULT,
Organs for other important therapeutic 75 mg/day (in combination with aspirin
information. 162-325 mg/ day, and then 81-162
mg/day).
Coronary artery disease, by mouth, ADULT, 75
mg once daily.
CLOPIDOGREL Recent MI, stroke or established peripheral
Rx arterial disease, by mouth, ADULT, 75
mg/day.

Oral: 75 mg tablet NOTE: See under Platelet Aggregation

Inhibitors in Blood and Blood Forming
A thienopyridine-derived, platelet aggregation
Organs for other important therapeutic
inhibitor that has no effect on information,
prostaglandin metabolism unlike aspirin,
and is used as an alternative for patients
who are contraindicated to aspirin in the
treatment of thrombosis.

Indications: Prevention of atherothrombotic

events in peripheral arterial disease, MI,
or ischemic stroke; in acute coronary
syndrome without ST-segment elevation
(unstable angina or non-Q wave MI),
including patients undergoing stent
placement following percutaneous
coronary intervention (in combination with
aspirin); in acute MI with ST-segment
elevation, and in combination with ASA in
medically treated patients eligible for
thrombolytic therapy; in patients with
atrial fibrillation, and for whom oral
anticoagulation is unsuitable.

Contraindications: Known hypersensitivity to

clopidogrel or any component of the
formulation; severe liver impairment;
intracranial hemorrhage, peptic ulcer, or
other pathological bleeding;
breastfeeding.

Dose:
Acute coronary syndrome: unstable angina,
non-ST-segment elevation MI (NSTEMI),
by mouth, ADULT, 300 mg loading
dose; then 75 mg/day in combination
with aspirin 75-100 mg/day.

Page | 110
DERMATOLOGICALS
Requires a longer duration of treatment, about
DERMATOLOGICALS 7 days, to clear the infection. Avoid oral
antifungals.

Precautions:
ANTIFUNGALS FOR
Discontinue if irritation or sensitivity occurs;
DERMATOLOGICAL USE Damages latex condoms and diaphragms;
Pregnancy (safety in the first trimester has
ANTIFUNGALS FOR TOPICAL USE not been established)

Adverse Drug Reactions:

Imidazole and Triazole Derivatives
Common: Local pain or discomfort
Less Common: Blistering, burning, edema,
erythema, general skin irritation, itch, peeling,
CLOTRIMAZOLE
Rx pruritus, stinging
Rare: Allergic reactions

Cream: 1% (10 mg/ g), 3 g, 10 g and 20 g Drug Interactions:

aluminum collapsible tube Monitor closely with:
2% (20 mg/ g), 30 g aluminum Simvastatin – with increased risk of adverse or
collapsible tube toxic effect (myopathy)

A broad-spectrum imidazole active against Administration: For topical application, gently

fungi, (both dermatophytes and yeasts) and
gram-positive cocci (Staphylococcus and
Streptococcus spp.)
Indications: Ringworm; skin infections,
including pityriasis versicolor and
dermatophytosis (e.g., tinea corporis, tinea
pedis, tinea cruris); protozoal infections (e.g.
trichomoniasis)
Contraindications: Severe liver impairment
massage a sufficient amount into the
affected and surrounding skin areas
twice daily, in the morning and evening.
If the feet are infected, wash and dry
feet, especially between the toes,
before applying the cream.
Pregnancy Category: B
ATC Code: D01AC01

Dose:
Anogenital candidiasis, by topical application, KETOCONAZOLE
ADULT, apply 1% cream to anogenital area Rx
2–3 times daily.
Skin infections, including pityriasis versicolor
Shampoo: 2% (20mg/g) 6 mL foil sachet, 10
and dermatophytosis, by topical application,
mL, 60 mL, and 100 mL bottle
ADULT, apply cream 2– 3 times daily for 1–
2 weeks.
Imidazole derivate that exerts its antifungal
effects by altering the permeability of the cell
Dose Adjustments:
wall by blocking fungal cytochrome P450.
Vulvovaginal candidiasis in pregnancy:
This inhibits the biosynthesis of triglycerides
and phospholipids in the fungal cell,

Page | 111
DERMATOLOGICALS
inhibiting several fungal enzymes that result Pregnancy Category: C
in a build-up of toxic concentrations of
hydrogen peroxide. ATC Code: D01AC0

Indications: Treatment of tinea corporis, tinea

cruris, tinea pedis, tinea versicolor,
cutaneous candidiasis, seborrheic ANTIPRURITICS, INCLUDING
dermatitis, pityriasis capitis; treatment and ANTIHISTAMINES,
prophylaxis of pityriasis versicolor ANESTHETICS, ETC.
Dose:
As shampoo, massage onto scalp. Leave on
for 3-5 minutes then rinse.
OTC CALAMINE, PLAIN
Seborrheic dermatitis and pityriasis capitis,
treatment, apply shampoo twice weekly for
2-4 weeks Lotion: 8%, 60 mL and 120 mL bottle
Seborrheic dermatitis and pityriasis capitis,
pro- phylaxis, apply shampoo once every 1 A topical antipruritic substance, which contains
or 2 weeks basic zinc oxide with about 0.5% colored
ferric oxide.
Indications: Symptomatic treatment of mild
Dose Adjustment: No information was found pruritus and insect stings

Precautions: Hypersensitivity reactions; Contraindications: Avoid application before x-

Irritation; Lactation (do not apply to the
breast area of breastfeeding mothers).
Adverse Drug Reactions:
Common: Stinging, local burning, acne,
allergic reaction, contact dermatitis,
discharge, dizziness, dryness, erythema,
facial swelling, headache, impetigo,
keratoconjunctivitis sicca, nail
discoloration, ocular irritation or swelling,
pain, paresthesia, pruritus, pustules,
pyogenic granuloma, severe irritation
ray (zinc oxide may affect outcomes)
Dose:
Mild pruritus, ADULT and CHILD, apply liberally
to the entire affected area 3–4 times daily,
or as often as needed.
Precautions:
If the condition worsens or if rash develops,
stop the medication immediately.
Adverse Drug Reactions:
Rare: Irritation, rash

Drug Interactions: No known significant Drug Interactions:

interactions
Administration: For external use only. Do NOT
administer intravaginally.
Do NOT apply directly to hands. Do NOT apply
to the eyes. If contact with eyes, mouth,
or vagina occurs, rinse the exposed areas
thoroughly with water.
Monitor closely with:
Simvastatin – with increased risk of adverse or
toxic effect (myopathy)
Administration: Shake well prior to use. Apply
gently with a pad of cotton wool to the
affected parts as required. Do NOT use on
open wounds or burns. Avoid contact with

Page | 112
DERMATOLOGICALS
the eyes and the mucous membranes of
the mouth, nose, and anogenital area. Adverse Drug Reactions:
Pregnancy Category: No information was Common: Rashes, irritation
found Less Common: Hypersensitivity reactions

ATC Code: Not available Drug Interactions:

Avoid concomitant use with:
Ciprofloxacin (antagonistic activity)
ANTIBIOTICS AND
CHEMOTHERAPEUTICS FOR Administration: For external use only. Observe
DERMATOLOGICAL USE caution when applying in the eye region;
may cause eye irritation.

ANTIBIOTICS FOR TOPICAL USE Pregnancy Category: Not available

ATC Code: D06AX01

FUSIDATE SODIUM
OTC
(FUSIDIC ACID) MUPIROCIN
Rx
Cream: 2%, 5g tube
Ointment: 2%, 15g tube
Cream: 2%, 5 g sachet and 15 g tube
Ointment: 2%, 5 g and 15 g tube
An antibiotic derived from Fusidium
coccineum, which is active against
A bacteriostatic that inhibits protein synthesis
several gram-positive organisms and can
of the bacteria by binding to isoleucyl
penetrate intact skin. It acts by disrupting
transfer RNA synthetase
the translocation of peptide subunits and
elongating the peptide chain of
Indications: Management of impetigo;
susceptible bacteria, inhibiting protein
secondary skin infections (up to 10 cm in
synthesis.
length or 100 cm2 in area) due to
susceptible Staphylococcus aureus and
Indications: Treatment of skin infections
Streptococcus pyogenes.
caused by staphylococci, streptococci,
and Corynebacterium minutissimum;
Dose:
impetigo; infected wounds; folliculitis;
Secondary skin infection, by topical
boils; sycosis barbae; carbuncles;
application, ADULT and CHILD ≥3 months,
hidradenitis; paronychia; erythrasma
as cream, apply to affected area 3 times
daily for up to 10 days; re-evaluate within 7
Dose:
days if no clinical response.
Skin infection, by topical application, ADULT,
Impetigo, by topical application, ADULT and
apply to the affected area 2–3 times daily
CHILD ≥2 months, as ointment, apply to
for 7 days; may be used with or without
affected area 3 times daily for up to 5–10
covering dressing.
days; re-evaluate after 3–5 days if no clinical
response.
Precautions:
Hepatic disease (monitor liver function);
Precautions:
Neonates; Lactation.

Page | 113
DERMATOLOGICALS
WARNING: Prolonged use may result in the desired, cover the treated area with a
overgrowth of nonsusceptible gauze dressing.
microorganisms, including fungi.
Do NOT apply concurrently with any other
Extensive burns and wounds; Renal lotions, creams, or ointments.
impairment; Local irritation (discontinue
use when sensitization or severe local Pregnancy Category: C
irritation occurs); Lactation (not known if
present in breastmilk, has effects on ATC Code: D06AX09
breastfed child and milk production).

Dose adjustment: CHEMOTHERAPEUTICS USE

Renal Impairment:
Use with caution. Some products contain
polyethylene glycol, which may be SILVER SULFIDIAZINE
absorbed from open wounds and Rx
damaged skin and secreted by the
kidneys.
Cream: 1%, 15 g, and 25 g tube
Adverse Drug Reactions: 500 g jar (micronized)
Common and Less Common: Burning, stinging,
pruritus, pain, rash, erythema, dry skin, A bactericidal agent with a broad spectrum of
tenderness, cellulitis, pain or bleeding activity against gram-negative and gram-
secondary to eczema, secondary wound positive bacterial, as well as yeast.
infection, urticaria, swelling, increased
exudates, contact dermatitis, Indications: Adjunct for the prevention and
furunculosis, exfoliative dermatitis treatment of wound sepsis in patients
Rare: Systemic reactions (e.g., nausea, with second and third-degree burns
headache, dizziness, abdominal pain,
Contraindications: Pregnancy approaching or
ulcerative stomatitis, systemic allergic
at term; Lactation; Premature infants;
reactions)
Newborns ≤2 months; Porphyria
Drug Interactions:
Dose:
Avoid concomitant use with:
Wound due to burns, by topical application,
Chloramphenicol - Reduces the therapeutic
ADULT, apply 1 to 2 times daily to a
effect of Mupirocin (interferes with the
thickness of approximately one-sixteenth
antibacterial action of Mupirocin in RNA
of an inch; reapply as needed.
synthesis)
Dose adjustment:
Administration: For external use only. NOT for
Renal Impairment:
intranasal, ophthalmic, or other mucosal
Use with caution. Some products contain
use.
polyethylene glycol, which may be
absorbed from open wounds and
Avoid contact with eyes. In case of accidental
damaged skin and secreted by the
contact, rinse well with water.
kidneys.
Apply a small amount to the affected area
using a cotton swab or gauze pad. If Precautions:

Page | 114
DERMATOLOGICALS
Maintain adequate fluid intake; Prolonged
application over a large area may result in CORTICOSTEROIDS,
argyria; Sulfonamides; G6PD deficiency; DERMATOLOGICAL
Renal and hepatic impairment; Children; PREPARATIONS
Lactation (use with caution).

Adverse Drug Reactions: CORTICOSTEROIDS

Common: Leukopenia, nausea, vomiting,
diarrhea, hypersensitivity, skin reactions,
hematuria, crystalluria, thrombocytopenia,
leucopenia, eosinophilia, Stevens-Johnson
syndrome (potentially fatal), agranulocytosis
(potentially fatal), jaundice (potentially fatal),
hepatitis (potentially fatal)
Less Common: Skin necrosis, erythema
multiforme, skin discoloration, burning
sensation, rashes, and interstitial nephritis
Rare: Skin rash
Drug Interactions:
No known significant interactions
Administration: For external use only.
Dressings may or may not be used.
Clean and debride burn wounds, then apply to
the affected area under sterile conditions.
Burn areas should always be well covered
by the cream.
Reapply immediately after hydrotherapy.
Continue treatment until satisfactory
healing has occurred or until the burn site
is ready for grafting.
Do NOT withdraw from the therapeutic regimen
while there remains the possibility of
infection except if a significant adverse
reaction occurs.
Pregnancy Category: B
ATC Code: D06BA01
GENERAL INFORMATION
Corticosteroids are a group of natural and
synthetic analogues of the hormones secreted
by the hypothalamic-anterior pituitary-
adrenocortical (HPA) axis. Corticosteroids are
classified as glucocorticoids,
mineralocorticoids, and corticotropins.
Glucocorticoids are potent anti-inflammatory
agents that affect glucose utilization, fat
metabolism, and bone development.
Mineralocorticoids control the retention of
sodium and water in the kidneys.
Corticotropins, also known as
adrenocorticotropic hormone (ACTH), control
the secretion of hormones by the pituitary
gland.
Precautions:
WARNING: NOT for use in children under 2
years of age.
NOT for diaper dermatitis, ocular herpes
simplex, cerebral malaria, fungal infections,
or viral hepatitis.
Application under occlusion may result in an
increased incidence of adverse effects.
Adrenal suppression; Anaphylactoid reactions;
contact dermatitis; Eczema; Irritation
(discontinue immediately); Skin infections
(use appropriate antifungal or
antibacterial agent; discontinue use until
the infection has been adequately
controlled); Fungal or bacterial
dermatologic infection (institute
appropriate antifungal or antibacterial
therapy; if the infection does not resolve

Page | 115
DERMATOLOGICALS
promptly, discontinue use until the Entire arm and hand 4 FTU
infection has been adequately
controlled); Immunosuppression (observe Entire leg and foot 8 FTU
closely patients with latent tuberculosis
and/or tuberculosis reactivity); Kaposi NOTE: Above measurements are approximated
sarcoma; Myopathy; Myasthenia gravis; on an average adult. Values may differ based
Psychiatric disturbances; Sensitization; on patient size.
Skin reactions (discontinue if skin
irritation or contact dermatitis occurs; do
not use in patients with decreased skin
circulation); Systemic effects; Diabetes
OTC HYDROCORTISONE
mellitus; Gastrointestinal disease;
Ulcerative colitis; Osteoporosis; Hepatic
impairment; Renal impairment;
Cardiovascular disease; Myocardial Topical: 1%, ointment or cream, 5 g tube
infarction; Ocular disease; Thyroid
disease (dose adjustment may be A topical corticosteroid having relatively mild
required); Stress due to trauma, surgery, anti-inflammatory potency that is applied
or severe infection (may require higher in short courses of 1-2 weeks to manage
doses); Some dosage forms may contain mild areas of contact and atopic
benzyl alcohol and/or sodium benzoate or dermatitis.
benzoic acid; Elderly; Children; Lactation
Indications: Contact dermatitis, atopic
dermatitis (eczema), lichen planus;
Drug Interactions:
pityriasis rosea; intractable pruritus and
Monitor closely with:
Corticorelin - Reduces therapeutic effect phototoxic reactions, including
polymorphic light eruptions and actinic
(plasma ACTH response)
prurigo; short-term treatment of psoriasis
Fingertip units (FTU) for Topical Steroids: of the face and flexures.
One FTU is the amount of topical steroid that is
Contraindications Known hypersensitivity to
squeezed out from a standard tube (5 mm
hydrocortisone or any component of the
nozzle) along an adult's fingertip, from the
formulation; rosacea; acne vulgaris;
very end of the finger to the first crease in
perioral dermatitis; untreated skin
the finger. Two FTUs are about the same
infections (bacterial, fungal, or viral skin
as 1 g of topical steroid. One FTU is
lesions); areas with impaired circulation;
enough to treat an area of skin twice the
broken skin.
size of an adult's hand which is flattened
with the fingers together.
Dose:
Inflammatory skin conditions, by topical
Area of skin to be FTU per application, ADULT and CHILD, apply
treated (average dose
sparingly to the affected area, 1 to 2 times
adult)
daily until improvement occurs, then less
Hand and fingers 1 FTU
(front and back) frequently.
Front of chest and 7 FTU
abdomen Precautions:
Back and buttocks 7 FTU WARNING: Topical steroids may be
systematically absorbed to some degree
Face and neck 2.5 FTU

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DERMATOLOGICALS
and chronic use may cause some of the
problems associated with systemic steroids.
Diabetes (avoid extensive use as systemic
absorption can increase blood glucose
concentration); immunocompromised
patients (can lead to further
immunosuppression when used
extensively); concomitant use with
occlusive dressings (may increase
penetration into keratinized lesions).
Children (avoid prolonged use; increased
systemic absorption due to higher surface
area–weight ratio); secondary infection
requires treatment with an appropriate
antimicrobial agent.
Pregnancy (use the lowest appropriate potency
for the shortest time necessary);
breastfeeding (ensure that the breast
area is free from corticosteroid before
breastfeeding).
Adverse Drug Reactions:
Common: Acneiform, burning, delayed wound
healing, depigmentation, folliculitis, perioral
dermatitis, purpura, skin atrophy, steroid
rosacea, striae, telangiectasia.
Less Common: Allergic contact dermatitis.
Rare: Hyperesthesia, hypertrichosis, miliaria,
secondary infections, subcutaneous tissue
atrophy
Drug Interactions:
No generally recognized drug interactions
attributable to hydrocortisone that is used
topically (topical corticosteroids are less
likely to result in drug interactions than
those for systemic use).
Administration: Apply enough to cover the
affected area. Apply gently to the skin,
preferably after bathing.
Pregnancy Category: C
ANTISEPTICS AND DISINFECTANT
IODINE PRODUCTS
OTC POVIDINE-IODINE
Solution: 10% solution, 60 mL and 120 mL
bottle
10% ointment, 5 g and 15 g tube
10% paint, 10 mL bottle
7.5% surgical cleanser, 60 mL and
120 mL bottle
A brown-colored, antiseptic solution, which is
used for the disinfection of minor skin
infections.
Indications Skin disinfection; antiseptic;
treatment of common skin infections;
prevention of infection in minor burns,
lacerations, cuts, and abrasions; infection
control during insertion and care of urinary
catheters, circumcision, suture removal, and
dressing changes; degerming care of stasis
ulcers and umbilical area; treatment of
mouth sores (aphthous ulcers), herpes
simplex, herpes zoster (shingles), herpes
labialis (cold sores), grazes, abrasions, cuts,
and wounds, or any break in the skin which
requires protection from infection;
maximum degerming of skin as preoperative
preparation
Contraindications: Hypersensitivity to iodine;
postmenstrual age of 32 weeks; regular or
prolonged use in patients with thyroid
disorders, or those taking lithium; regular
use in neonates; in very low birth weight
infants (e.g., 1.5 kg); hyperthyroidism
Dose:
Prevention and treatment of infections, by
topical application, ADULT and CHILD, as
10% ointment, clean and dry affected area;
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DERMATOLOGICALS
apply liberally and cover with a dressing or
bandage; may be used as often as required;
use only as prescribed.
Mouth sores, herpes simplex, herpes zoster,
herpes labialis, grazes, abrasions, cuts, and
wounds, by topical application, ADULT and
CHILD, as 10% paint, apply undiluted to the
affected area and allow to dry; use twice
daily and cover with a dressing if desired.
Pre-operative and post-operative skin
disinfection, by topical application, ADULT
and CHILD, as 10% solution, apply an
appropriate volume of solution directly to the
skin area.
Antiseptic (minor wounds and burns), by
topical application, ADULT and CHILD, as
10% solution, apply an appropriate volume
of solution to the affected area, twice daily
(see Precautions below).
Degerming of skin on patients, by topical
application, ADULT, as 7.5% surgical
cleanser, apply necessary quantity on the
area to wash, thoroughly distribute while
rubbing for at least 5 minutes; rinse off with
a sterile gauze saturated with water.
Degerming of skin on health care personnel, by
topical application, ADULT, as 7.5% surgical
cleanser, apply necessary quantity on the
area to wash, thoroughly distribute while
rubbing for at least 5 minutes; clean under
fingernails using a brush if desired; rinse
under running water.
Precautions:
WARNING: Do NOT use 10% paint
preparation in children < 3 years old.
Broken skin; Renal impairment (avoid regular
application to inflamed or broken
mucosa); Pregnancy (second and third
trimesters: sufficient iodine may be
absorbed to affect the fetal thyroid).
Adverse Drug Reactions:
Rare: local irritation of the skin and mucous
membranes
Drug Interactions:
Page | 118
No information was found.
TEST INTERACTION. May interfere with thyroid
function tests due to systemic effects
Administration: For external use only. Apply
locally as needed.
Pregnancy Category: D
ATC Code: D08AG02
OTHER ANTISEPTICS AND
DISINFECTANTS
OTC ALCOHOL, ETHYL
Solution: 70% topical solution
A clear, aqueous solution of ethyl alcohol which
is used as a disinfectant and skin antiseptic.
Indications Disinfection of skin before
injection, venipuncture, or surgical
procedures
Contraindications: Management of broken
skin; patients who have suffered severe
burns when diathermy has been preceded
by application of alcoholic skin disinfectants
Dose:
Disinfection of skin, by topical application,
ADULT and CHILD, apply an appropriate
volume of solution directly to the skin area.
Precautions:
Avoid heat, sparks, and open flame and
temperatures above 30°C; Emission of
toxic fumes of carbon monoxide and
carbon dioxide, if exposed to fire.
Adverse Drug Reactions:
Skin dryness and irritation with frequent
application of the aqueous solution
DERMATOLOGICALS
Products with which hydrogen peroxide is
Drug Interactions: incompatible:
No information was found. Preparations containing Iodine,
Preparations containing Potassium
Administration: For external use only. Apply Permanganate
locally as needed.
Administration: For external use only. Apply
Pregnancy Category: No information was found locally as needed.

ATC Code: D08AX08 Pregnancy Category: No information found

ATC Code: D08AX01

OTC HYDROGEN PEROXIDE NOTE:

For information on antifungals, antilice and

antiscabies medicines, please refer to
Solution: 3%, 120 mL bottle Chapter 11: Antiparasitic Products,
Insecticides and Repellents.
A clear, colorless solution of hydrogen
peroxide, which is a powerful oxidizing
agent, and is used as a disinfectant.

Indications: Mild disinfectant for minor cuts,

skin ulcers, and wounds

Contraindications: Injection or instillation into

closed body cavities for which the released
oxygen has no free exit

Dose:
Disinfection, by topical application, ADULT and
CHILD, dress the wound with cotton wool
soaked in an appropriate volume of
hydrogen peroxide.

Precautions:
Use with caution in large or deep wounds;
Avoid contact with healthy skin, eyes, and
clothes.

Adverse Drug Reactions:

Rare: Hypersensitivity reactions, irritating
burns on the skin and mucous membranes
with a white eschar (strong solution)

Drug Interactions:
Avoid concomitant use with:

Page | 119
GENITO URINARY SYSTEM AND SEX HORMONES
seizure or delivery; treat recurrent seizure by
GENITO URINARY SYSTEM further IV bolus of 2 g or 4 g if bodyweight is
over 70 kg.
AND SEX HORMONES
Dose Adjustments:
Renal Impairment: Dose should not exceed 20
OTHER GYNECOLOGICALS g in 48 hours. Use with caution and
monitor for hypermagnesemia.

UTEROTONICS Precautions:
WARNING: Magnesium toxicity can cause
Prostaglandins loss of deep tendon reflexes, followed by
respiratory depression and ultimately
respiratory arrest. If deep tendon reflexes
MAGNESIUM SULFATE are absent, withhold further doses of
Rx (AS HEPTAHYDRATE)
magnesium sulfate until reflexes return. If
repeated seizures occur despite
magnesium, other pre-hospital options
Inj.: 250 mg/mL, 2 mL and 10 mL ampul (IM, include administering diazepam.
IV) Magnesium toxicity can be reversed with the
250 mg/mL, 20 mL vial (IV) administration of calcium gluconate,
administered as a 10–20 mL IV of 10%
500 mg/mL, 2 mL and 10 mL ampul (IM,
solution, as an antidote for problematic
IV)
signs associated with hypermagnesemia.
Magnesium is excreted by the kidney.
A sterile preparation that contains magnesium Monitor serum levels regularly in women
salt as heptahydrate. with oliguria (urine output).

Indications: Drug of choice for the prevention Myasthenia gravis; Hepatic impairment (avoid
of seizures in women with severe in hepatic coma if there is a risk of renal
preeclampsia; control of seizures or failure);
prevention of recurrence among eclamptic Renal impairment;
patients. Magnesium toxicity can lead to fatal
cardiovascular arrest and/or respiratory
Contraindications: Heart block; myocardial failure or paralysis;
infarction; hypermagnesemia; deranged Pregnancy.
renal function; myasthenia gravis
Adverse Drug Reactions:
Dose:
Common: Flushing, nausea, vomiting
Control of seizures and prevention of recurrent
Less Common: Dizziness, drowsiness,
seizures in eclamptic patients, by IV
headache, thirst
injection, ADULT, 4 g as loading dose over
Rare: Arrhythmias, cardiac arrest, coma,
5–15 minutes followed by IV infusion of
confusion, loss of tendon reflexes, muscle
maintenance dose of 1 g/hour for at least
weakness, respiratory depression
24 hours after the last seizure or delivery,
whichever occurs later.
NOTE: In this situation, magnesium toxicity can
By deep IM injection (used when IV lines are
present as follows: depressed deep tendon
not available), ADULT, 5 g into each buttock,
reflexes, cardiopulmonary arrest, and
then 5 g every 4 hours into alternate
respiratory depression.
buttocks for at least 24 hours after the last

Page | 120
GENITO URINARY SYSTEM AND SEX HORMONES
The toxicity arises from the blockage of IM Adult: Concentrations of 25%
calcium and potassium channels due to (250 mg/mL) or 50% (500
magnesium. mg/mL). Mix magnesium
Calcium gluconate treats hypermagnesemia sulfate, 50%, with 1 mL
by directly antagonizing magnesium at the lidocaine injection, 2%
neuromuscular junction. Child: Should not exceed 20%
(200 mg/mL)
For information on calcium gluconate, please
refer
to Chapter 1: Alimentary Tract and
Pregnancy Category: D
Metabolism and Chapter 2: Blood and Blood
Forming Organs ATC Code: Not available
Drug Interactions:
Monitor closely with:
Drugs that enhance the therapeutic effect of SEX HORMONES AND
Mg Sulfate: MODULATORS OF THE GENITAL
Aminoglycosides e.g., Streptomycin (additive
neuromuscular blocking effect), CNS
SYSTEM
Depressants, e.g., Barbiturates, Opiates,
General Anesthetics, Gabapentin (additive
central depressant effects), Neuromuscular
HORMONAL CONTRACEPTIVES FOR
Blockers e.g., Tubocurarine, SYSTEMIC USE
Succinylcholine, Vecuronium (potentiates
neuromuscular blockade), Nifedipine Progestins and estrogens, fixed
(Parenteral) combination
Drugs that increase the risk of adverse or toxic
effects of Magnesium Sulfate:
General Information
Nifedipine (hypotension)
Combination of hormonal contraceptives that
Administration:
For IV administration, do not exceed the rate of inhibit ovulation via a negative feedback
150 mg/minute. See manufacturer’s mechanism involving the hypothalamus.
directions for instructions on dilution and These modify the normal pattern of
administration. gonadotropin secretion of the follicle-
stimulating hormone (FSH) and luteinizing
NOTE: Should NOT be used via IV route for pre- hormone by the anterior pituitary. Thus,
eclampsia or eclampsia during 2 hours these inhibit the follicular phase FSH and
before delivery. the midcycle surge of gonadotropins. These
contraceptives also produce alterations in
Do NOT freeze since it may result in the genital tract, including changes in the
precipitation or crystallization. cervical mucus, making it unfavorable for
sperm penetration.
Route Preparation
Indication: Contraception
IV Concentration should NOT
exceed 20% (200 mg/mL).
Dilute 1part magnesium sulfate, Contraindications: Breast cancer (current or
50%, with at least 1.5 parts of recent); risk factors for venous
water for injection) thromboembolism and arterial disease;

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GENITO URINARY SYSTEM AND SEX HORMONES
heart disease associated with pulmonary
hypertension or risk of embolism; migraine; For Schedule 2:
history of subacute bacterial endocarditis; Sunday Begins dose on first
ischemic cerebrovascular disease; liver Starter Sunday after the onset of
disease, including disorders of hepatic menstruation. If the
secretion; porphyria; systemic lupus menstrual period starts on
erythematosus (SLE); history of hemolytic a Sunday, take the first
uremic syndrome; liver adenoma; tablet that very same day.
gallstones; estrogen-dependent neoplasm; With a Sunday start, an
neoplasm of the genital tract; undiagnosed additional method of
vaginal bleeding; history of pruritus during contraception should be
used until after the first 7
pregnancy, chorea, deteriorating
days of consecutive
otosclerosis, cholestatic jaundice, or
administration.
pemphigoid gestationis; after the
21- tablet Take 1 tablet daily for 21
evacuation of a hydatidiform mole; smokers package consecutive days, followed
>35 years by 7 days off the
medication. Start new
Dose: course on the 8th day after
ADMINISTRATION. Each tablet (“pill”) should the last tablet is taken.
be taken at approximately the same time 28- tablet Take 1 tablet daily without
each day. If one or more tablets are package interruption.
forgotten for more than 12 hours,
contraceptive protection will be reduced. NOTE: If all doses have not been taken on
schedule and one menstrual period is
For Schedule 1: missed, the possibility of pregnancy should
be considered. If 2 consecutive menstrual
Day 1 Take 1 tablet daily starting periods are missed, a pregnancy test is
Starter on the first day of the required before starting a new dosing cycle.
menstrual cycle.
21- tablet Take 1 tablet daily for 21
MISSED PILL. The critical time for loss of
package consecutive days, followed
contraception protection is when a pill is
by 7 days off the
medication (during which omitted either at the beginning or at the end
withdrawal bleeding of a cycle (as this lengthens the pill-free
occurs). Start new course interval). If a woman forgets to take a pill,
on the 8th day after the she should take it as soon as she
last tablet is taken. remembers, and take the next one at the
28- tablet Take 1 tablet daily without normal time.
package interruption (withdrawal If the delay with any pill is 24 hours or longer,
bleeding occurs when the pill may not work. Continue taking the pill
inactive tablets are being normally but be aware that contraception
taken). may not work for the next 7 days. If these 7
days run beyond the end of the packet, the
next packet should be started at once,
omitting the 7 inactive tablets or the pill-free
interval. Emergency contraception is
recommended if more than 2 combined oral
contraceptive tablets are missed from the
first 7 tablets in a packet.

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GENITO URINARY SYSTEM AND SEX HORMONES
DIARRHEA AND VOMITING. Vomiting within 2
hours of taking an oral contraceptive or very
severe diarrhea can interfere with the
absorption of the drug. Additional
precautions should be used during, and for
7 days after, recovery. If vomiting and
diarrhea occur during the last 7 pills, omit
inactive pills or the next pill-free period.
Dose Adjustment:
Renal Impairment
In mild-to-moderate impairment, use with
caution. In severe impairment, refer the
patient to a specialist.
Precautions:
WARNING: Increased risk of cardiovascular
side effects in women who smoke cigarettes
(especially heavy smokers with ≥15
cigarettes per day). Strongly advise women
who use combination hormonal
contraceptives to stop the use of oral
contraceptives or not to smoke.
Unexplained vaginal bleeding (investigate the
cause before starting contraceptive);
Risk factors for venous thromboembolism and
arterial disease;
Migraine without focal aura or controlled with
5HT1 agonist;
Hyperprolactinemia;
Gallbladder disease;
Some types of hyperlipidemia;
History of severe depression especially if
induced by hormonal contraception;
Long-term immobilization;
Sickle-cell disease;
Inflammatory bowel disease, including Crohn’s
disease;
Diabetes;
Smoking;
BMI >30;
Malabsorption syndromes;
Surgery;
Systemic Lupus Erythematosus (SLE);
Pregnancy (epidemiological evidence suggests
no harmful effects on fetus; use within 3
weeks of birth);
Breastfeeding (combined oral contraceptives
may inhibit lactation; use an alternative
method of contraception until weaning or for
6 months after birth).
MIGRAINE. Report any increase in headache
frequency or onset of focal symptoms.
Discontinue immediately and refer urgently
to a neurologist if focal neurological
symptoms not typical of aura persist for
more than 1 hour.
TRAVEL. Women may be at an increased risk of
deep-vein thrombosis during travel involving
long periods of immobility (over 5 hours).
The risk may be reduced by appropriate
exercise during the journey, and possibly by
wearing elastic hosiery.
Adverse Drug Reactions:
Common: Acne, breakthrough bleeding, breast
enlargement and tenderness, changes in
libido, chloasma, fluid retention, headache,
hypertension, mood changes (e.g.,
depression), nausea, thrush, vomiting
Less Common: Alopecia, amenorrhea, contact
lens intolerance, hirsutism,
hyperinsulinemia, insulin resistance, rash
Rare: Allergy, breast cancer, cervical cancer,
hypertension, jaundice, liver cancer,
pancreatitis, photosensitivity, stroke, VTE
Drug Interactions:
NOTE: Combined oral contraceptives are
metabolized by CYP3A4. Monitor closely
with:
Monitor closely with:
NSAIDs including COX-2 Inhibitors
(thrombogenic effect - Enhances therapeutic
effect of Fixed Combinations of Progestins
and Estrogens
Immune Globulin – With enhanced therapeutic
effect (thrombogenic effect)
Drugs that reduce contraceptive effect of Fixed
Combinations of Progestins and Estrogens:
Cephalosporins e.g. Ceftriaxone, Macrolide
Antibiotics e.g., Azithromycin, Erythromycin,
Metronidazole, Penicillin e.g.,
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GENITO URINARY SYSTEM AND SEX HORMONES
Benzylpenicillin, Amoxicillin,
Phenoxymethylpenicillin, Ampicillin,
Quinolones e.g., Ciprofloxacin, Levofloxacin,
Tetracyclines e.g. Doxycycline
Anti-diabetic Agents, Thyroid Products –
Therapeutic effects of these drugs are
reduced by these contraceptive pills
Avoid concomitant use with:
Drugs that decrease the serum concentration
of Fixed Combinations of Progestins and
Estrogens:
Bile Acid Sequestrants [administer oral
contraceptives at least 1-4 hours before or
4-6 hours after a Bile Acid Sequestrant],
Efavirenz, Lamotrigine, Topiramate
Tranexamic Acid - Enhances therapeutic effect
(thrombogenic effect)
Carbamazepine, CYP2C19 Inducers, CYP3A4
Inducers, Phenobarbital, Rifampicin -
Increases metabolism of Fixed
Combinations of Progestins and Estrogens
Drugs whose risk of adverse or toxic effects is
increased by these contraceptive pills:
Anti-hepaciviral Combination Products
(hepatotoxic effect), Vitamin K Antagonists,
e.g., Warfarin (thromboembolic disorders)
Drugs that reduce the therapeutic effect of
Fixed Combinations of Progestins and
Estrogens, leading to contraceptive failure:
Artemether, Barbiturates e.g. Phenobarbital,
Carbamazepine, CYP2C19 Inducers,
CYP3A4 Inducers, Fosphenytoin,
Mifepristone, Mycophenolate,
Phenobarbital, Phenytoin, Protease Inhibitor
[except Indinavir], Retinoic Acid Derivatives
[except Adapalene, Tretinoin (topical)],
Rifamycin Derivatives, Rifampicin
Drugs whose therapeutic effects are reduced:
Amlodipine, Enalapril, Isosorbide Dinitrate,
Methyldopa (antagonizes hypotensive
effect), Anastrozole, Anticoagulants e.g.
Warfarin, Heparin (counteracts
anticoagulant effects), Furosemide,
Hyaluronidase, Hydrochlorothiazide
(antagonizes diuretic effect), Metformin
(antagonizes hypoglycemic effect)
Page | 124
ETHINYLESTRADIOL
Rx + LEVONORGESTREL
Oral: 30 micrograms ethinylestradiol + 150
micrograms levonorgestrel per tablet
as 21 active tablets, or, 28- day tablet
with 21 active and 7 inactive pills
A combined, oral contraceptive, which contains
estrogen as ethinylestradiol and
progesterone as levonorgestrel. It inhibits
ovulation, reduces receptivity of the
endometrium for implantation, and thickens
cervical mucus that serves as a barrier to
sperm.
Indications: Contraception
Dose:
Contraception, by mouth, 1 tablet daily for 21
days starting on day 1 of the menstrual
cycle; repeat subsequent courses after a 7-
day tablet-free interval (during which
withdrawal bleeding occurs); or 28 tablets of
every day (ED) preparations, take 1 active
tablet daily starting on D1 of the cycle up to
D21; repeat subsequent courses without
interval (withdrawal bleeding occurs when
inactive tablets are being taken).
Administration: Take each pill at approximately
the same time each day. If delayed by longer
than 24 hours, contraceptive protection may
be lost.
See General Information on Progestins and
Estrogens, Fixed Combinations listed above
for further information.
Pregnancy Category: X
ATC Code: G03AA07
GENITO URINARY SYSTEM AND SEX HORMONES
Progestins
MEDROXYPROGESTERO
Rx
NE
Inj.: 50 mg/mL, 3 mL vial + syringe (IM) (as
acetate) (N.B. Use one (1) inch long needle)
A long-acting, progestin injectable
contraceptive indicated for the prevention of
pregnancy.
Indications: Parenteral progestin-only
contraception (short-term, long-term)
Contraindications: Pregnancy; undiagnosed
vaginal bleeding; history of pruritus during
pregnancy; active liver disease and history of
pruritus during pregnancy; severe arterial
disease; porphyria
Dose:
Contraception, by deep IM injection, ADULT
(female), short-term, 150 mg within the first
7 days of cycle or within the first 5 days after
parturition, delay until 6 weeks after
parturition if breastfeeding; long-term, by
deep IM injection, ADULT (female), as for
short-term, repeated every 3 months.
NOTE: If the interval between injections is >3
months and 14 days, exclude pregnancy
before administering the next injection and
advise the patient to use additional
contraceptive measures (e.g., a condom) for
7 days after the injection.
PATIENT ADVICE. Women should receive full
counseling on the likelihood of menstrual
irregularities and the potential for a delay in
return to full fertility with long-term use
before treatment
Dose Adjustments:
Hepatic Impairment: Use with caution. Avoid
use in active or severe liver disease
Precautions:
Unexplained vaginal bleeding (investigate the
cause before starting treatment);
History of endometriosis;
Uterine fibroids;
Migraine; Liver disease (avoid use in active
liver disease);
Thromboembolic or coronary vascular disease;
Diabetes Mellitus (monitor and adjust the dose
of antidiabetic drug if necessary);
Epilepsy;
Smoking;
Systemic Lupus Erythematosus (SLE);
Hypertension;
Renal disease;
Gall bladder disease;
Severe arterial disease (multiple risk factors
for venous thromboembolism and arterial
disease);
History of breast cancer (may be used after 5
years if no evidence of current disease);
Elderly; (increased risk of coronary heart
disease, stroke, VTE, and breast cancer);
Pregnancy (genital malformations and cardiac
defects have been reported in male and
female fetuses; inadvertent use of depot
contraceptive injection unlikely to harm
fetus; avoid use if there is a history of
pruritus during pregnancy);
Lactation (present in breastmilk; no adverse
effects reported; preferably start
injectable contraceptive 6 weeks after
birth or later)
Adverse Drug Reactions:
Common: Breast enlargement and tenderness,
change in libido, depression, endometrial
hyperplasia, headache, irregular or
breakthrough bleeding, leg cramps, spotting
Less Common: Acne, benign proliferative
breast disease, breast cancer, cardiovascular
events, dementia, edema, exacerbation or
recurrence of endometriosis, fluid retention,
gall stones, itch, migraine, nausea,
premenstrual-like syndrome
Rare: Chloasma, cholestatic jaundice,
endometrial cancer, enlargement of hepatic
hemangiomas, enlargement of uterine
Page | 125
GENITO URINARY SYSTEM AND SEX HORMONES
fibroids, galactorrhea, glucose intolerance,
hypersensitivity reactions, ovarian cancer,
pancreatitis, visual changes
Drug Interactions:
Avoid concomitant use with:
Metformin – Therapeutic effect of Metformin
is reduced (due to the antagonism of
hypoglycemic effect)
Administration:
If the interval between injections is >3 months
and 14 days, exclude pregnancy before
administering the next injection and advise
the patient to use additional contraceptive
measures (e.g. condom) for 7 days after the
injection.
Pregnancy Category: X
ATC Code: G03AC06
UROLOGICALS
DRUGS USED IN BENIGN PROSTATIC
HYPERTROPHY (BPH)
Alpha-adrenoceptor antagonists
General Information
Alpha–adrenoceptor blockers act
preferentially on the receptors in the lower
urinary tract resulting to relaxation in the
muscles of bladder and prostate.
Indications: Treatment of signs and symptoms
of benign prostatic hypertrophy and relief of
symptoms of urinary obstruction
Precautions:
Hypotension;
Volume depletion;
Renal impairment;
Hepatic impairment;
Page | 126
Patients who are receiving an antihypertensive
treatment may require dose reduction and
supervision;
Monitor for an improved urine flow and for
“first dose” orthostatic hypotension,
headache, or GI disturbances, e.g., nausea,
vomiting, at the beginning of therapy and on a
regular basis;
Elderly and patients undergoing cataract
surgery (risk of intraoperative floppy iris
syndrome)
Drug Interactions:
Monitor closely with:
Drugs that enhance therapeutic effect of
Alpha-adrenoceptor Antagonists:
Anti-hypertensives, Calcium Channel
Blockers (hypotensive effect), Cimetidine
Drugs that enhance therapeutic effect of
Alpha-adrenoceptor Antagonists:
Nitroglycerin (hypotensive effect),
Phosphodiesterase Inhibitors (hypotensive
effect)
Drugs that increase risk of adverse or toxic
effects of Alpha-adrenoceptor Antagonists:
Beta Blockers (orthostatic hypotension),
CYP3A4 Inhibitors, e.g., Ketoconazole,
Itraconazole, Ritonavir, Dapoxetine
(orthostatic hypotension), MAO Inhibitors
[except Linezolid] (orthostatic hypotension)
Drugs that reduce therapeutic effect of Alpha-
adrenoceptor Antagonists:
Alpha / Beta Agonists (vasoconstricting
effect), Bosentan, CYP3A4 Inducers,
Deferasirox, Tocilizumab
Avoid concomitant use with:
Drugs that decrease serum concentration of
Alpha-adrenoceptor Antagonists:
CYP3A4 Inducers, Dabrafenib
Drugs that enhance therapeutic effect of
Alpha-adrenoceptor Antagonists:
Alpha1 Blockers (antihypertensive effect),
Phosphodiesterase-5 Inhibitors e.g.
Sildenafil (antihypertensive effect), Protease
Inhibitors e.g., Indinavir
QTc-prolonging Agents – Alpha-adrenoceptor
blockers enhance its therapeutic effect
(highest risk)
GENITO URINARY SYSTEM AND SEX HORMONES
Drugs that increase risk of adverse or toxic
effects of Alpha-adrenoceptor Antagonists:
Beta-Blockers [CYP3A4 Inhibitors, Fusidic
Acid, Mifepristone (orthostatic hypotension),
Drugs that increase the serum concentration
of Alpha-adrenoceptor Antagonists:
CYP3A4 Inhibitors, Fusidic Acid
TAMSULOSIN
Rx
Oral: 200 micrograms capsule (as
hydrochloride)
An alpha1-selective adrenoceptor antagonist
used in BPH to relieve symptoms of urinary
obstruction, including acute urinary
retention.
Indications: For lower urinary tract symptoms
(LUTS) associated with BPH; treatment of
signs and symptoms of BPH and relief of
symptoms of urinary obstruction
Dose:
Benign prostatic hypertrophy, by mouth,
ADULT, 1 mg every bedtime; may gradually
increase at 7-day intervals according to
response; (maintenance dose, 5–10 mg
once every bedtime).
Adverse Drug Reactions:
Common: Dizziness, asthenia
Less Common: Hypotension, rhinitis, light-
headedness, somnolence, palpitation,
nausea, edema, sinusitis, dyspnea, fatigue,
headache, back pain, flu-like syndrome,
tachycardia, amblyopia, blurred vision,
impotence, syncope
Administration: Administer with or without food
once daily at bedtime. Give first dose and
subsequent increase at bedtime to prevent
syncope.
See General Information on Alpha-
Adrenoceptor Antagonists under Drugs used
in Benign Prostatic Hypertrophy listed above
for further information.
Pregnancy Category: B
ATC Code: G04CA02
TESTOSTERONE-5-ALPHA
REDUCTASE INHIBITORS
FINASTERIDE
Rx
Oral: 5 mg tablet
A type II 5-alpha reductase inhibitor with anti-
androgenic properties due to the conversion
of testosterone to dihydrotestosterone.
Indications: Management of BPH; reduction of
incidence of acute urinary retention and
need for surgery
NOTE: Although effective in partially relieving
lower urinary tract symptoms, therapy with
an alpha1-adrenergic blocker appears to
result in greater improvement in symptoms.
Contraindications: Pregnant or women of
childbearing age
Dose:
Benign prostatic hypertrophy, by mouth,
ADULT, initially 1 mg at bedtime, subsequently
increase stepwise to 2, 5, or 10 mg once
daily, as single drug or in combination, at 7-
day intervals.
NOTE: A minimum of 6 months of treatment
may be necessary to determine if an
individual will respond to finasteride.
Page | 127
GENITO URINARY SYSTEM AND SEX HORMONES
Administration: May be administered with or
without meals.
Dose Adjustment:
Hepatic Impairment: Pregnancy Category: X
Use with caution. Finasteride is metabolized
extensively in the liver. ATC Code: G04CB01

Precautions:
WARNING: Decreases concentration of
serum markers of prostate cancer such
as the Prostate Specific Antigen (PSA) by
up to 50% even if cancer is present.
Adjust reference values accordingly.

Carefully monitor patients with severely

diminished urinary flow;
Hepatic impairment (metabolized extensively
in the liver);
Men at risk of obstructive uropathy;
Rule out prostate cancer before initiating
treatment;
Pregnancy (women of childbearing age should
not touch or handle crushed or broken
tablets; active ingredients of crushed or
broken tablets can be absorbed through the
skin and may negatively impact fetal
development).

Adverse Drug Reactions:

Common: Orthostatic hypotension, dizziness,
decreased libido, impotence,
neuromuscular and skeletal weakness
Less Common: Edema, drowsiness, skin rash,
gynecomastia, decreased ejaculate
volume, breast tenderness, dyspnea,
rhinitis
Rare: Altered mental status; change in libido,
decreased testicular size, depression,
disturbed sleep, hypersensitivity
(angioedema, facial swelling, pharyngeal
edema, pruritus, skin rash, swelling of the
lips, swollen tongue, urticaria), male
infertility (temporary), malignant neoplasm
of the male breast, prostate cancer high
grade, prostatitis, reduction in penile
curvature, reduction in penile size, sexual
disorder (may not be reversible with
discontinuation), testicular pain

Drug Interactions: No known significant

interactions

Page | 128
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Stress (may require higher doses when
SYSTEMIC HORMONAL subject to stress, i.e., trauma, surgery,
severe infection); Elderly; Children;
PREPARATIONS, Pregnancy (use in early pregnancy may
EXCLUDING SEX slightly increase the risk of orofacial clefts);
Lactation (allow a 4-hour interval between
HORMONES AND INSULIN administration and breastfeeding)
.
Adverse Drug Reactions: Arrhythmia,
GLUCOCORTICOIDS bradycardia, cardiac arrest,
cardiomyopathy, CHF, circulatory
collapse, edema, hypertension,
CORTICOSTEROIDS FOR myocardial rupture (post-MI), syncope,
SYSTEMIC USE thromboembolism, vasculitis,
depression, euphoria, emotional
instability, headache, increased
intracranial pressure, insomnia,
GENERAL INFORMATION malaise, neuritis, mood swings,
personality changes, pseudotumor
Glucocorticoids act as an anti-inflammatory cerebri (following discontinuation),
agent by suppressing the release of seizure, psychic disorders, vertigo,
inflammatory proteins. It also aids in the allergic dermatitis, acne, alopecia,
biological response to stress, which angioedema, bruising, dry skin,
includes the mobilization of fat and sugar erythema, fragile skin, hypertrichosis,
stores in the body. hirsutism, hyperpigmentation or
hypopigmentation, rash, perianal
Mode of Action: Glucocorticoids mimic the pruritus (following IV injection),
actions of corticosteroids produced in the petechiae, skin atrophy, impaired skin
adrenal cortex and naturally found in the test reaction, striae, urticaria, impaired
body. wound healing, adrenal suppression,
decreased carbohydrate tolerance and
glucose intolerance, Cushing's
Dose Adjustment:
syndrome, diabetes mellitus, growth
Geriatric: suppression (children), hypokalemic
alkalosis, hyperglycemia, menstrual
Use the smallest effective dose for the shortest irregularities, negative nitrogen balance,
duration possible. protein catabolism, pituitary-adrenal axis
suppression, sodium retention,
Precautions: abdominal distention, increased
Adrenal suppression; Anaphylactoid reactions; appetite, GI hemorrhage, GI perforation,
Diabetes; Immunosuppression; Latent TB; pancreatitis, peptic ulcer, ulcerative
Kaposi sarcoma; Myopathy; Myasthenia esophagitis, weight gain; altered
gravis; Psychiatric disturbances; Seizure spermatogenesis, hepatomegaly,
disorders; Cardiovascular disease; increased transaminases, nausea,
Myocardial infarction; GI disease (avoid arthropathy, aseptic necrosis (femoral
ethanol since this may enhance gastric and humoral heads), fractures, muscle
mass loss, myopathy (in conjunction with
mucosal irritation); Head injury (high doses
neuromuscular disease or
should not be used for management of neuromuscular-blocking agents),
head injury); Ocular disease; Hepatic thrombophlebitis, neuropathy,
impairment i.e., cirrhosis and renal osteoporosis, paresthesia, tendon
impairment; Osteoporosis; Thyroid disease; rupture, weakness, vertebral

Page | 129
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
compression fractures, cataracts,
exophthalmos, glaucoma, increased
intraocular pressure, glucosuria,
pulmonary edema, abnormal fat Drug Interactions:
deposition, anaphylactoid reaction, Monitor closely with:
anaphylaxis, avascular necrosis, Warfarin – Dexamethasone enhances the
diaphoresis, hiccups, hypersensitivity, therapeutic effect (anticoagulant effect)
impaired wound healing, infections, of Warfarin
Kaposi's sarcoma, moon face, Drugs that increase the risk of adverse or toxic
secondary malignancy effects of Dexamethasone:
Salicylates (GI ulceration and bleeding)
Drugs whose risk of adverse or toxic effects
may be increased:
DEXAMETHASONE
Rx Acetylcholinesterase Inhibitors e.g.
pyridostigmine edrophonium (increased
muscular weakness), Amphotericin B,
Thiazide Diuretics, Loop Diuretics
Oral: 500 micrograms and 4 mg tablet (hypokalemic effect), Androgens (fluid-
Inj.: 5 mg/mL (as sodium phosphate), 1 mL retaining effect), COX-2 Inhibitors e.g.
ampule (IM, IV) Celecoxib, NSAID (Non-selective),
A corticosteroid with mainly glucocorticoid Quinolone Antibiotics e.g. Levofloxacin
activity, but lacks mineralocorticoid (tendonitis; tendon rupture),
properties Bile Acid Sequestrants - Reduce absorption of
Dexamethasone
Reduces the diagnostic effect of the following
Indications: Fetal lung maturation for women agents:
at risk for pre-term birth; management of Coccidioides immitis Skin Test
a wide variety of inflammation and Drugs whose therapeutic effect may be
allergic disorders responsive to reduced by dexamethasone:
corticosteroid therapy; second-line Antidiabetic Agents, Calcitriol,
management of asthma and related Corticorelin (blunts plasma ACTH
bronchospastic disorders. response to corticorelin), Urea Cycle
Disorder Agents (increases protein
Contraindications: Systemic fungal infections; catabolism and plasma ammonia
cerebral malaria. concentrations, increasing doses of
Urea Cycle Disorder Agents needed to
Dose: maintain concentrations in the target
Fetal lung maturation for women at risk for pre- range)
term labor;
Anti-inflammatory, by mouth or by IM or IV Avoid concomitant use with:
injection, ADULT, 0.75–9 mg daily in Antacids – decreases the bioavailability of
divided doses every 6–12 hours. dexamethasone [separate doses by at
Anti-inflammatory or immunosuppressant, by least 2 hours]
mouth or by IM or IV injection, CHILD, Phenytoin – decreases serum concentration
0.08–0.3 mg/kg daily or 2.5–10 mg/m2 Drugs whose serum concentration can be
daily in divided doses every 6–12 hours. decreased by dexamethasone:
Imatinib [increase Imatinib dose by at
Adverse Drug Reactions: (See General least 50%], Phenytoin, Ticagrelor
Information for more information on the [including its active metabolites],
adverse drug reactions of Vincristine
Glucocorticoids) Non-depolarizing Neuromuscular-Blocking
Agents e.g., Pancuronium, Atracurium
Page | 130
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
(neuromuscular effect) – Enhance the
therapeutic effect of dexamethasone
Thalidomide – Therapeutic effect may be
enhanced by dexamethasone
(thrombogenic effect)
Drugs increasing risk of adverse or toxic effects
of Dexamethasone:
Nondepolarizing Neuromuscular-
Blocking Agents, (increased muscle
weakness, possibly progressing to
polyneuropathies and myopathies)],
Tacrolimus, Topical
Drugs whose risk of adverse or toxic effects
may increase:
Thalidomide (dermatologic adverse
effect), Vaccines (Live)
Drugs whose therapeutic effect may be
reduced:
BCG, Hyaluronidase, Vaccines
(Inactivated [complete all
appropriate vaccinations at least 2
weeks before starting Dexamethasone;
if vaccinated during Dexamethasone
therapy, revaccinate at least 3 months
after discontinuation]),
Unknown impact on the therapeutic effect of
the following drugs:
Budesonide EC Tablets (could dissolve
prematurely if given with drugs that
lower gastric acid)
Administration:
See General Information on Corticosteroids for
Systemic Use – Glucocorticoids listed
under Systemic Hormonal Preparations
for further information.
Pregnancy Category: C
ATC Code: H02AB02
HYDROCORTISONE
Rx
Inj.: 50 mg/mL, 2 mL vial (IM, IV)
(as sodium succinate)
125 mg/mL, 2 mL and 4 mL vial (IV)
(as sodium succinate)
Powder, 100 mg, 250 mg (IV)
(as sodium succinate)
A glucocorticoid used for replacement therapy
in adrenal insufficiency, management of
autoimmune and inflammatory
conditions, and emergency
management of anaphylaxis and severe
systemic allergies.
Indications: Management of autoimmune or
inflammatory conditions;
hypersensitivity reactions such as
anaphylactic shock and angioedema;
treatment of acute and severe asthma.
NOTE: This is also used for acute adrenal insufficiency
for which referral to a specialist is warranted.
Contraindications: Systemic fungal infections;
serious infections, except septic shock
age- or tuberculous meningitis; viral, fungal,
or tubercular skin lesions; infective
arthritis, skin or soft tissue infections
near joints or a prosthetic joint;
concurrent administration of live virus
vaccines and immunosuppressive doses
of corticosteroids; IM administration in
idiopathic thrombocytopenia purpura;
intrathecal administration.
NOTE: Corticosteroids given IM are contraindicated for
idiopathic thrombocytopenic purpura; they are
also contraindicated for intrathecal
administration.
Dose:
Acute severe asthma, by IV injection, ADULT,
100 mg every 6 hours; CHILD, 4 mg/kg
every 4 to 6 hours. (See under
Respiratory System for more information
for dosing information)
Anti-inflammatory, by IV or IM injection, ADULT,
100-500 mg 3 or 4 times daily; CHILD, 2-
4 mg/kg every 6 hours for 24 hours, then
reduce over subsequent 24 hours, or
change to oral prednisone.
Dose Adjustments:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist; use with caution.
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SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Precautions:
Injection into the deltoid muscle (avoid due to
high incidence of subcutaneous
atrophy); the lowest possible dose of
corticosteroid should be used to control
the condition under treatment
(whenever reduction is possible, it
should be gradual);
Peptic ulcer disease (increase the risk of
perforation); myasthenia gravis
(increased muscle weakness); large
doses of corticosteroids can cause
elevation of BP, salt and water retention,
and increased potassium and calcium
excretion; osteoporosis (increased risk
of fractures and accelerates bone loss);
heart failure, hypertension (may be
worsened);
Chronic use may result in hypothalamic-
pituitary adrenal axis suppression,
Cushing’s syndrome, and hyperglycemia;
diabetes (avoid extensive use as
systemic absorption can increase blood
glucose concentration); psychiatric
disorders (may be exacerbated);
children (possible growth retardation);
immunocompromised patients
(increased risk and severity of infection);
latent TB (may be reactivated).
Pregnancy (corticosteroid use in early
pregnancy may slightly increase the risk
of orofacial clefts).
Adverse Drug Reactions:
Common: Acne, adrenal suppression,
amenorrhea, bruising, delayed wound
healing, dyslipidemia, dyspepsia,
edema, fat redistribution, fractures,
growth retardation, hirsutism,
hyperglycemia, hypertension,
hypokalemia, increased appetite,
increased susceptibility to infection,
masking of signs of infection, muscle
weakness and wasting, myopathy,
osteoporosis, psychiatric effects, skin
atrophy, sodium and water retention,
weight gain.
Less Common: Glaucoma, ocular
hypertension, osteonecrosis, particularly
of the femoral and humeral heads.
Rare: Anaphylactoid reaction,
chorioretinopathy (central), euphoria,
Page | 132
hypersensitivity reactions, hypomania,
peptic ulceration, tendon rupture.
Drug Interactions:
NOTE: Hydrocortisone is a substrate for CYP3A-based
interactions; its concentration may be affected
by the presence of enzyme inducers and
inhibitors (see Appendix).
Monitor closely with:
Acetylsalicylic acid and other salicylates –
increased risk of GI bleeding and
ulceration; corticosteroids may also
decrease plasma salicylate
concentration.
Antifungal Agents (e.g., azole derivatives) –
these may reduce the metabolism of
corticosteroids.
Contraceptives, Oral – contraceptives which
contain estrogens increase the plasma
concentration of hydrocortisone.
Digoxin – increased risk of hypokalemia, which
may lead to arrhythmias.
Drugs reducing potassium concentration (e.g.,
amphotericin B and diuretics) – systemic
corticosteroids reduce potassium
concentration, increasing the risk of
hypokalemia; also, if corticosteroids are
given with these drugs, there is an
enhanced risk of adverse effects.
Drugs increasing blood glucose concentration
(e.g., antipsychotics, calcineurin
inhibitors, and high-dose thiazide
diuretics) – glucocorticoids can increase
blood glucose concentration and may
increase the risk of hyperglycemia if
given with these drugs.
Ibuprofen – increased risk of GI bleeding and
ulceration.
Macrolide antibiotics (e.g., erythromycin) –may
cause a significant decrease in
clearance of corticosteroids.
Phenytoin – this increases the metabolism of
corticosteroids, possibly reducing their
activity.
Rifampicin – this increases the metabolism of
corticosteroids, possibly reducing their
activity.
Salbutamol – increased risk of hypokalemia.
Avoid concomitant use with:
Amlodipine – antagonism of hypotensive
effect.
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Antihypertensives (e.g., enalapril, isosorbide
dinitrate, and methyldopa) – antagonism
of hypotensive effect.
Calcium salts – there is reduced absorption of
calcium salts.
Diuretics (e.g., furosemide,
hydrochlorothiazide) – hydrocortisone
antagonizes the diuretic effect of these
drugs; possibly increased the risk of
hypokalemia.
Drugs controlling blood glucose concentration
– hydrocortisone may increase blood
glucose concentration and may alter the
control of diabetes.
Vaccine, Influenza – corticosteroids impair
immune response, and may reduce the
therapeutic effect of the vaccine.
Vaccine, Live – corticosteroids impair immune
response, and may enhance the adverse
effect of the vaccines (live).
Administration: Give directly, or dilute in
normal saline or D5W; administer within
24 hours after diluting.
Pregnancy Category: C; D in the 1st trimester.
ATC Code: H02AB09
METHYLPREDNISOLONE
Rx
Oral: 4 mg and 16 mg tablet
A synthetic glucocorticoid used principally as
an anti-inflammatory or immuno-
suppressant agent.
Indications: For the suppression of
inflammatory and allergic disorders,
rheumatic diseases, and various skin
disorders.
Contraindications: Systemic fungal infection;
formulations containing benzyl alcohol
preservative are contraindicated in
premature infants; IM administration in
idiopathic thrombocytopenic purpura;
intrathecal administration
Dose:
Anti-inflammatory or immunosuppressive,
by mouth, ADULT, initially mg daily in 1–4
divided doses, followed by a gradual
reduction in dose to the lowest effective
dose;
by mouth or by IM or IV injection, CHILD, as
sodium succinate, 0.5–1.7 mg/kg daily or
5–25 mg/m2 daily in divided doses every
6–12 hours (“pulse” therapy may also be
given at 15–30 mg/kg per dose for at least
30 minutes given once daily for 3 days).
Allergic condition, by mouth, ADULT, dosing is
individualized based on the disease severity
and the patient response. The usual oral
initial dose ranges from 4 mg to 48 mg once
a day (for lower doses), or in divided doses
(for higher doses). The dose is adjusted or
maintained until a satisfactory response is
maintained. Then, gradually in small
decrements at appropriate intervals,
decrease to the lowest dose that maintains
an adequate clinical response. Tapering
may be done over a few to 12 days.
Asthma exacerbations, including status
asthmaticus, emergency medical care or
hospital doses, by mouth or IV injection,
ADULT, 32–64 mg daily in 1–2 divided
doses until peak expiratory flow is 70% of
predicted or personal best; CHILD ≥12
years, 32–48 mg/kg daily in 2 divided doses
until symptoms resolve and peak expiratory
flow is 80% of predicted or personal best;
CHILD <12 years, 0.8–1.6 mg/kg daily in 2
divided doses (maximum, 60 mg daily), until
peak expiratory flow is 80% of predicted or
personal best.
Severe persistent asthma or long-term control,
by mouth, ADULT and CHILD ≥12 years, 6–
48 mg once daily or every other day as
needed for asthma control; CHILD <12
years, 0.2–1.6 mg/kg once daily or every
other day as needed for asthma control
(maximum dose, 48 mg).
Adverse Drug Reactions:
Common: Arrhythmias, bradycardia, cardiac
arrest, cardiomegaly, congestive heart
failure, edema, hypertension, hypertrophic
Page | 133
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
cardiomyopathy (premature infants),
myocardial rupture (post-MI), fat embolism, Drug Interactions:
syncope, tachycardia, thromboembolism, Monitor closely with:
vasculitis, delirium, depression, emotional Warfarin – Therapeutic effect may be
instability, euphoria, hallucinations, enhanced (anticoagulant effect)
headache, increased intracranial pressure, Salicylates - increases the risk of adverse or
insomnia, malaise, mood swings, toxic effects of Methylprednisolone (GI
nervousness, neuritis, personality changes, ulceration or bleeding)
psychic disorders, pseudotumor cerebri Drugs whose risk of adverse or toxic effects
(following discontinuation), seizure, vertigo, increase:
acne, allergic dermatitis, alopecia, dry scaly Acetylcholinesterase Inhibitors (increased
skin, ecchymoses, edema, erythema, muscular weakness), Amphotericin B
hyperpigmentation or hypopigmentation, (hypokalemic effect), Androgens (fluid-
rash, hirsutism, hypertrichosis, impaired retaining effect), COX-2 Inhibitor,
wound healing, petechiae, skin atrophy, Deferasirox (GI ulceration or irritation; GI
sterile abscess, impaired skin test reaction, bleeding), Loop Diuretics (hypokalemic
effect), NSAIDs (Non-selective), Quinolone
striae, urticaria, adrenal suppression,
Antibiotics (tendonitis; tendon rupture),
amenorrhea, increased carbohydrate
Thiazide Diuretics (hypokalemic effect)
intolerance, Cushing's syndrome, diabetes Bile Acid Sequestrants - Reduces absorption of
mellitus, fluid retention, glucose Methylprednisolone
intolerance, growth suppression (children), Reduces the diagnostic effect of Coccidioides
hyperglycemia, hyperlipidemia, immitis Skin Test
hypokalemia, menstrual irregularities, Drugs whose therapeutic effects are reduced:
negative nitrogen balance, pituitary-adrenal Antidiabetic Agents, Calcitriol (Systemic),
axis suppression, protein catabolism, Corticorelin (blunts plasma ACTH response
sodium and water retention, abdominal to Corticorelin), Urea Cycle Disorder Agents
distention, increased appetite, GI (increases protein catabolism and plasma
hemorrhage, GI perforation, nausea, ammonia concentrations, increasing doses
pancreatitis, peptic ulcer, perforation of the of Urea Cycle Disorder Agents needed to
small and large intestine, ulcerative maintain concentrations in target range)
esophagitis, vomiting, weight gain,
leukocytosis (transient); hepatomegaly, Avoid concomitant use with:
thrombophlebitis, arthralgia, arthropathy, Antacids - decrease the bioavailability of
aseptic necrosis (femoral and humoral Methylprednisolone [separate doses by at
heads), fractures, muscle mass loss, least 2 hours]
muscle weakness, myopathy (in Neuromuscular-blocking agents [Non-
depolarizing (increased muscle weakness,
conjunction with neuromuscular disease or
possibly progressing to polyneuropathies
neuromuscular-blocking agents), and myopathies)], Tacrolimus - Increases
neuropathy, osteoporosis, paresthesia, risk of adverse or toxic effects of
tendon rupture, vertebral compression Methylprednisolone
fractures, weakness, cataracts, glaucoma, Vaccines (Live) - the risk of adverse or toxic
glycosuria, pulmonary edema, abnormal fat effects are increased
disposition, anaphylactoid reaction, Drugs whose therapeutic effects are reduced:
angioedema, avascular necrosis, BCG (Intravesical), Hyaluronidase, Vaccines
anaphylaxis, increased intraocular (Inactivated [complete all age-appropriate
pressure, diaphoresis, hiccups, vaccinations at least 2 weeks before
hypersensitivity reactions, infections, starting Dexamethasone; if vaccinated
exophthalmoses, secondary malignancy during Dexamethasone therapy,
Rare: Venous thrombosis

Page | 134
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
revaccinate at least 3 months after
discontinuation]), Vaccines (Live)
Unknown impact on the therapeutic effect of
Budesonide EC Tablets (could dissolve
prematurely if given with drugs that lower
gastric acid)
See General Information on Corticosteroids for
Systemic Use – Glucocorticoids listed under
Chapter 6: Systemic Hormonal
Preparations for further information.
Pregnancy Category: C
ATC Code: H02AB04
PREDNISONE
Rx
Oral: 5 mg, 10 mg and 20 mg tablet
10 mg/5 mL suspension, 60 mL
A corticosteroid with glucocorticoid and anti-
inflammatory effects that can suppress
adrenal function at high doses. It is
rapidly converted to prednisolone in the
body. Its antitumor effects may be
related to the inhibition of glucose
transport, phosphorylation, or induction
of cell death in immature lymphocytes.
Its antiemetic effects are thought to
occur due to the blockade of cerebral
innervations of the emetic center by
inhibiting prostaglandin synthesis.
Indications: Management of autoimmune
disease; short-term suppression of
inflammation in allergic disorders; atopic
dermatitis; acute severe asthma
(reliever); severe persistent asthma not
responding to high-dose inhaled
steroids, long-acting agonists, and
methylxanthines (controller);
Contraindications: Known hypersensitivity to
any component of the formulation;
untreated systemic fungal infections;
administration of live or live, attenuated
virus vaccines with immunosuppressive
doses of prednisone.
Dose:
NOTE: No definitive treatment guidelines exist.
Dosing is dependent on institution
protocols and individual responses.
General dosing range, by mouth, Initial: 5-60
mg daily.
RECOMMENDATIONS ON APPROPRIATE USE:
• Before use, the dose and duration of treatment
should be based on the risk versus benefit for
each patient. Generally, use the smallest
effective dose for the shortest duration of time
to minimize the adverse events. A gradual
tapering of dose may be required before
discontinuing therapy.
• Dosage for infants and children should be
based on the severity of the disease and
response of the patient rather than on strict
adherence to dosage indicated by age, weight,
or body surface area.
• A gradual tapering of dose may be required
before discontinuing therapy.
• Discontinuing especially of long-term therapy
requires gradual withdrawal. Abrupt withdrawal
may precipitate acute adrenal insufficiency.
• Tapering of the steroid dose should be
individualized depending on the disease and
severity of the condition. For example, the dose
may be tapered off by 10-20% every 3 to 5 days
and once a dose of 10 mg per day is reached,
a slower weekly tapering is recommended.
• Consider alternate day therapy for long-term
therapy (to reduce adverse effects).
Autoimmune or inflammatory disease, by
mouth, ADULT, initially 5-60 mg once
daily depending on the disease and its
severity. Adjust dose according to
response and to recommended
guidelines; CHILD, initially 1-2 mg/kg
once daily (usual maximum dose, 60 mg)
with dose adjustments based on
guidelines.
Acute asthma, by mouth, ADULT, 40–60 mg
daily for 3–10 days as a single dose or in
2 divided doses; CHILD <12 years, 1–2
mg/kg daily for 3–10 days, with a
maximum of 60 mg daily.
Rheumatoid arthritis, by mouth, ADULT, ≤10
mg daily. NOTE: Once the condition has
stabilized, reduce to the minimum required to
maintain control of the disorder.
Dose Adjustment:
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SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
GI disease, e.g., diverticulitis, peptic ulcer, and
ulcerative colitis (increased risk of
perforation); myasthenia gravis
(increased muscle weakness); large
doses can cause elevation of BP, salt
and water retention and increased
potassium and calcium excretion;
osteoporosis; heart failure, hypertension
myocardial infarction; chronic use may
result in hypothalamic-pituitary adrenal
axis suppression, Cushing’s syndrome,
and hyperglycemia; diabetes; posterior
subcapsular cataracts, glaucoma ocular
infections; psychiatric disturbances,
such as depression, euphoria, insomnia,
mood swing, and personality changes;
possibly cause Kaposi’s sarcoma; acute
myopathy; seizure disorders; thyroid
disease; hepatic impairment.
Immunocompromised patients (increase the
risk and severity of infection); may
increase secondary infection, mask
acute infection (including fungal
infections), prolong or exacerbate viral
infections, or limit response to vaccines;
should not be used to treat ocular
herpes simplex or cerebral malaria;
exposure to chickenpox should be
avoided; close observation is required in
patients with latent TB and/or TB
reactivity; restrict use in active TB (only
in conjunction with antituberculosis
treatment).
Pediatrics (may affect growth velocity; growth
should be routinely monitored); and
breastfeeding (take the dose
immediately after a feed and wait 4
hours before the next feed).
Adverse Drug Reactions:
Common: Acne, adrenal suppression,
amenorrhea, bruising, delayed wound
healing, dyslipidemia, dyspepsia,
edema, fat redistribution, fractures,
growth retardation, hiccups, hirsutism,
hyperglycemia, hypertension,
Page | 136
hypokalemia, increased appetite,
increased susceptibility to infections,
malaise, masking of signs of infection,
muscle weakness and wasting,
myopathy, nausea, osteoporosis,
psychiatric effects, skin atrophy, sodium
and water retention, weight gain.
Less Common: Glaucoma, ocular
hypertension, osteonecrosis or aseptic
necrosis (particularly of the femoral and
humeral heads).
Rare: Anaphylactoid reaction,
chorioretinopathy (central), euphoria,
hypersensitivity reactions, hypomania,
peptic ulceration, tendon rupture.
Drug Interactions:
NOTE: Prednisone is a substrate for CYP3A-based
interactions; its concentration may be affected
by the presence of enzyme inducers and
inhibitors (see Appendix).
Monitor closely with:
Acetylsalicylic acid and other salicylates –
increased risk of GI bleeding and
ulceration; corticosteroids may also
decrease plasma salicylate
concentration
Drugs increasing blood glucose concentration
(e.g., antipsychotics, calcineurin
inhibitors, high-dose thiazide diuretics,
somatropin) – glucocorticoids can
increase blood glucose concentration
and may increase the risk of
hyperglycemia if given with these drugs.
NSAIDs – oral corticosteroids increase the risk
of gastric ulceration.
Phenytoin – this increases the metabolism of
corticosteroids, possibly reducing their
activity.
Rifampicin – this increases the metabolism of
corticosteroids, possibly reducing their
activity.
Avoid concomitant use with:
Antacids (e.g., aluminum or magnesium
hydroxide) – may decrease the
bioavailability of oral corticosteroids.
BCG vaccine – immunosuppressants may
reduce the therapeutic effect of BCG.
Drugs controlling blood glucose concentration
– prednisone may increase blood
glucose concentration and may alter the
control of diabetes (diminish the
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
hypoglycemic effect of antidiabetic Prevention of postpartum hemorrhage, by slow
agents). IM injection, ADULT and ADOLESCENT, 5
IU when the anterior shoulder is
Administration: Taking it early in the morning delivered or immediately after birth.
reduces possible side effects. Treatment of postpartum hemorrhage, by slow
IV injection, ADULT and ADOLESCENT, 5-
For oral administration, take after meals 10 IU or by IM injection, ADULT and
or with food or milk to decrease GI ADOLESCENT, 10 IU, followed in severe
effects. Increased dietary intake of cases by a total of 40 IU, by intravenous
pyridoxine, vitamins A, B6, C, D, folate, infusion, at a rate of 0.02-0.04
calcium, zinc, and phosphorus is also IU/minute; this should be started after
recommended. the placenta is delivered.
DILUTION AND ADMINISTRATION. According to
Pregnancy Category: C; D in the 1st trimester. the manufacturer’s directions.
Prolonged IV administration at high
ATC Code: H02AB07 doses with a large volume of fluid (e.g.,
in inevitable or missed abortion, or in
postpartum hemorrhage) may cause
water intoxication with hyponatremia. To
OXYTOXIC avoid this, use electrolyte-containing
diluent (not glucose), increase oxytocin
concentration to reduce fluid, and
restrict fluid intake by mouth; monitor
OXYTOCIN
Rx fluid, and electrolytes.

Inj.: 10 IU/mL, 1 mL ampul (IM, IV)
A synthetic nonapeptide identical with oxytocin
⎼ a peptide hormone secreted by the
posterior pituitary which participates in
labor or delivery and stimulates uterine
contraction.
Indications: Prevention and treatment of post-
partum and post-abortion hemorrhage;
induction and augmentation of labor.
Contraindications: Allergy to oxytocin or any
component of the formulation;
hypertonic uterine contractions,
mechanical obstruction to delivery, or
fetal distress; any condition where
spontaneous labor or vaginal delivery is
inadvisable; major cephalopelvic
disproportion.
Dose:
Prevention of postpartum hemorrhage, by IM
injection, ADULT and ADOLESCENT, 10
IU when the anterior shoulder is
delivered or immediately after birth.
Dose Adjustment:
Renal Impairment:
Use with caution (increased risk of water
retention and oxytocin accumulation)
Precautions:
Avoid prolonged administration in oxytocin-
resistant uterine inertia, in severe pre-
eclamptic toxemia, or severe
cardiovascular disease;
Previous uterine surgery, multiple pregnancies
or >4 previous births (increased risk of
uterine rupture); induction or
enhancement of labor in the presence of
borderline cephalopelvic disproportion
(avoid use if significant);
Mild-to-moderate pregnancy-associated
hypertension or cardiovascular disease;
age >35 years; history of low-uterine
segment caesarean section; caudal
block anesthesia (risk of severe
hypertension due to the enhanced
vasopressor effect of
sympathomimetics); avoid tumultuous
labor if fetal death or meconium-stained
amniotic fluid (risk of amniotic fluid
embolism) occurs; water intoxication

Page | 137
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
and hyponatremia (avoid large volume
infusions and restrict fluid intake).
Adverse Drug Reactions:
Less Common: Nausea, vomiting
Rare: Anaphylactoid reaction, arrhythmias,
ECG changes, flushing, prolonged QT
interval, rash, reflex tachycardia, severe
(tetanic) uterine spasm, and contraction
leading to uterine rupture or fetal
distress, hypoxia, and death; seizures,
transient hypotension, water
intoxication.
Drug Interactions:
Monitor closely with:
Ephedrine and epinephrine –may increase the
risk of hypertension due to their
enhanced vasopressor effect.
Administration: Administer IV bolus injection
slowly (avoid rapid injection due to risk
of cardiovascular effects). When using IV
infusion, monitor fluid balance to
prevent water intoxication.
Avoid large volume infusions and restrict fluid
intake to prevent water intoxication and
hyponatremia.
Pregnancy Category: X
ATC Code: H01BB02
THYROID and ANTITHYROID
PREPARATIONS
LEVOTHYROXINE
Rx
Oral: 50, 100, and 150 micrograms tablet (as
anhydrous sodium)
A synthetic thyroid form of thyroxine (T4), a
thyroid hormone involved in normal
metabolism, growth, and development.
It promotes gluconeogenesis, increases
utilization of glycogen stores, stimulates
the synthesis of proteins, and increases
Page | 138
basal metabolic rate. It is the
preparation of choice for replacement
therapy in treating primary and
secondary hypothyroidism.
Indication: Management of hypothyroidism of
any etiology; TSH suppression.
Contraindications: Hyperthyroidism from any
cause; acute MI; untreated subclinical
(suppressed serum TSH level with
normal T3 and T4 levels); overt
thyrotoxicosis of any etiology;
uncorrected adrenal insufficiency.
Dose:
Chronic hypothyroidism, by mouth, CHILD,
initially 25 micrograms daily, adjust by
25 micrograms every 2–4 weeks.
Congenital hypothyroidism, juvenile
myxedema, by mouth, NEONATE up to 1
month, initially 5-10 micrograms/kg
daily, (5 micrograms/kg daily in infants
and children >1 month), adjusted in
steps of 25 micrograms every 2-4
weeks, until mild toxic symptoms
appear, then reduce dose slightly.
Severe hypothyroidism, by mouth, ADULT,
initially 12.5–25 micrograms daily,
adjust by 25 micrograms every 2–4
weeks, as appropriate; CHILD, initially
25 micrograms daily, adjust by 25
micrograms every 2–4 weeks
Subclinical hypothyroidism, if treated, by
mouth, ADULT, 1 microgram/kg daily.
Hypothyroidism, by mouth, ADULT, the usual
dose is 1.6-1.7 micrograms/kg daily;
may give full dose right away if without
contraindications. For most, initially, 50-
100 micrograms daily (25-50
micrograms for those over 50 years)
before breakfast, increased by 25-50
micrograms every 3-4 weeks until
normal metabolism is maintained
(maintenance dose, 100-200
micrograms daily); in cardiac disease,
initially 25 micrograms daily or 50
micrograms on alternate days, adjusted
in steps of 25 micrograms every 4
weeks);
CHILD, the dose would depend on the
age:
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Daily Dose 12.5–25
Age
(microgram/kg) microgram
1-3 increments at 4- to
10-15
months 6-week intervals,
3-6 as needed.
8-10
months
6-12
6-8 TSH suppression in well-differentiated thyroid
months
1-5 years 5-6 cancer, papillary and follicular, by
6-12 years 4-5 mouth, ADULT, the dose is highly
>12 years 2-3 individualized; in general, more than 2
micrograms/kg daily may be needed to
suppress TSH to <0.1 mIU/L in
[NOTE: For infants 1-3 months at risk for
intermediate- to high-risk tumors; low-
developing cardiac failure, administer a
risk tumors may be maintained at 0.1–
lower starting dose of 25 micrograms
0.5 mIU/L.
daily. If the initial serum thyroxine is
TSH suppression in benign nodules and
below 5 micrograms/dL, begin
nontoxic
treatment at a higher dose of 50
multinodular goiter, by mouth, ADULT,
micrograms daily (12–17
initially 1.7–2 micrograms/kg daily may
micrograms/kg daily).];
be used with a target TSH of 0.1–0.3
mIU/L [NOTE: Routine use is not
Dosing for specific populations:
recommended. Avoid if TSH is already
suppressed].
Population Dose
Adults <50 years; 1.6–1.7
micrograms/kg Dose Adjustment:
daily; Elderly:
Introduce gradually to avoid sudden increase
Children in whom usually ≤200 in metabolic demands; maintenance
growth and puberty micrograms daily; replacement dose in the elderly may be
are complete; titrate dose every 6 less than in younger people.
weeks; The initial dose should not exceed 25-50
micrograms/day and should be
Adults >50 years may give full dose maintained at intervals of at least 4
recently treated for right away if weeks.
hyperthyroidism or without
who have been contraindications. Cardiovascular disorders (angina, heart
hypothyroid for only a failure, myocardial infarction or
few months insufficiency, hypertension):
Lower initial doses. Smaller increments and
Initially 25–50 longer intervals between increases could
micrograms daily, be necessary. A full replacement dose
Adults <50 years with adjust by 12.5–25 may not be appropriate. Use with caution
or without microgram and reduce the dose as needed.
cardiac increments at 6– to Long-standing Hypothyroidism:
disease 8-week intervals, Introduce gradually to avoid a sudden increase
as needed. in metabolic demands. Maintenance
replacement dose may be less than in
Initially 12.5–25 younger people
Adults >50 years with
micrograms daily,
cardiac disease Precautions:
then adjusted by

Page | 139
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
WARNING: Use with caution in patients with
underlying coronary artery disease,
previous MI, or acute coronary
syndromes and tachyarrhythmias.
Thyroid supplements are ineffective
and potentially toxic when used for the
treatment of obesity or for weight
reduction, especially in euthyroid
patients. High doses may produce
serious or even life-threatening toxic
ff i l l h d ih
Patients with cardiovascular disorders,
including angina, heart failure,
myocardial infarction or insufficiency,
and hypertension (lower initial doses,
smaller increments and longer intervals
between increases should be necessary;
full replacement dose may not be
appropriate).
Hypopituitarism or predisposition to adrenal
insufficiency (should be corrected with a
corticosteroid before treatment with
levothyroxine; otherwise, an acute
adrenal crisis, e.g., panhypopituitarism,
may be precipitated); elderly, long-
standing hypothyroidism (introduce
gradually to avoid any sudden increase
in metabolic demands).
Myxedema
Diabetes insipidus or diabetes mellitus (there
may be a need to increase the dose of
insulin or oral antidiabetic drug); may
occasionally precipitate or exacerbate a
pre-existing myasthenic syndrome.
Osteoporosis.
Benign thyroid nodules (treatment should
never be fully repressive).
Avoid use in postmenopausal women, men
more than 60 years of age, patients with
cardiovascular disease, osteoporosis, or
systemic illness, and patients with large
thyroid nodules or long-standing goiters,
or low-normal TSH levels).
Elderly.
Pregnancy (monitor thyroid function each
trimester; reassess thyroxine
maintenance dosage 6-8 weeks post-
partum; thyroxine may cross the
placenta and excessive dosage can be
detrimental to the fetus); breastfeeding
Page | 140
(the amount is small to affect tests for
neonatal hypothyroidism).
Adverse Drug Reactions:
Common: Anginal pain, excitability, flushing,
headache, muscular weakness,
restlessness, sweating, vomiting, weight
loss.
Less Common: Cramps, diarrhea, insomnia,
nervousness, palpitations, tachycardia.
Rare: Arrhythmias, decreased bone density (in
women), papilledema, seizures, tremors.
Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – enhanced
anticoagulant effect.
Combined Oral Contraceptives – the estrogen
component of COCs may alter thyroxine,
such that an increased dose is
necessary.
Phenobarbital – this accelerates the
metabolism of levothyroxine; may
increase its requirements in
hypothyroidism.
Phenytoin – this accelerates the metabolism of
levothyroxine; may increase its
requirements in hypothyroidism; the
plasma concentration of phenytoin is
possibly increased.
Rifampicin – this accelerates the metabolism
of levothyroxine; may increase its
requirements in hypothyroidism.
Theophylline – hypothyroid people may
metabolize theophylline more slowly
than euthyroid people.
Avoid concomitant use with:
Calcium salts – these decrease absorption of
thyroxine, possibly reducing its activity
(separate administration by at least 4
hours).
Ciprofloxacin – this may interfere with
absorption of thyroxine, resulting in
hypothyroidism (separate drug
administration times during a long
ciprofloxacin course).
Ferrous salts – these reduce thyroxine
absorption, possibly decreasing its
therapeutic effect (administer at least 4
hours apart).
Orlistat – this may decrease thyroxine
absorption, possibly resulting in
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
hypothyroidism (separate administration
by 4 hours).
Simethicone – when given regularly, this may
decrease thyroxine absorption, possibly
leading to hypothyroidism.
Administration: Should be taken on an empty
stomach; take on an empty stomach ½-
1 hour before meals, usually before
breakfast.
The tablet may be crushed and suspended in 5
to 10 mL water, however, this must be
used immediately.
Pregnancy Category: A
ATC Code: HO3AA01
METHIMAZOLE
Rx
Oral: 5 mg and 10 mg tablet
An imidazole-derived thioamide is used as an
antithyroid agent that inhibits the
synthesis of thyroid hormones by
blocking iodine oxidation in the thyroid
gland.
Indications: Treatment of hyperthyroidism; for
long-term use (given for 1-2 years) to
induce remission in small goiters;
hyperthyroidism associated with Graves’
disease
Contraindications: Previous agranulocytosis to
methimazole; known hypersensitivity to
methimazole or any component of the
formulation; drug-induced nephritis or
polyarteritis nodosa; liver disease; and
blood disorders, such as
granulocytopenia and aplastic anemia.
Dose:
Hyperthyroidism, by mouth, ADULT, initially 15
mg daily in 3 divided doses
(approximately every 8 hours) for mild
hyperthyroidism; 30-40 mg daily in
moderately severe hyperthyroidism; 60
mg/day in severe hyperthyroidism;
maintenance: 5-15 mg daily (given as a
single daily dose in many cases) – which
is continued for 12 to 18 months to
induce remission, or for 6 to 12 months
to prepare patients for definitive therapy
in the form of surgery or radioactive
iodine therapy; CHILD, initially 0.4
mg/kg/day in 3 divided doses,
maintenance: 0.2 mg/kg/day in 3
divided doses; suggested dosing based
on the age:
Daily dose
Population
(mg)
Infants 1.25
Children 1-5 years 2.5-5
Children 5-10 years 5-10
Children and Adolescents
10-20
10-18 years
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Hypothyroidism:
Adjust the dose to maintain a euthyroid state.
Monitor THS and free T4 levels.
Precautions:
Hypoprothrombinemia and bleeding; bone
marrow suppression (most severe
manifestation is agranulocytosis);
aplastic anemia; thrombocytopenia;
leukopenia (use with caution in patients
>40 years of age, with doses ≥40
mg/day); rash and urticaria (discontinue
in the presence of exfoliative dermatitis);
Discontinue if there are signs of infections
(e.g., fever, sore throat, mouth ulcer) and
clinical evidence of neutropenia; hepatic
necrosis, hepatitis, encephalopathy
(discontinue in the presence of hepatitis
– transaminase >3 times upper limit of
normal); leukocytoclastic vasculitis and
positive vasculitis (prompt
discontinuation is warranted in patients
who develop vasculitis during therapy);
lupus-like syndrome.
Page | 141
SYSTEMIC HORMONAL PREPARATIONS, EXCLUDING SEX HORMONES AND INSULIN
Pregnancy (first trimester: can cause fetal administration], Vitamin K Antagonists
harm; high risk of agranulocytosis if e.g. Warfarin (anticoagulant effect)
doses >40 mg/day).
Administration: May be taken with food or milk
Adverse Drug Reactions: to reduce stomach upset.
Common: Pruritus, rash.
Less Common: Abnormal loss of hair, Pregnancy Category: D
arthralgia, edema, epigastric distress, NOTE: Methimazole may actually be given in
headache, loss of taste, pregnancy if benefits outweigh risks
lymphadenopathy, myalgia, nausea,
neuritis, paresthesia, pigmentation, ATC Code: HO3BB02
pruritus, sialadenopathy, urticaria,
vertigo, vomiting.
Rare: Agranulocytosis, alopecia, aplastic
anemia, drug fever, granulocytopenia,
hepatitis, hypoprothrombinemia,
jaundice, lupus-like syndrome,
myopathy, nephritis, periarteritis,
thrombocytopenia.

Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – their activity
may be increased by methimazole
(because methimazole may potentially
inhibit vitamin K activity).
Beta-blockers – hyperthyroidism may cause an
increased clearance of beta-blockers;
may require adjustments according to
changes in thyroid status.
Cardiac Glycosides – their plasma
concentrations are increased by
methimazole.
Macrolide antibiotics – increased risk of QT
prolongation.
Prednisolone – its clearance is increased by
methimazole.
Theophylline – hyperthyroidism may cause a
decreased clearance of theophylline;
may require adjustments according to
changes in thyroid status.

Avoid concomitant use with:

Clozapine – increased risk of agranulocytosis.
Tizanidine - Increases serum concentration of
Tizanidine [initiate Tizanidine at 2 mg
and increase in 24 mg increments based
on patient response]
Reduces the therapeutic effect of the following
drugs:
BCG (Intravesical), Sodium Iodide I 131
[discontinue Methimazole 3–4 days
before Sodium Iodide I 131
Page | 142
ANTI-INFECTIVES
4.3. Drug factors such as:
ANTI-INFECTIVES • Antimicrobial spectrum and
(SYSTEMIC) antibacterial efficacy
(pharmacodynamics)
• Pharmacokinetics
ANTI INFECTIVES • Adverse effects
• Cost of therapy
(ORAL AND PARENTERAL)
• Stability at anticipated local
conditions, acceptability,
PRECEPTS TO BE CONSIDERED BEFORE ease and accuracy of dosing
STARTING THERAPY
Rules of Thumb:
1. Establish a presumptive diagnosis of
Some basic principles that should serve
bacterial infection and if possible, a specific
as guides to antimicrobial therapy:
etiologic diagnosis. Viral infections should
not be treated with antibiotics. There are
1. Choose the agent with:
few viral infections responsive to anti-viral
1.1. The narrowest spectrum which
therapy.
will cover the likely or proven
2. Samples of blood and/or body fluids and
pathogen(s);
discharges should be taken for gram-
1.2. The least expensive if efficacy
staining, and whenever possible,
and safety are otherwise equal;
submission of specimen to a higher
1.3. The lowest incidence of, or least
healthcare level for culture and sensitivity
serious, adverse reactions.
test.
2. Avoid the use of:
3. An up-to-date knowledge of prevalent
organisms and their current susceptibility is 2.1. Topical antimicrobials - topical
of great help in empirically choosing an antiseptics often suffice except
antibacterial drug before bacteriological for proven indications such as
confirmation is available. vaginitis, conjunctivitis and
impetigo;
4. The choice of a suitable antibiotic, the dose,
route and duration of therapy will depend 2.2. Antimicrobial combinations
on three factors: except in specific proven
circumstances (tuberculosis,
4.1. Suspected/proven causative
neonatal sepsis, etc.);
organism and its susceptibility
pattern 2.3. Prophylactic antibiotics, unless
4.2. Host/patient factors such as: they are proven to be of benefit
(e.g., post-exposure prophylaxis
• Age
meningococcemia and anthrax).
• Nature, severity and site of
infection aTurnidge J. Principles of Appropriate Prescribing of
• History of allergy and other Antimicrobials. Australian Journal of Hospital
concomitant diseases Pharmacy, 1994; 24:533-536
• Renal and hepatic functions
• Immunologic status
• Genetic factors
• Pregnancy and lactation

Page | 143
ANTI-INFECTIVES
ANTIBACTERIAL DRUG CLASSES
BETA- LACTAM, PENICILLINS
Penicillins with extended spectrum
The extended-spectrum penicillins are a group
of semi-
synthetic penicillin antibiotics that have a
wider spectrum of activity than natural
penicillins, penicillinase-resistant
penicillins, and aminopenicillins. They are
more active against gram-negative bacteria
because they are more resistant to
inactivation by extended-spectrum β-
lactamases and/or because they more
readily penetrate the outer membranes of
these gram-negative organisms.
Beta-lactamase sensitive penicillins
This class of antibiotics binds to penicillin
binding proteins that catalyzes the
synthesis of peptidoglycan and this leads to
the interruption of cell wall synthesis,
leading to bacterial cell growth inhibition
and cell lysis
Beta-lactamase resistant penicillins
These semisynthetic penicillins are indicated
for infection by β-lactamase-producing
staphylococci, although penicillin-
susceptible strains of streptococci and
pneumococci are also susceptible to these
agents. Listeria monocytogenes,
Enterococci, and methicillin- resistant
strains of Staphylococci are resistant.
Beta-lactamase inhibitors
Commonly used for empirical therapy against a
large
number of pathogens such as treatments
for aerobic and anaerobic infections. These
class of drugs are potent inhibitors of beta-
lactamases and protects hydrolysable
penicillins from inactivation.
Beta-lactamase inhibitors in combination
The β-lactamase inhibitors bind to β-
lactamases and
Page | 144
inactivate them. The β-lactamase inhibitors
lack direct antimicrobial activity but when
combined with an
antibiotic, they extend the spectrum of
activity and
increase stability against β-lactamases.
OTHER BETA-LACTAM ANTIBACTERIALS
Cephalosphorins (1st, 2nd, 3rd, 4th)
1st: First-generation cephalosporins
include cefazolin, cefadroxil, cephalexin,
cephalothin, cephapirin, and cephradine.
These drugs are very active against gram-
positive cocci.
2nd: Second-generation
cephalosporins include cefaclor,
cefamandole, cefonicid, cefuroxime,
cefprozil, loracarbef, and ceforanide; and
the structurally related cephamycins
cefoxitin, cefmetazole, and cefotetan,
which have activity against anaerobes.
3 :
rd Third-generation cephalosporins
include the: cefoperazone, cefotaxime,
ceftazidime, ceftizoxime, ceftriaxone,
cefixime, cefpodoxime proxetil, cefdinir,
cefditoren pivoxil, ceftibuten, and
moxalactam. They are active against
Citrobacter, S marcescens, and
Providencia.
4th: Cefepime belongs to the fourth-
generation cephalosporin. It is more
resistant to hydrolysis by chromosomal β
lactamases. Cefepime has good activity
against P aeruginosa,
Enterobacteriaceae, S. aureus, and S.
pneumoniae. It is highly active against
Haemophilus and Neisseria sp.
Monobactams
They have a narrow and characteristic
spectrum of activity which acts by
inhibiting bacterial cell wall synthesis due
to its high affinity for penicillin-binding
protein 3 (PBP-3) of gram-negative
bacteria. It is also active against most
Enterobacteriaceae (including E. coli,
Citrobacter, Enterobacter, Klebsiella,
Proteus, Providencia, Salmonella,
ANTI-INFECTIVES
Serratia, Shigella, Yersinia spp. and
Morganella morganii).
Carbapenems
Carbapenems have an extremely broad
spectrum of
antimicrobial activity and are highly
resistant to a variety of β-lactamases.
They bind to penicillin-binding proteins
and inhibit bacterial cell wall synthesis.
Tetracyclines
Tetracycline are broad-spectrum antibiotics
that inhibit
bacteriostatic action by reversibly binding
to the 30S subunits of the ribosome, thus
preventing protein synthesis and arresting
cell growth. They are active against many
gram-positive and gram-negative bacteria
including Chlamydiaceae, Mycoplasma
spp., Rickettsia spp., spirochetes, and
some protozoa.
Aminoglycosides
Aminoglycosides are used most widely in
combination with a β-lactam antibiotic in
serious infections with gram-negative
bacteria, in combination with vancomycin
or a β-lactam antibiotic for gram-positive
endocarditis, and for treatment of
tuberculosis. They are rapid bactericidal
irreversible inhibitors of protein synthesis
by binding on the 30S ribosome.
Lincosamides
Lincosamide is an antibiotic that binds to the
50S ribosomal subunit at a site closely
related to that at which macrolides act
resulting in bacteriostatic inhibition of
microbial protein synthesis.
Macrolides
Macrolides are bacteriostatic antibiotics with a
broad
spectrum of activity against many gram-
positive bacteria. The antimicrobial
activity of macrolides is exhibited by the
inhibition of bacterial protein biosynthesis
after binding of the macrolide, selectively
and reversibly, to the 50S ribosomal
subunit.
Chloramphenicol
Chloramphenicol is a potent inhibitor of
microbial protein synthesis by reversibly
binding to the 50S subunit of the bacterial
ribosome, thus preventing peptide bond
formation by peptidyl transferase. It has
both bacteriostatic and bactericidal action
against H. influenzae, N. meningitidis and
S. pneumoniae.
Quinolones
Quinolones are broad-spectrum antibacterial
agents. They act by blocking bacterial DNA
synthesis by inhibiting bacterial
topoisomerase II and topoisomerase IV.
Inhibition of topoisomerase II prevents the
relaxation of positively supercoiled DNA
while inhibition of topoisomerase IV
interferes with separation of replicated
chromosomal DNA.
Glycopeptide antibiotics
It is a narrow-spectrum antibiotic which affects
gram-
positive bacteria by interfering with the
incorporation of penicillin-binding protein
enzymes into the cell wall by binding to
precursors of cell wall synthesis.
Polymyxins
Polymyxins are bactericidal drugs that bind to
lipopolysaccharides (LPS) and
phospholipids in the outer cell membrane
of gram-negative bacteria. They
competitively displace divalent cations
from the phosphate groups of membrane
lipids, which leads to disruption of the
outer cell membrane, leakage of
intracellular contents, and bacterial
death.
Imidazole derivatives
These drugs inhibit the biosynthesis of
ergosterol, the
main sterol in membranes of fungi. These
agents also affect the synthesis of
Page | 145
ANTI-INFECTIVES
triglycerides and phospholipids leading to
an intracellular buildup of toxic
concentrations of hydrogen peroxide,
contributing to the deterioration of
subcellular organelles and to cell
necrosis.
Nitrofuran derivatives
Nitrofurans are bacteriostatic and bactericidal
for many
gram-negative and gram-positive
organisms but may not affect P.
aeruginosa and many strains of proteus.
Folic acid antagonists
Antifolate agents act at various steps in the
folic acid
cycle. Antifolate agents are most
commonly used in
combination to block sequential steps in
the folic acid metabolic pathway.
AMPHENICOLS
CHLORAMPHENICOL
Rx
Oral: 500 mg capsule
125 mg/5 mL suspension, 60 mL (as
palmitate)
A potent, broad-spectrum, microbial protein
synthesis inhibitor (50S subunit), which
is active against most gram-negative and
gram-positive bacteria; it is associated
with serious hematological side-effects
when given systemically, and should
therefore be reserved for the treatment
of life-threatening infections.
Indications: Uncomplicated typhoid fever (2nd
line treatment).
NOTE: It is associated with serious hematological side-
effects when given systemically and should
therefore be reserved for the treatment of life-
threatening infections.
Contraindications: Treatment of trivial or viral
infections; bacterial prophylaxis; known
hypersensitivity to chloramphenicol or
Page | 146
any component of the formulation; acute
porphyria; anemia or thrombocytopenia;
neonates <1 week and premature
infants; pregnancy (third trimester:
neonatal “grey” syndrome), and
breastfeeding.
Dose:
Uncomplicated typhoid fever, by mouth, CHILD,
50-75 mg/kg in divided doses every 6
hours daily for 14-21 days; ADULT, 1 g
given every 6 hours for 14 days.
NOTE: Plasma concentration monitoring is required in
neonates; and monitoring is preferred in those
<4 years of age, in the elderly, and in hepatic
impairment.
Dose Adjustments:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist (due to dose-
related depression of hematopoiesis).
Use with caution; monitor serum
concentrations.
Children with immature metabolic processes:
A dose of 25 mg/kg/day will usually produce
therapeutic chloramphenicol
concentration in the blood; the serum
drug concentration should be monitored
by microbiological techniques wherever
possible.
Precautions:
WARNING: Serious and fatal blood
dyscrasias, including anemia,
thrombocytopenia and granulocytopenia,
have occurred after short-term and
prolonged therapy. Monitor CBC
frequently in all patients. Use only in
serious infections.
Typhoid (Jarisch-Herxheimer reaction may
occur at start of treatment); avoid
repeated courses and prolonged use;
severe renal and hepatic impairment;
breastfeeding (the concentration in milk
is usually insufficient to cause “grey”
syndrome; but, use alternative drug if
possible; may cause bone marrow
ANTI-INFECTIVES
toxicity in infants); G6PD deficiency
(hemolysis may occur).
Adverse Drug Reactions:
Common: Headache, nausea, reversible bone
marrow suppression, vomiting.
Less Common: C. difficile-associated disease,
dryness of mouth, confusion, diarrhea,
glossitis, mild depression, stomatitis.
Rare: Anaphylaxis, aplastic anemia, “grey”
syndrome (abdominal distension, ashen
grey skin, circulatory collapse, cyanosis,
greenish diarrhea); hypersensitivity
reactions, hypothermia, leukopenia,
optic neuritis, peripheral neuropathy,
thrombocytopenia.
Drug Interactions:
NOTE: Chloramphenicol inhibits liver microsomal
enzymes (CYP2C9), and may affect
concentration of drugs which are metabolized
by the enzyme (see Appendix).
Monitor closely with:
Anticoagulants (e.g., warfarin) – their
anticoagulant effect can be enhanced by
chloramphenicol.
Phenobarbital – this increases the metabolism
of chloramphenicol, thereby reducing its
concentration and antibacterial activity.
Phenytoin – chloramphenicol impairs its
metabolism, thereby increasing its
concentration and risk of toxicity.
Avoid concomitant use with:
Bactericidal antibiotics – chloramphenicol
(bacteriostatic) can antagonize the
bactericidal action of penicillins and
aminoglycosides.
Iron – chloramphenicol increases serum
concentration of iron, and induces bone
marrow toxicity (if myelosuppression
occurs, monitor iron stores and
decrease iron as needed).
Rifampicin – this accelerates the metabolism
of chloramphenicol, thereby decreasing
its plasma concentration.
Administration: Take on an empty stomach 1
hour before, or 2 hours, after meals.
Pregnancy Category: C
BETA-LACTAMS
TETRACYCLINES
DOXYCYCLINE
Rx
Oral: 100 mg capsule (as hyclate)
A broad-spectrum and long-acting tetracycline
antibiotic that is used for infections
caused by chlamydia, spirochetes and
other pathogens, and for malarial
prophylaxis.
Indications: Treatment of leptospirosis;
juvenile
periodontitis; gastroenteritis from Vibrio
cholera; acute bacterial exacerbation of
chronic bronchitis (ABECB); blepharitis
with associated acne rosacea;
chlamydia and mycoplasma infections;
second-line treatment of acute bacterial
rhinosinusitis (ABRS) or for patients with
severe penicillin allergy; pneumonia due
to Burkholderia pseudomallei.
Contraindications: Known hypersensitivity to
tetracyclines or any component of the
formulation; should not be given to
children <8 years of age (deposition of
tetracyclines in growing bones and
teeth, causing deformation and
inhibiting bone growth); pregnancy (first
trimester: effects on skeletal
development in animal studies; 2nd and
3 rd trimesters: dental discoloration;
maternal hepatotoxicity with large
doses); breastfeeding; porphyria; SLE.
Dose:
Acute bacterial exacerbation of chronic
bronchitis (ABECB), mild-to-moderate, by
mouth, ADULT, 100 mg twice daily
Acute bacterial rhinosinusitis (ABRS), by
mouth, ADULT, 100 mg every 12 hours
for 5-7 days.
Blepharitis with associated acne rosacea, by
mouth, ADULT, 100 mg twice daily for 2
weeks, then every 24 hours
Chlamydia infections, by mouth, ADULT, 100
mg twice daily for 7 days.
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ANTI-INFECTIVES
Early syphilis, by mouth, ADULT, 100 mg twice
daily for 14 days; late latent syphilis, 100
mg twice daily for 28 days.
Gastroenteritis due to Vibrio cholera in adults,
by mouth, ADULT, 300 mg x 1 dose.
Juvenile periodontitis, by mouth, CHILD ≥8
years, 200 mg daily for 7 days.
Leptospirosisa:
Clinical manifestations that should lead a
health practitioner to consider
suspected leptospirosis:
1. any individual with acute febrile
illness of at least 2 days duration;
2. AND residing in a flooded area or
has high-risk exposure (defined as
wading in floods and
contaminated water, contact with
animal fluids, swimming in flood
water or ingestion of
contaminated water, with or
without cuts or wounds);
3. AND with at least 2 of the following
symptoms: myalgia, calf
tenderness, conjunctival
suffusion, chills, abdominal pain,
headache, jaundice, oliguria.
•For mild leptospirosis (defined as acute
febrile illness and various
manifestations BUT with stable vital
signs, anicteric sclera, good urine output
and NO evidence of meningismus /
meningeal irritation, sepsis / septic
shock, difficulty of breathing and
jaundice that can be managed at the
out-patient setting with close
monitoring) use doxycycline as first line
agent to be started as soon as the
diagnosis is suspected, regardless of the
phase of the disease or duration of
symptoms, by mouth, for 7 days, ADULT,
100 mg twice daily; CHILD > 8 years old,
2-4 mg/kg in 2 divided doses, not to
exceed 200 mg/day. (For alternative
antibiotic treatment, see under
Amoxicillin).
•For moderate to severe leptospirosis,
refer immediately to a higher level of
healthcare facility or the hospital.
Patients present with unstable vital
signs, jaundice/ icteric sclerae,
abdominal pain, nausea, vomiting and
diarrhea, oliguria/anuria, meningismus/
meningeal irritation, sepsis/ septic
shock, altered mental status, difficulty of
breathing, hemoptysis
•For pre-exposure prophylaxis:
ONLY for individuals who intend to visit
highly endemic areas and are likely to
get exposed (e.g., travelers, soldiers,
those engaged in water-related
recreational and occupational activities
in highly endemic areas), for short term
exposures, by mouth, for ADULT MALES
and NON-PREGNANT, NON-LACTATING
FEMALES, 4 mg/kg x 1 dose (maximum:
200 mg) once weekly to begin 1-2 days
before exposure and continued
throughout the period of exposure.
Currently, there is NO recommended pre-
exposure prophylaxis that is safe for
pregnant or lactating women.
May take 100 mg 2x a day if 200 mg
single dose is not tolerated.
•For post-exposure prophylaxis:
a. In Low-Risk Exposure:
defined as single history of wading
in flood or contaminated water
and the absence of wounds, cuts,
or open lesions of the skin, give
doxycycline by mouth, ADULT, 200
mg within 24-72 hours from
exposure.
b. In Moderate-Risk Exposure:
defined as single history of wading
in flood or contaminated water
and the presence of wounds, cuts,
or open lesion in the skin, OR, the
accidental ingestion of
contaminated water, give
doxycycline by mouth, ADULT, 200
mg once daily for 3-5 days to be
started immediately within 24-72
hours from exposure.
c. In High-Risk Exposure:
defined as continuous exposure –
more than a single exposure or
several days exposure – of wading
in flood or contaminated water
with or without the presence of
wounds, cuts, or open lesions of
the skin; swimming in flooded

Page | 148
ANTI-INFECTIVES
waters especially in areas infested
with domestic/sewer rats and
ingestion of contaminated water,
give doxycycline by mouth, ADULT,
200 mg once weekly until the end
of the exposure.
d. For Pediatric Patients:
by mouth, CHILD, > 8 years old, 4
mg/kg as single dose (maximum,
200 mg); and if child is exposed
for more than 7 days, repeat the
dose after one week.
NOTE: Antibiotic prophylaxis in the prevention of
leptospirosis is NOT 100% effective. Protective
measures should still be used. The most
effective preventive measure remains to be
avoidance of high-risk exposure. If unavoidable,
use protective measures such as boots,
goggles, overalls, or rubber gloves.
NOTE: There is currently NO recommended pre-
exposure and post-exposure prophylaxis for
leptospirosis that is safe for pregnant or
lactating women (see Warning)..
Mycoplasma infections, by mouth, ADULT, 100
mg twice a day for 5 – 10 days
Pelvic inflammatory disease, by mouth, ADULT,
100 mg twice daily for 14 days.
Pneumonia due to Burkholderia pseudomallei,
by mouth, ADULT, 100 mg twice daily
CHILD, 4 mg/kg divided twice daily with
Trimethoprim-Sulfamethoxazole
Suspected uncomplicated genital chlamydia
and non-gonococcal urethritis, by mouth,
ADULT, 100 mg twice daily for 1-3 weeks
depending on the site and severity of the
infection.
a The Philippine Clinical Practice Guidelines on the Diagnosis,
Treatment and Prevention of Leptospirosis in Adults 2010,
PSMID, Quezon City.
Dose Adjustments:
Renal Impairment:
Doxycycline can be used without dose
adjustment (does not lead to excessive
accumulation when used at the usual
recommended doses).
Hepatic Impairment:
Avoid high doses (hepatotoxicity more likely to
occur in hepatic impairment).
Precautions:
WARNING:
• There is currently NO recommended pre-
exposure and post-exposure prophylaxis that is
safe for pregnant or lactating women. Do not
administer to pregnant women.
• Avoid use in children less than 8 years of age.
Tetracyclines may increase muscle weakness
in patients with myasthenia gravis and
may exacerbate SLE; overgrowth of non-
susceptible organisms (including fungi);
hepatic impairment; photosensitivity
(avoid exposure to sunlight or
sunlamps); intracranial hypertension;
tissue hyperpigmentation; breastfeeding
(use other alternative drugs if possible);
probable absorption and discoloration of
teeth in infants may usually be
prevented by chelation with calcium
from milk.
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea, enamel
dysplasia, epigastric burning, headache,
nausea, photosensitivity, reduced bone
growth (in children <8 years), tooth
discoloration, vaginitis, vomiting.
Less Common: Anorexia, bone deformity,
dental hypoplasia, flushing, fungal
overgrowth, rash, stomatitis.
Rare: Allergic reactions including Stevens-
Johnson syndrome and anaphylaxis;
benign intracranial hypertension, blood
disorders, C. difficile-associated disease,
esophageal ulcers, hepatitis,
hepatotoxicity, nail discoloration,
pancreatitis, serum sickness-like
reactions, toxic epidermal necrolysis,
visual disturbances, tinnitus.
Drug Interactions:
Monitor closely with:
Contraceptives, Oral – their efficacy may be
reduced by doxycycline.
Rifampicin – this may increase the metabolism
of doxycycline, thereby reducing its
efficacy.
Avoid concomitant use:
Antacids (e.g., aluminum and magnesium
hydroxide) – these form poorly-soluble
Page | 149
ANTI-INFECTIVES
chelates with doxycycline, thus reducing
its absorption and anti-infective capacity
(separate administration by at least 2
hours).
Calcium – this forms poorly-soluble chelates
with doxycycline, thus reducing its
absorption and anti-infective capacity
(separate administration by at least 2
hours).
Ferric Salts – these form poorly-soluble
chelates with doxycycline, thus reducing
its absorption and anti-infective capacity
(separate administration by as long as
possible, at least 2 hours); doxycycline
also significantly reduce iron absorption.
Magnesium – this forms poorly-soluble
chelates with doxycycline, thus reducing
its absorption and anti-infective capacity
(separate administration by at least 2
hours).
Oral Retinoids (e.g., isotretinoin, acitretin) –
may increase the risk of benign
intracranial hypertension.
Penicillins – being bacteriostatic, doxycycline
may interfere with the bactericidal action
of penicillins.
Zinc Salts – these form poorly-soluble chelates
with doxycycline, thus reducing its
absorption and anti-infective capacity
(separate administration by at least 2
hours).
Administration: To be taken with food or after
a meal. Capsules should be swallowed
whole with plenty of fluid (a full glass of
water); remain sitting or standing (for at
least ½ hour) to prevent esophageal
irritation or damage; it may be given with
food to counter gastric irritation. Do not
give with milk.
Pregnancy Category: D
Page | 150
PENICILLINS
AMOXICILLIN
Rx
Oral: 250 mg and 500 mg capsule (as
trihydrate)
100 mg/mL granules/powder for drops
(suspension), 15 mL (as trihydrate)
250 mg/5 mL granules/powder for
suspension, 60 mL (as trihydrate)
A penicillinase-susceptible aminopenicillin
having extended spectrum of activity;
oral absorption is not impaired by food,
and is more rapidly and completely
absorbed, with higher bioavailability and
less GI irritation than ampicillin.
Indications: Upper and lower respiratory tract
infections (including low-risk community-
acquired pneumonia) due to susceptible
bacteria; exacerbations of chronic
bronchitis; bacterial otitis media;
uncomplicated enteric or typhoid fever;
prophylaxis of bacterial endocarditis
during dental surgery; Helicobacter
pylori eradication (as combination
therapy - see under Clarithromycin for
the Eradication of H. pylori Infection in
Peptic Ulcer Disease); as alternative
antibiotic for mild leptospirosis.
Antimicrobial Resistance ALERT!
Amoxicillin should not be used for the
empiric treatment of Acute
Uncomplicated Cystitis and Acute
Uncomplicated Pyelonephritis due to the
relatively poor efficacy and very high
prevalence of antimicrobial resistance.
Contraindication: Known hypersensitivity to
penicillins, or any component of the
formulation.
Dose:
Acute bacterial exacerbation of chronic
bronchitis (ABECB), mild moderate
infections, by mouth, ADULT, 500 mg
thrice a day for 5-10 days.
Acute otitis media, with no antibiotic use in the
prior month, by mouth, CHILD <2 years
old, 80-90 mg/kg/day in divided doses
ANTI-INFECTIVES
every 12 hours for 10 days; CHILD 2-5
years old, 80-90 mg/kg/day in divided
doses every 12 hours for 7 days; , CHILD
>5 years old, 80-90 mg/kg/day in
divided doses every 12 hours for 5-7
days; ADULT, 1g every 8 hours for 10
days.
Community Acquired Pneumonia, Low-risk
(CAP-LR) in adults, without co-morbid
illness, by mouth, ADULT, 1g thrice a day
for 5-7 days.
(See the chapter on updated Interim
Practice Guidelines on CAP).
Community Acquired Pneumonia, pediatric,
PCAP A or PCAP B (non-severe), due to a
bacterial pathogen, in cases where
antibiotics were not previously given,
and regardless of immunization status
against Haemophilus influenzae type B
or to Streptococcus pneumoniae, by
mouth, amoxicillin trihydrate may be
given at 40-50 mg/kg/day, (maximum:
1,500 mg per day), in 3 divided doses for
5 – 7 days. Based on the Updated
Guidelines for the Management of PCAP
A or PCAP B.
(See the chapter on the updated Interim
Practice Guidelines for the Management
of Pediatric CAP for more details).
Endocarditis prophylaxis prior to dental
procedure, by mouth, ADULT, 2 g single
dose 1 hour before procedure; CHILD,
50 mg/kg (maximum, 2 g) single dose
30-60 minutes before procedure.
Enteric or typhoid fever (uncomplicated), as 1st
line treatment, by mouth, CHILD and
INFANT, 75-100 mg/kg divided every 8
hours daily for 14 days; ADULT, 1 gram
every 6 hours for 14 days
Exudative or diffuse erythematous tonsillitis, by
mouth, CHILD, 50 mg/kg/day in divided
doses every 8-12 hours (maximum: 1
gram/day) for 10 days; ADULT, 500 mg
every 12 hours for 10 days.
Leptospirosis, mild, by mouth, CHILD, as 1st
line treatment for a child < 8 years old,
50 mg/kg every 8 hours for 7 days
(maximum: 500 mg every 8 hours);
ADULT (as alternative treatment), 500
mg every 6 hours or 1 g every 8 hours for
7 days.
Pre-exposure prophylaxis for
leptospirosis, by mouth, 50 mg/kg/day
in divided doses given every 8 hours for
3-5 days (maximum daily dose: 500 mg
every 8 hours).
The Philippine Clinical Practice Guidelines in the
Diagnosis, Treatment and Prevention of
Leptospirosis in Adults, 2010, PSMID, Quezon
City.
Dose Adjustment:
Renal Impairment:
Patients with impaired renal function do not
generally require dose reduction unless
impairment is severe, in which case, the
patient should be referred to a specialist.
Use of certain dosage forms (i.e. ER 775 mg
tablet and IR 875 mg tablet) should be
avoided in patients with CrCl <30
mL/minute or patients requiring
hemodialysis.
CrCl 10-30 mL/minute: 250-500 mg every 12
hours.
CrCl <10 mL/minute: 250-500 mg every 24
hours.
NOTE: Moderately dialyzable (20% to 50%) by
hemodialysis or peritoneal dialysis;
approximately 50 mg of amoxicillin per
liter of filtrate is removed by continuous
arteriovenous or venovenous
hemofiltration.
Precautions:
WARNING: Serious and occasionally severe or
fatal hypersensitivity reactions have been
reported in patients on penicillin therapy.
History of allergy to penicillins; renal
impairment (risk of crystalluria with high
doses; dosage adjustment
recommended); high incidence of
erythematous rash in glandular fever,
acute lymphoblastic leukemia,
infectious mononucleosis, chronic
lymphocytic leukemia, CMV infection,
HIV infection; risk of crystalluria
(maintain adequate hydration with high
doses); superinfection (prolonged use
may result in fungal or bacterial
superinfection, including C. difficile-
associated diarrhea or CDAD and
pseudomembranous colitis).
Page | 151
ANTI-INFECTIVES
Pregnancy (not known to be harmful);
breastfeeding (monitor infant; trace
amounts found in milk, but appropriate
to use).
Adverse Drug Reactions:
Common: Diarrhea, headache, nausea.
Less Common: Abdominal pain, antibiotic-
associated colitis, vomiting.
Rare: Allergic reactions including anaphylaxis,
angioneurotic edema, CNS disorders,
including convulsions (associated with
high doses, or impaired renal function);
coagulation disorders, hemolytic
anemia, interstitial nephritis,
mucocutaneous candidiasis,
neutropenia, pustular drug eruption,
rash, serum sickness-like reactions,
thrombocytopenia, urticaria.
NOTE: A widespread, erythematous maculopapular
rash (pseudoallergic) is common; often occurs
after >7 days treatment and resolves 1-7 days
after treatment is stopped, or after 6-14 days if
it continues (although not immune-mediated,
consider skin testing to check for
hypersensitivity before using penicillin again).
Drug Interactions:
Monitor closely with:
Allopurinol – when combined with amoxicillin,
there is increased risk of rash
occurrence.
Contraceptives, Oral – their efficacy may be
reduced by amoxicillin.
Tetracyclines (e.g., doxycycline, minocycline,
and tetracycline) and Fusidic acid –
these could reduce the therapeutic and
pharmacologic action of amoxicillin.
Vitamin K antagonists (e.g., warfarin) –
penicillins may enhance the
anticoagulant effect of these drugs.
BCG and Typhoid vaccine- Amoxicillin may
reduce the therapeutic effect of these
vaccines
Avoid concomitant use with:
Chloramphenicol – this may decrease the
effects of amoxicillin.
Administration: May be taken with or without
food (may be given without regard to
meals); best taken at the start of meals
for better absorption, and reduction of GI
discomfort. Administer around-the-clock
to promote less variation in peak and
Page | 152
trough serum levels. Appropriate amount
of suspension may be mixed with
formula, milk, fruit juice, water, ginger
ale, or cold drinks; administer dose
immediately after mixing.
Pregnancy Category: B
AMPICILLIN
Rx
Inj.: 250 mg, 500 mg and 1 g vial (IM, IV) (as
sodium salt)
An extended-spectrum aminopenicillin useful
for treating serious conditions not
amenable to oral therapy, or infections
caused by penicillin-susceptible
bacteria, such as anaerobes,
enterococci, and beta lactamase-
negative strains of gram-negative cocci
and bacilli. This is given parenterally
because only less than half of the oral
dose is absorbed (absorption is further
decreased by food).
Indications: For use in health facilities with
BeMonc units as treatment for Potential
Neonatal Sepsis (with gentamicin).
NOTE:
Potential sepsis in the neonate is considered
in:
Asymptomatic infant < 28 days old, with
documented maternal risk factors such
as history of UTI during the last trimester,
membranes ruptured > 18 hours before
delivery, fever > 38⁰C before delivery or
during labor and/ or presence of foul
smelling or purulent amniotic fluid.
Antimicrobial Resistance ALERT!
Due to high resistance of Haemophilus
pneumoniae to ampicillin, this antibiotic
is not recommended as empiric therapy
for infections caused by this pathogen.
Contraindications: Known hypersensitivity to
penicillins or any component of the
formulation; patients with glandular
fever or acute lymphatic leukemia.
ANTI-INFECTIVES
Dose: CrCl >50 mL/minute: Administer every 6 hours.
Potential neonatal sepsis, by IV infusion, CrCl 10-50 mL/minute: Administer every 6-12
Ampicillin PLUS (Gentamicin or hours.
Amikacin) CrCl <10 mL/minute: Administer every 12-24
(Source: National Antibiotics Guidelines hours.
2019):
Precautions for Ampicillin:
For Ampicillin: WARNING: Serious and occasionally severe
Gestational Postnatal Ampicillin or fatal
Age (Weeks) Days 25–50 hypersensitivity reactions have been
mg/kg reported in patients on penicillin
<29 0-28 Give q 12 therapy, especially with history of beta-
days hrs IV lactam hypersensitivity, history of
>28 days Give q 8 sensitivity to multiple allergens, or
hrs previous IgE-mediated reactions. Use
37 - 44 0-7 days Give q 12 with caution in asthmatic patients.
hrs
>7 days Give q 8 In patients with history of allergy; renal
hrs impairment (if severe, refer to a
>45 For all Give q 6 specialist); high incidence of
ages hrs erythematous rash in glandular fever,
infectious mononucleosis, chronic
For Gentamicin: lymphocytic leukemia, acute
Gestational Post- Gentamicin lymphoblastic leukemia, CMV infection,
Age natal HIV infection.
Days Appearance of a rash should be carefully
<29 weeks 0-7 5mg/kg evaluated to differentiate a non-allergic
q48 hrs ampicillin rash from a hypersensitivity
reaction; rash occurs in 5% to 10% of
8-28 4mg/kg children and is a generalized dull red,
q36 hrs; maculopapular rash, generally
appearing 3-14 days after the start of
>29 4mg/kg therapy. It normally begins on the trunk
q24 hrs and spreads over most of the body. It
30-34 0-7 •4.5mg/kg may be most intense at pressure areas,
weeks q36 hrs elbows and knees;
>8 • 4 mg/kg Prolonged use may result in fungal or bacterial
q24 hrs superinfection, including C. difficile-
>35 weeks 0-7 • 4mg/kg associated diarrhea (CDAD) and
q24 hrs pseudomembranous colitis;
>8 • 4mg/kg Use with caution in patients with renal
q24 hrs impairment
(dosage adjustment recommended);
In elderly patients, particularly those with
RECONSTITUTION AND ADMINISTRATION.
concomitant cardiac diseases especially
According to manufacturer’s directions.
arrhythmias;
Pregnancy (not known to be harmful);
Dose Adjustment for Ampicillin:
breastfeeding (trace amounts in milk,
Renal Impairment:
but appropriate to use; monitor infant).
For mild-to-moderate renal impairment, dose
NOTE: Rash (hypersensitivity or toxic response)
reduction or dose interval extension is
may be indicative of a serious reaction
warranted; for severe impairment, the
(discontinue treatment if it occurs).
patient should be referred to a specialist.
Page | 153
ANTI-INFECTIVES
Adverse Drug Reactions from Ampicillin:
Common: Diarrhea, increased transaminase
levels, nausea, pain at the site of
injection, pruritus, rash, urticaria,
vomiting.
Less Common: Coagulation disorders,
erythema multiforme, GI upset,
hemolytic anemia, interstitial nephritis,
leukopenia, serum sickness-like
reactions, thrombocytopenia, toxic
epidermal necrolysis.
Rare: Anaphylaxis, angioedema, antibiotic-
associated colitis, crystalluria,
electrolyte imbalance, pustular drug
eruption.
Drug Interactions with Ampicillin:
Monitor closely with:
Allopurinol – when combined with ampicillin,
there is increased risk of rash
occurrence.
Aminoglycosides (e.g., amikacin, gentamicin) –
these may be rendered inactive by
ampicillin.
Anticoagulants (e.g., warfarin) – their bleeding
risks may be increased by ampicillin (due
to possible prolongation of bleeding
time).
Contraceptives, Oral – their efficacy may be
reduced by ampicillin; there may also be
an increased risk of breakthrough
bleeding.
Fusidic acid and Tetracycline derivatives –
these drugs reduce the therapeutic
effect of ampicillin
Heparin – the risk of bleeding may be
increased by ampicillin.
BCG and Typhoid Vaccine (affects only the live
attenuated Ty21a strain)- Ampicillin may
reduce the therapeutic effect of these
vaccines
Avoid concomitant use with:
Atenolol – its antihypertensive and anti-anginal
effects may be impaired by ampicillin.
Chloramphenicol – this may decrease the
effects of ampicillin.
Administration of Ampicillin: Administer
around-the-clock to promote less
variation in peak and trough serum
levels. Administer over 3-5 minutes
Page | 154
(125-50 mg) or over 10-15 minutes (1-
2g).
Use freshly prepared solutions. IV and IM
solutions should be used within 1 hour
after preparation.
Do not exceed a rate of 100 mg/minute; More
rapid infusions may cause seizures.
Ampicillin and gentamicin should not be mixed
in the same IV tubing.
Pregnancy Category of Ampicillin: B
ATC Code:
(See under Gentamicin for dose adjustment,
adverse drug reactions, drug
interactions and other details regarding
gentamicin and amikacin).
PENICILLIN G BENZATHINE
Rx (Benzathine
benzylpenicillin)
Inj.: 1,200,000 units vial (MR) (IM)
A beta lactamase-sensitive penicillin having a
similar spectrum of activity with
penicillin G crystalline; but provides a
tissue depot from which the drug is
slowly absorbed over a period of 12
hours to several days.
NOTE: Peak plasma concentrations are
reached within 13-24 hours; detectable
in the urine for 3-4 weeks.
Indications: Streptococcal
pharyngitis/tonsillitis; rheumatic fever
prophylaxis; syphilis.
Contraindications: Known hypersensitivity to
penicillins or any component of the
formulation; neurosyphilis; intravascular
injection.
Dose:
Pharyngitis or tonsillitis from Group A, C, G
streptococcal infection, by deep IM
injection, ADULT, as 2nd line treatment,
1.2 million units as a single dose.
ANTI-INFECTIVES
Rheumatic fever prophylaxis, by deep IM
injection, CHILD ≤27 kg, 600,000 units
every 3 weeks; CHILD >27 kg and
ADULT, 1.2 million units every 3 weeks.
For high-risk patients, every 3 weeks, for
at least 10 years (For the Duration of
Secondary Rheumatic Fever (RF)
Prophylaxis, see table under
Phenoxymethylpenicillin or Penicillin V).
Syphilis, primary, by deep IM injection, CHILD,
50,000 U/kg x 1 dose (maximum: 2.4
MU); ADULT, as 1st line treatment, 2.4
million units as a single dose, divided
between 2 sites.
Syphilis, secondary, by deep IM injection,
CHILD, 50,000 U/kg x 1 dose
(maximum: 2.4 million units); ADULT, as
1st line treatment, 2.4 million units x 1
dose.
Syphilis, early latent, by deep IM injection,
CHILD, 50,000 U/kg x 1 dose
(maximum: 2.4 million units); ADULT, as
1st line treatment, 2.4 million units x 1
dose.
Syphilis, late latent, by deep IM injection,
CHILD, 50,000 U/kg x 1 dose up to adult
dose of 2.4 million units, administered
as 3 doses at 1 week intervals (total
150,000 units/kg up to the adult dose of
7.2 MU); ADULT, as 1st line treatment,
7.2 million units total dose,
administered as 3 doses of 2.4 MU IM on
each buttock at 1 week intervals.
Syphilis, tertiary, by IM injection, ADULT, 7.2
million units administered as 3 doses of
2.4 MU IM each at 1 week interval.
Syphilis, congenital, possible, less likely and
unlikely, by IM injection, see the
following table on treatment of
congenital syphilis.
(Source: National Antibiotic Guidelines
2019).
Treatment of Congenital Syphilis:
Proven Aqueous Crystalline Penicillin G
or Highly 100,000–150,000 U/kg/day,
Probable administered as 50,000 U/kg/dose
IV
q 12 hours during the first 7 days of
life
and q 8hours thereafter for a total of
10 – 15 days, OR, Procaine
Penicillin G
50,000 U/ kg/dose x 1 dose for
10-15d
Possible Aqueous Crystalline Penicillin G
100,000–150,000 U/kg/d,
administered as
50,000 U/kg/ dose IV q 12 hours
during the first 7days of life & q 8
hours thereafter for total 10
days, OR, Procaine Penicillin G
50,000 U/ kg/dose IM x 1 dose for
10 days,
OR, Benzathine Penicillin G
50,000 U/kg IM x 1 dose
Less Benzathine penicillin G 50,000
likely units/kg
IM x 1 dose, OR, Do not treat but
do close
serologic follow-up every 2–3
months
for 6 months for infants whose
mother’s
nontreponemal titers decreased at
least
fourfold after appropriate therapy
for early syphilis or remained stable
for low-titer, latent syphilis
(e.g., VDRL <1:2; RPR <1:4).
Unlikely No treatment is required, but
infants with
reactive nontreponemal tests
should be
followed serologically to ensure the
nontreponemal test returns to
negative.
Benzathine penicillin G 50,000
U/kg
as a single IM injection might be
considered, particularly if follow-up
is
uncertain and the neonate has a
reactive nontreponemal test.
Page | 155
ANTI-INFECTIVES
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
Dose Adjustment:
Geriatric:
Refer to adult dosing.
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING:
Not for IV use.
Do not inject IV or admix with other IV
solutions Reports of inadvertent IV
administration are associated with
cardiorespiratory arrest and death.
Prior to administration, carefully read the
warnings, adverse reactions, and
dosage and administration sections
of the labeling.
Serious and occasionally severe or fatal
hypersensitivity reactions have been
reported in patients on penicillin
therapy, especially a history of beta-
lactam hypersensitivity, history of
sensitivity to multiple allergens, or
previous IgE-mediated reactions (Use
with caution in asthmatic patients);
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-
associated diarrhea (CDAD) and
pseudomembranous colitis.
History of allergy to penicillins; renal failure
Neurotoxicity: high doses may cause
convulsions; Pregnancy (not known to be
harmful), breastfeeding (trace amounts in
milk; safe in usual dosage; monitor infant).
Adverse Drug Reactions:
Common: Pain and sterile inflammation at
injection site.
Less Common: Diarrhea.
Rare: CNS toxicity, convulsions, hemolytic
anemia, hypersensitivity reactions,
including anaphylaxis; interstitial
nephritis, Jarisch-Herxheimer reaction,
Page | 156
neutropenia, non-allergic (embolic-toxic)
reactions, thrombocytopenia.
Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – penicillins may
enhance their anticoagulant effect.
BCG and Typhoid vaccine- Benzathine
benzylpenicillin may reduce the
therapeutic effect of these vaccines
Contraceptives, Oral – their efficacy may be
reduced by benzathine benzylpenicillin.
Fusidic acid - may reduce the therapeutic
effect of benzathine benzylpenicillin.
Avoid concomitant use with:
Probenecid – this may increase the serum
concentration of penicillins.
Tetracycline – this may antagonize the
bactericidal effect of benzathine
benzylpenicillin.
Administration: Warm to room temperature
before administration to lessen the pain
associated with injection.
Administer by deep IM injection only in the
upper, outer quadrant of the buttock; in
children <2 years of age, IM injections
should be made into the mid-lateral
muscle of the thigh, not the gluteal
region. Do not inject near an artery or a
nerve; permanent neurological damage
or gangrene may result; avoid major
nerves and blood vessels as severe
neurovascular damage may occur. Give
doses >900 mg as 2 injections at
separate sites. When doses are
repeated, rotate the injection site. Do
NOT administer by IV, SC, or intra-
arterially.
Pregnancy Category: B
ANTI-INFECTIVES
PENICILLIN G
Rx CRYSTALLINE
(Benzylpenicillin)
Inj.: 1,000,000 and 5,000,000 units (IM, IV)
(as sodium or potassium salt)
A beta lactamase-sensitive penicillin that is
given by injection for infections caused
by Streptococci, Neisseria,
actinomycetes, spirochetes, and some
anaerobes.
NOTE: Peak plasma concentrations are
reached within 15-30 minutes.
Indications: Syphilis, congenital, (See
Congenital Syphilis under Penicillin G
Benzathine).
NOTE: This is also indicated for more serious
infections, such as streptococcal
endocarditis, meningococcal meningitis
and septicemia, osteomyelitis, cellulitis,
congenital syphilis, gas gangrene and
leptospirosis for which treatment is
instituted in the hospital.
Contraindications: Known hypersensitivity to
penicillins or any component of the
formulation; avoid intrathecal route.
Dose:
Syphylis, congenital, possible and proven or
highly probable (See Treatment for
Congenital Syphylis under Penicillin G
Benzathine).
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
IV route is preferred for neonates and
infants; doses over 1.2 g should be given
by the IV route only.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Uremic patients with CrCl >10
mL/minute/1.73m2:
Administer full loading dose followed by
½ of the loading dose given every 4-5
hours.
CrCl <10 mL/minute/1.73m2: Administer full
loading dose followed by ½ of the
loading dose given every 8-10 hours.
Intermittent hemodialysis (IHD) (administer
after
hemodialysis on dialysis days):
Administer normal loading dose followed
by either 25% to 50% of normal dose
every 4-6 hours or 50% to 100% of
normal dose every 8-12 hours. For mild-
to-moderate infections, administer 0.5-1
MU every 4-6 hours or 1-2 MU every 8-
12 hours. For neurosyphilis,
endocarditis, or serious infections,
administer up to 2 MU every 4-6 hours;
administer after dialysis on dialysis days
or supplement with 500,000 units after
dialysis. [Note: Dosing dependent on the
assumption of 3 times/week, complete
IHD sessions.
Continuous renal replacement therapy (CRRT):
Drug clearance is highly dependent on
the method of renal replacement, filter
type, and flow rate. Appropriate dosing
requires close monitoring of
pharmacologic response, signs of
adverse reactions due to drug relation to
target trough (if appropriate). The
following are general recommendations
only (based on dialysate
flow/ultrafiltration rates of 1-2 L/hour
and minimal residual renal function) and
should not supersede clinical judgment.
CVVH: Loading dose of 4 MU, followed by
2 MU every 4-6 hours.
CVVHD: Loading dose of 4 MU, followed
by 2-3 MU every 4-6 hours.
CVVHDF: Loading dose of 4 MU, followed
by 2-4 MU every 4-6 hours.
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ANTI-INFECTIVES
Precautions:
WARNING: Serious and occasionally severe
or fatal hypersensitivity reactions have
been reported in patients on penicillin
therapy, especially with a history of beta-
lactam hypersensitivity, history of
sensitivity to multiple allergens, or
previous IgE-mediated reactions. Use
with caution in asthmatic patients.
History of allergy to penicillins;
Renal failure (maximum, 6 g daily;
neurotoxicity – high doses may cause
cerebral irritation, convulsions, or
coma); sodium restriction, heart failure
(contains approximately 78 mg Na per
1.2 g); false-positive urinary glucose (if
tested for reducing substances).
Avoid intra- -arterial administration or injection
into or near major peripheral nerves or
blood vessels; Prolonged use may result
in fungal or bacterial superinfection,
including C. difficile-associated diarrhea
(CDAD) and pseudomembranous colitis.
Pregnancy (not known to be harmful),
breastfeeding (trace amounts found in
milk; safe in usual dosage; monitor
infant); syphilis (Jarisch-Herxheimer
reaction can occur after starting
treatment).
Adverse Drug Reactions:
Common: Pain and sterile inflammation at
injection site, phlebitis.
Less Common: Antibiotic-associated colitis,
diarrhea, glossitis, nausea, stomatitis,
vomiting.
Rare: CNS toxicity, electrolyte disturbances,
hemolytic anemia, hypersensitivity
reactions including anaphylaxis;
interstitial nephritis, Jarisch-Herxheimer
reaction, neutropenia, non-allergic
(embolic-toxic) reaction,
thrombocytopenia.
Drug Interaction:
Monitor closely with:
Anticoagulants (e.g., warfarin) – penicillins may
enhance their anticoagulant effect.
BCG and Typhoid vaccine 9affects only the live
attenuated Ty21a strain)-
Page | 158
Benzylpenicillin reduces the effect of
these vaccines
Contraceptives, Oral – their efficacy may be
reduced by benzylpenicillin.
Fusidic acid- May reduce the therapeutic effect
of benzylpenicillin
Avoid concomitant use with:
Probenecid – this may increase the serum
concentration of penicillins.
Tetracycline – this may antagonize the
bactericidal effect of benzylpenicillin.
Administration:
For IM: Administer IM by deep injection in the
upper outer quadrant of the buttock.
For Intermittent IV: May be dissolved in small
amounts of SQFI, NS, D5W and
administered peripherally as a 50,000-
100,000 units/mL solution. In fluid-
restricted patients, 146,000 units/mL in
SQ results in a maximum recommended
osmolality for peripheral infusion.
Infused over 15-30 minutes.
For Continuous IV infusion: Determine the
volume of fluid and rate of its
administration required by the patient in
a 24-hour period. Add the appropriate
daily dosage of penicillin to this fluid.
Reconstituted solutions should be inspected
visually; only clear solutions, free of
visible particles, should be used. Freshly-
prepared solutions for injection or
infusion should be used immediately.
Pregnancy Category: B
PHENOXYMETHYL
Rx PENICILLIN (Penicillin V)
Oral: 250 mg and 500 mg tablet/capsule
(as potassium salt)
250 mg/5 mL granules/powder for
syrup/ suspension, 60 mL (as
potassium salt)
A beta lactamase-sensitive penicillin having a
similar antimicrobial action and
spectrum of activity with Penicillin G
ANTI-INFECTIVES
crystalline; but is less active and is inflammation, decrease the fever, and
suitable for oral administration. keep cardiac failure in check.

Indications: Streptococcal pharyngitis or Duration of Secondary Rheumatic Fever

tonsillitis; mouth infections; S. pyogenes (RF) Prophylaxis Category:
tonsillitis; primary and secondary Clinical or
prophylaxis of rheumatic fever; acute Echocar- Duration
gingivitis, acute necrotizing ulcerative diographic
gingivitis, pericoronitis, and erysipelas. Findings
RF w/ carditis & 10 years or until
Contraindications: Known hypersensitivity to residual heart 40 years of age
penicillins or any component of the disease (whichever is
formulation; serious infections; (persistent longer)
infectious mononucleosis; should not be valvular
used for meningococcal and gonococcal disease)
infections. RF w/ carditis 10 years or until
Dose: but no residual 21 years of age
Acute gingivitis, by mouth, ADULT, 500mg heart disease (whichever is
every 4 hours with metronidazole (no valvular longer)
500mg every 8 hours disease)
Acute necrotizing ulcerative gingivitis, by RF without 5 years or until
mouth, ADULT, 500mg every 6 hours carditis 21 years of age
with metronidazole 500mg every 8 (whichever is
hours longer)
Pericoronitis, by mouth, ADULT, 500mg every 6
hours for 7days. (Source: National Antibiotics Guidelines,
Presumed S. pyogenes tonsillitis or 2019).
pharyngitis, by mouth, ADULT and CHILD
>10 years old, 500 mg twice daily for 10 Streptococcal pharyngitis or tonsillitis due to
days; CHILD <10 years old, 250 mg group A, C, G streptococci, by mouth,
twice daily for 10 days. CHILD, as 1st line treatment, 25-50
Recurrent pharyngitis, by mouth, as 1st line mg/kg in divided doses every 6 hours
treatment, CHILD, 25-50mg/kg in daily x 10 days. ADULT, as 1st line
divided doses every 6 hours for 10 days; treatment, 500 mg every 12 hours or
ADULT, 500mg every 12 hours or 250mg 250 mg every 6 hours x 10 days.
every 6 hours for 10 days.
Rheumatic fever, primary prophylaxis, by Dose Adjustments:
mouth, ADULT, 500 mg 2-3 times daily Geriatric:
for 10 days; CHILD, 250 mg 2-3 times Refer to adult dosing.
daily for 10 days.
(See following note on acute rheumatic Renal and Hepatic Impairment:
fever therapy). For mild-to-moderate impairment, dose
Rheumatic fever, secondary prophylaxis, reduction, or extension of dose interval
alternative to Benzathine Penicillin G, by may be warranted; for severe
mouth, ADULT, 500 mg twice daily; impairment, the patient should be
CHILD 1-5 years, 125 mg twice daily; referred to a specialist.
CHILD 6-12 years, 250 mg twice daily. CrCl 10-50mL/minute: Administer every 8-12
hours.
NOTE: CrCl <10mL/minute: Administer every 12-16
Acute Rheumatic Fever therapy is hours.
symptomatic to control the

Page | 159
ANTI-INFECTIVES
Precautions: Tetracycline – this may antagonize the
WARNING: Serious and occasionally severe or fatal bactericidal effect of
hypersensitivity reactions have been reported in phenoxymethylpenicillin.
patients on penicillin therapy, especially with a
history of beta-lactam hypersensitivity, history of Administration: Should be taken on an empty
sensitivity to multiple allergens, or previous IgE- stomach to increase oral absorption,
mediated reactions. and at least 30 minutes before, or 2
Use with caution in asthmatic patients.
hours after, food.
History of allergy to penicillins; renal and Pregnancy Category: B
hepatic impairment; pregnancy (not
known to be harmful); breastfeeding
(trace amounts in milk, but safe in usual BETA-LACTAMASE RESISTANT
dosage; monitor infant regularly). PENICILLINS
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-
associated diarrhea (CDAD) and
CLOXACILLIN
pseudomembranous colitis; Rx
Use with caution in patients with severe renal
impairment (dosage adjustment
necessary); Oral: 500 mg capsule (as sodium salt)
Use with caution in patients with a history of 250 mg/5 mL powder for oral solution,
seizure disorder; high levels, particularly 60 mL
in the presence of renal impairment,
may increase risk of seizures. A penicillinase-resistant, isoxazolyl penicillin
having high potency against
Adverse Drug Reactions: staphylococci, which are resistant to
Common: Black hairy tongue, mild diarrhea, benzylpenicillin.
epigastric distress, nausea, vomiting,
oral candidiasis.
Less Common: Fever.
Rare: Acute interstitial nephritis; convulsions; Indications:
hemolytic anemia, hypersensitivity In children: as first-line treatment of
reactions (anaphylaxis); leukopenia; methicillin-sensitive Staphylococcus
positive Coombs reaction; seizure; and, aureus (MSSA) and methicillin-resistant
thrombocytopenia. S. aureus (MRSA) skin abscess, boils
Drug Interaction: and furuncles; as first-line treatment of
Monitor closely with: folliculitis with large, multiple lesions;
Anticoagulants (e.g., warfarin) – penicillins may Staphylococcal Scalded Skin Syndrome
enhance their anticoagulant effect. where pathogen may be MSSA or MRSA.
BCG and Typhoid vaccine- In adults: as second-line treatment in adults of
Phenoxymethylpenicillin may reduce the documented methicillin-sensitive S.
effect of these vaccines aureus (MSSA) skin abscess, boils and
Contraceptives, Oral – their efficacy may be furuncles; for suspected S. aureus acute
reduced by phenoxymethylpenicillin. bacterial skin and skin structure
Fusidic acid – may reduce the therapeutic infection (ABSSSI) where there is
effect of phenoxymethylpenicillin fluctuance or positive Gram stain; otitis
externa; pyomyositis; for documented
Avoid concomitant use with: MSSA purulent cellulitis.
Probenecid – this may increase the serum
concentration of penicillins. Antimicrobial Resistance ALERT!
Due to the high prevalence of methicillin
resistant Staphylococcus aureus

Page | 160
ANTI-INFECTIVES
(MRSA), cloxacillin should not be used
for empiric treatment of moderate to
severe infections suspected to be
secondary to S. aureus. (See section on
MRSA under Clindamycin for further
information).
Contraindication: Known hypersensitivity to
penicillins or any component of the
formulation.
Dose:
As first-line treatment in children of methicillin-
sensitive Staphylococcus aureus (MSSA)
and methicillin-resistant S. aureus
(MRSA), by mouth, CHILD, 50-100
mg/kg/day in 4 doses (maximum 2
g/day) for 5-10 days (See Interim
Practice Guidelines on Common
Bacterial Skin Infections and National
Antibiotics Guidelines).
As first-line treatment in children of folliculitis
with large, multiple lesions, by mouth,
CHILD, 50-100mg/ kg/day in 4 doses
(maximum 2 g/day) for 7-10 days (See
Interim Practice Guidelines on Common
Bacterial Skin Infections and National
Antibiotics Guidelines).
Staphylococcal Scalded Skin Syndrome in
children where pathogen may be MSSA
or MRSA, as 1st-line treatment, by mouth,
CHILD, 50-100 mg/kg/ day (maximum 2
g/day) in 4 doses for 7-10 days for MSSA
(See Interim Practice Guidelines on
Common Bacterial Skin Infections and
National Antibiotics Guidelines).
As second-line out-patient treatment for adults
with the documented methicillin-
sensitive Staphylococcus aureus (MSSA)
skin abscess, boils and furuncles, by
mouth, after incision and drainage,
ADULT, 500 mg 4x a day for 5 to 10 days
(See Interim Practice Guidelines on
Common Bacterial Skin Infections and
National Antibiotics Guidelines).
For suspected S. aureus acute bacterial skin
and skin structure infection (ABSSSI) in
adults where there is fluctuance or
positive Gram stain, out-patient
treatment, by mouth, ADULT, 500 mg 4x
a day for 7 to 10 days (See Interim
Practice Guidelines on Common
Bacterial Skin Infections and National
Antibiotics Guidelines).
For documented MSSA purulent cellulitis, by
mouth, ADULT, 500 mg 4x a day
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
Dose Adjustments:
Geriatric:
Refer to adult dosing.
Renal and Hepatic Impairment:
Same dosage as in patients with normal
function may be used in patients with
mild-to-moderate impairment; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: Serious and occasionally severe
or fatal hypersensitivity reactions have
been reported in patients on penicillin
therapy, especially with a history of beta-
lactam hypersensitivity, history of
sensitivity to multiple allergens, or
previous IgE-mediated reactions. Use
with caution in asthmatic patients.
History of allergy to penicillins (if skin rash
develops, the patient should be
prescribed a different class of
antimicrobial); heart failure; renal
impairment; hepatic impairment
(cholestatic jaundice may occur up to
several weeks after the treatment has
been stopped; administration for more
than two weeks and increasing age are
risk factors).
Penicillin use has been associated with
hematologic disorders believed to be a
hypersensitivity phenomenon. Reactions
are most often reversible upon
discontinuing therapy.
Pregnancy (not known to be harmful);
breastfeeding (trace amounts found in
milk, but safe in usual dosage; monitor
infant).
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea,
flatulence, nausea.
Page | 161
ANTI-INFECTIVES
Less Common: Fever, hypersensitivity
reactions, including joint pain, rash and
urticaria; sore tongue and mouth.
Rare: Agranulocytosis, antibiotic-associated
colitis, blood in stools, black hairy
tongue, cholestatic jaundice, electrolyte
disturbances, hemolytic anemia,
hepatitis, interstitial nephritis,
neutropenia, renal failure,
thrombocytopenia, serum sickness-like
reactions.
Drug Interactions:
Monitor closely with:
BCG and Typhoid vaccine (affects only the live
attenuated Ty21a strain)- Cloxacillin may
reduce the therapeutic effect of these
vaccines.
Contraceptives, Oral – their efficacy may be
reduced by cloxacillin.
Fusidic acid and tetracycline derivatives- may
reduce the therapeutic effect of these
vaccines.
Methotrexate – cloxacillin may increase serum
concentration of methotrexate and risk
of toxicity.
Mycophenolate – cloxacillin may decrease the
serum concentration of mycophenolate
and its active metabolites.
Probenecid – this decreases cloxacillin
excretion, and prolongs its activity
(through competitive renal tubule
secretion).
Avoid concomitant use with:
Bacteriostatic antibiotics (e.g., tetracycline,
chloramphenicol) – these may
antagonize the activity of cloxacillin.
Administration: Should be taken on an empty
stomach 1 hour before, or 2 hours, after
meals (intake of food further reduces its
absorption).
Pregnancy Category: B
Page | 162
OXACILLIN
Rx
Inj.: 250 mg and 500 mg (as sodium salt),
vial (IM, IV)
Indications: For use in the health facilities with
BeMonc units for the treatment of
Neonatal Sepsis.
Contraindications: Hypersensitivity to oxacillin,
any penicillin or any component of the
formulation.
Dose:
Neonatal sepsis, by IM injection or IV push,
together with IV Ceftriaxone – See
section on Ceftriaxone for dosing details.
Dose Adjustment:
For geriatric patients.
Precautions:
WARNING: Serious and occasionally
severe or fatal hypersensitivity
reactions have been reported in
patients on penicillin therapy, especially
with a history of beta-lactam
hypersensitivity, history of sensitivity to
multiple allergens, or previous IgE-
mediated reactions. Use with caution in
asthmatic patients.
Monitor patients for
anaphylactic/hypersensitivity reactions,
hepatitis, superinfection; Use with
caution in patients with renal
impairment; Use with caution in special
population: Elderly; Neonates.
Adverse Drug Reactions:
Fever, rash, diarrhea nausea and vomiting,
agranulocytosis, eosinophilia,
leukopenia, neutropenia,
thrombocytopenia, hepatotoxicity, acute
interstitial nephritis, hematuria, serum
sickness like reactions
ANTI-INFECTIVES
Drug Interactions:
Reduces therapeutic effect of the following
drugs:
BCG, Typhoid vaccine (Only the live
attenuated Ty21a strain is affected.)
Reduces therapeutic effect of Oxacillin:
Fusidic acid, Tetracycline derivatives
Decreases excretion of the following drugs:
Methotrexate
Decreases serum concentration of the
following drugs:
Mycophenolate
Increases serum concentration of Oxacillin:
Probenecid
Administration:
For IM: Administer into muscle; avoid sciatic
nerve injury.
For IV: Administer around-the-clock to promote
less variation in peak and trough serum
levels. Admin IV push over 10 minutes.
Administer IV piggyback over 30
minutes.
Pregnancy Category: B
ATC Code: J01CF04
PENICILLINS + Beta-Lactamase
Inhibitors in Combination (BLIC)
CO-AMOXICLAV (Amoxicillin
Rx + Potassium Clavulanate)
Oral: 500 mg amoxicillin (as trihydrate) +
125 mg potassium clavulanate per
tablet
875 mg amoxicillin (as trihydrate) +
125 mg potassium clavulanate per
tablet
200 mg amoxicillin (as trihydrate) +
28.5 mg potassium clavulanate per
5 mL granules/powder for
suspension, 70 mL
400 mg amoxicillin (as trihydrate) + 57
mg potassium clavulanate per 5 mL
granules/powder for suspension, 70
mL
600 mg amoxicillin (as trihydrate) + 42.9
mg potassium clavulanate per 5 mL
granules/ powder for suspension
A combination of an extended-spectrum
aminopenicillin and a beta-lactamase
inhibitor, which has increased
antibacterial activity against amoxicillin-
resistant and beta-lactamase-producing
strains of bacteria.
Indications: Infections due to beta-lactamase-
producing bacteria and where
amoxicillin alone is not appropriate,
including respiratory tract infections
such as low-risk CAP (CAP-LR) in patients
with co-morbid illness or with recent
antibiotic therapy where Gram-negative
bacilli can coexist; otitis media and
sinusitis due to susceptible
microorganisms; treatment for Acute
Uncomplicated Pyelonephritis where
Gram stain shows Gram-positive
organisms; asymptomatic bacteriuria;
alternative treatment in Acute
Uncomplicated Cystitis and Acute
Uncomplicated Pyelonephritis (in non-
pregnant women); animal bites; severe
dental infections with spreading cellulitis
or those not responding to first-line
antibiotics; exudative or diffuse
erythematous, recurrent pharyngitis,
acute bacterial rhinosinusitis (ABRS),
acute otitis media as second line
treatment in adults, acute otitis media in
children due to resistant S. pneumoniae
where child shows clinical failure after 3
days of initial therapy, severe dental
infections..
Contraindications: Known hypersensitivity to
amoxicillin, clavulanic acid or penicillins;
history of penicillin- or amoxicillin with
clavulanic acid-associated cholestatic
jaundice or hepatic dysfunction.
Dose:
Acute bacterial rhinosinusitis, by mouth,
CHILD, 45 – 50 mg/kg/day every 12
hours for 10-14 days. ADULT, 1gram
Page | 163
ANTI-INFECTIVES
(high dose amoxicillin) 3x a day for 10 –
14 days.
NOTE: Antibiotics for bacterial sinusitis
are given if: 1) with high fever and
purulent nasal discharge or facial pain
for >3 days; 2) still symptomatic after 10
days with no antibiotics; or, 3) symptoms
worsen after a typical viral illness that
lasted 5 days and had initially improved.
Acute otitis media, by mouth, ADULT, second
line treatment, with no penicillin allergy,
875/125 mg every 12 hours for 10 days.
Acute otitis media in children due to resistant
S. pneumoniae where child shows
clinical failure after 3 days of initial
therapy (see definition below), by mouth,
CHILD > 3 months and <40 kg (first line
treatment), 90 mg/kg per day divided
every 12 hours using 600/42.9 mg for
10 days (<2 years old) and for 5-7 days
(> 2 years old).
NOTE: Definition of clinical failure:
No change in ear pain, fever, bulging
tympanic membrane, or otorrhea, after 3
days of initial therapy.
Acute uncomplicated cystitis, alternative
treatment, by mouth, ADULT, 625 mg
twice daily for 7 days. See Clinical
Practice Guidelines – UTI for further
information
Acute uncomplicated pyelonephritis due to
gram-positive organisms only , by mouth,
ADULT, 625 mg thrice daily for 14 days.
See Clinical Practice Guidelines – UTI for
further information.
Asymptomatic bacteriuria, by mouth, ADULT, in
non-pregnant patients, 625 mg twice
daily for 7-14 days; in pregnant women,
625 mg twice daily for 7 days. See
Clinical Practice Guidelines – UTI for
further information
Bite wounds, cat, dog and human (mild to
moderate infections), by mouth, 7:1
formulation: 25-45 mg/kg/day in 2
doses (amoxicillin component)
(maximum of 1.75 g/day), OR 4:1
formulation: 20-40 mg/kg/day in 3
doses (amoxicillin component)
(maximum 1.5 g/day).
Buccal cellulitis, by mouth, CHILD as second-
line treatment, <5 years old, 45 mg/kg
Page | 164
per day divided every 12 hours for 7-14
days
Community-Acquired Pneumonia, Pediatric,
non-severe, (PCAP A or B) if with no Hib
vaccination or incomplete or unknown
vaccination history, by mouth, INFANT
and CHILD up to 5 years old, 80-90
mg/kg per day (amoxicillin component)
divided every 8 hours (4:1 preparations),
or divided every 12 hours (7:1
preparations), CHILD >40 kg, 500/125
mg every 8 hours (Max 2 g/day of
amoxicillin)
Community-Acquired Pneumonia, low-risk
(CAP-LR) with coexisting gram-negative
bacilli, by mouth, ADULT, 625 mg thrice
a day or 1 g twice a day for 5-7 days. See
Interim Practice Guidelines – CAP for
further information.
Periodontal abscess, by mouth, 45 mg/kg/day
(amoxicillin component) divided into 2
doses for 7 days.
Recurrent pharyngitis, by mouth, CHILD, as
second line treatment, for 3 months and
older and <40 kg: 20-40 mg/kg divided
every 8 hours daily (amoxicillin
component) for 10 days; for 3 months
and older and >40 kg: 500 mg/125 mg
every 12 hours for 10 days. ADULT, 500
mg/125 mg every 12 hours for 10 days;
Severe dental infections, by mouth, ADULT,
375 mg every 8 hours for 5 days.
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
NOTE: Patients with dysphagia – may
substitute 250 mg/5 mL suspension for
625 mg tablet; and 200 mg/5 mL or 400
mg/5 mL suspension for 1 g tablet.
Dose Adjustments:
Renal and Hepatic Impairment (except for
Contraindications stated above):
For mild-to-moderate impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Note: 875 mg tablet is not recommended for
patients with renal impairment. The
extended-release formulation is
ANTI-INFECTIVES
contraindicated in patients with a CrCl of
30mL/min.
Adult and pediatric patients weighing more
than 40 kg:
CrCl 30 mL/min or more: No dosage
adjustment necessary.
CrCl 10-30 mL/min 250 to 500 mg
(amoxicillin component) every 12 hours,
depending on the severity of the
infection.
CrCl less than 10 mL/min 250-500 mg
(amoxicillin component) every 24 hours,
depending on the severity of the disease.
Pediatric patients: dose adjustments are
based on a usual dose of 20-40 mg/kg
per day (amoxicillin component) divided
every 8 hours, 25-45 mg/kg per day
(amoxicillin component) divided every
12 hours.
CrCl 10-29 mL/min/1.73 m2: 8-20
mg/kg/dose amoxicillin component (20
mg/kg/dose for high dose) every 12
hours.
CrCl less than 10 ml/min/1.73 m2: 8-20
mg/kg/dose amoxicillin component (20
mg/kg/dose for high dose) every 24
hours.
Precautions:
Due to differing content of clavulanic acid, not
all products are interchangeable.
History of allergy to penicillins; renal
impairment (risk of crystalluria with high
doses; maintain adequate hydration);
hepatic impairment (monitor liver
function; duration of treatment should
not exceed 14 days since cholestatic
jaundice has been reported during, or
shortly after, the treatment; it is more
common in patients over the age of 65
years and in males); erythematous rash
(common in glandular fever, CMV
infection); chronic lymphatic leukemia;
and possibly HIV infection.
Patients with infectious mononucleosis may
develop rash with this product;
Pregnancy (not known to be harmful);
breastfeeding (trace amounts in milk).
Adverse Drug Reactions:
Common: Diarrhea.
Less Common: abdominal distress,
candidiasis, cholestatic jaundice, diaper
rash, dizziness, flatulence, headache,
hepatic insufficiency, loose stool,
mycosis, nausea, skin rash, superficial
staining of teeth (with suspension),
urticaria, vaginal mycosis, vaginitis,
vasculitis (hypersensitivity), vomiting.
Rare: Abdominal discomfort, agranulocytosis,
anaphylaxis, angioedema, cholestatic
jaundice, convulsions, elevation of
ALT/AST, erythema multiforme,
exfoliative dermatitis, hemolytic anemia,
hepatitis, hepatotoxicity, hypersensitivity
reactions, leukopenia (reversible),
neutropenia (reversible),
pseudomembranous colitis, rash, serum
sickness-type reactions, Stevens-
Johnson syndrome, thrombocy- topenia,
toxic epidermal necrolysis, vasculitis
Drug Interactions:
Monitor closely with:
Allopurinol – when combined with co-
amoxiclav, there is increased risk of rash
occurrence.
Contraceptives, Oral – their efficacy may be
reduced by co-amoxiclav.
Warfarin- incompatible with co-amoxiclav; may
have unpredictable effects
Administration: Dosage depends on age,
weight and renal function of the patient
and the severity of infection. Dosages
are expressed in terms of co-amoxiclav
content except when doses are stated in
terms of an individual component.
Therapy can be started parenterally and
continued with an oral preparation.
Administer at the start of a meal (to
minimize potential GI intolerance, and
optimize absorption).
NOTE: Two 500 mg amoxicillin/125 mg
clavulanate tablets should not be taken
at one time since the double dose of
clavulanate is more likely to cause GI
tract adverse effects. Two co-amoxicalv
250/125 mg tablets should not be
substituted for one co-amoviclav
500/125 mg tablet since they are not
equivalent.
Page | 165
ANTI-INFECTIVES
Pregnancy Category: B
CEPHALOSPORINS
CEFALEXIN
Rx (CEPHALEXIN)
Oral: 500 mg capsule (as monohydrate)
100 mg/mL, granules/powder for drops (as
monohydrate), 10 mL
125 mg/5 mL granules/powder for
syrup/suspension (as monohydrate), 30
mL
250 mg/5 mL granules/powder for
syrup/suspension (as monohydrate), 60
mL
A first-generation cephalosporin that is
intended for oral administration because
it is almost completely absorbed from
the GI tract; it is active against gram-
positive cocci, such as pneumococci,
streptococci and staphylococci, but is
less active than the other first-
generation cephalosporins against
penicillinase-producing staphy- lococci.
Indications: Mild methicillin sensitive
Staphylococcus aureus (MSSA) skin
abscess, boils or furuncles as second-
line treatment; and dental prophylaxis.
Restricted for asymptomatic bacteriuria
and acute uncomplicated cystitis in
pregnancy only for urine isolates
susceptible to cefalexin as
demonstrated on urine culture and
sensitivity.
Antimicrobial Resistance ALERT!
Due to increasing resistance to
cefalexin, its use in UTI is confined to
asymptomatic bacteriuria and acute
cystitis in pregnancy where isolates are
shown to be susceptible to it.
Contraindications: Known hypersensitivity to
cefalexin and any cephalosporins, or any
component of the formulation;
previously experienced major allergy to
penicillins.
Page | 166
Dose:
Asymptomatic bacteriuria in pregnancy for
susceptible organisms demonstrated on
urine c/s, by mouth, ADULT, 500 mg
twice daily for 7 days. See Clinical
Practice Guidelines – UTI for further
information.
Acute uncomplicated cystitis in pregnancy for
susceptible organisms demonstrated on
urine c/s, by mouth, ADULT, 500 mg 4
times daily for 7 days. See Clinical
Practice Guidelines – UTI for further
information
Dental prophylaxis, in patients allergic to
penicillins or ampicillin, by mouth,
CHILD, 50 mg/kg; ADULT, 2 g.
Methicillin-sensitive Staphylococcus aureus
(MSSA), as documented cause of skin
abscess, boil, furuncle, by mouth, CHILD,
as 1st line treatment: in mild-moderate
infection, 25- 50 mg/kg/day divided in 3-
4 doses; in severe infections, 75-100
mg/kg/day divided into 3- 4 doses per
day (maximum: 4 g/ day) for 5-10 days.
ADULT, as 2nd line treatment, 500 mg 3-
4 x a day, for 5-10 days. (See Interim
Interim Practice Guidelines for Common
Bacterial Skin Infections).
Dose Adjustments:
Renal Impairment:
Dosage should be reduced.
Adult: CrCl 10-50mL/min, 500 mg every 8-12
hours; CrCl < 10 mL/min, 250-
500 mg every 12-24 hours
Hemodialysis patients: 250 mg every 12-24
hours;
moderately dialyzable (20-50%);
give dose after dialysis session.
Precautions:
Elevated INR especially with nutritionally-
deficient patients, prolonged treatment,
hepatic or renal disease;
In patients allergic to penicillins (there is partial
cross-allergenicity of penicillins and
cephalosporins; if an allergic reaction
occurs, the drug should be
discontinued); marked renal impairment
(increases the risk of nephrotoxicity and
neurotoxicity – seizures or coma – with
ANTI-INFECTIVES
high doses); patients should be
monitored carefully so that any side
effects or unusual manifestations of
drug idiosyncrasy may be detected;
elevated INR (may be associated with
increased INR, especially in nutritionally-
deficient patients, those with prolonged
treatment, hepatic or renal disease);
Prolonged use may result in the overgrowth of
non-susceptible organisms, or fungal or
bacterial superinfections; in individuals
with a history of GI disease, particularly
colitis (possible risk of antibiotic-
associated pseudomembranous colitis).
Pregnancy (not known to be harmful);
breastfeeding (present in milk in low
concentrations, but appropriate to use;
may cause loose bowel actions in child).
may prolong and/or worsen the
condition.
Zinc salts – these may decrease the absorption
of cefalexin.
Administration: Administer without regard to
food. If with GI distress, take with food.
Give around-the-clock to promote less
variation in peak and trough serum
levels.
Pregnancy Category: B
CEFIXIME
Rx

Adverse Drug Reactions: Oral: 200 mg capsule

Common: Abdominal pain, allergy, C. difficile- 20 mg/mL granules for drops
associated disease, dizziness, diarrhea, (suspension),
headache, hypersensitivity, increased 10 mL
transaminases, rash. 100 mg/5 mL granules for suspension,
Less Common or Rare: Anemia, cholestatic 60 mL
hepatitis, erythema multiforme, nausea,
neutropenia, Stevens-Johnson An orally-active, third-generation
syndrome, toxic epidermal necrolysis, cephalosporin that has greater activity
vomiting. against gram-negative bacteria;
possesses longer duration of action than
Drug Interactions: the other orally-active cephalosporins.
Monitor closely with:
Metformin, Probenecid – serum Indications: Uncomplicated anogenital
concentrations may be increased by gonorrhea of the cervix, urethras, rectum
cefalexin. and conjunctiva- for use only when
Vitamin K Antagonists (e.g., warfarin) – ceftriaxone is unavailable; second-line
cephalosporins may enhance their therapy for uncomplicated typhoid fever;
anticoagulant effect. step down therapy for
severe/complicated typhoid fever.
Avoid concomitant use with:
BCG (intravesical), sodium picosulfate, typhoid Contraindication: Known hypersensitivity to
vaccine- Cefalexin may reduce the cefixime and other cephalosporins, or
therapeutic effect of these drugs any component of the formulation.
Drugs causing renal impairment (e.g.,
aminoglycosides, furosemide and Dose:
gentamicin) – cephalosporins can cause Gonococcal conjunctivitis, CHILD, by mouth, 8
renal impairment; there may be an mg/kg/day together with 10- 12
increased risk of nephrotoxicity when mg/kg/day of azithromycin for 7-14
given concomitantly with these drugs. days.
Drugs delaying peristalsis (e.g., opiates and NOTE: In the treatment of ophthalmia
diphenoxylate with atropine) – these neonatorum, the following must be done
concomitantly:

Page | 167
ANTI-INFECTIVES
Irrigation of the eyes and eyelids,
antibiotic eye ointment, treatment for
chlamydia, and treatment likewise of
both the mother and her sexual partner
for gonococcal and chlamydial
infections.
Step down therapy for severe complicated
typhoid fever, by mouth, CHILD, 15-20
mg/kg every 12 hours for 7-10 days;
(maximum daily dose: 200 mg 1 tablet
every 12 hours); ADULT, 200 mg 1 tablet
every 12 hours for 7-10 days.
Uncomplicated gonococcal infections of the
cervix, urethras and rectum, as 2nd line
treatment when the 1st line injectable
Ceftriaxone is not available. CHILD, by
mouth, 8 mg/kg/day x 1 dose together
with 10-12 mg/kg/day of azithromycin.
ADULT, 400 mg x 1 dose together with
1g of azithromycin.
NOTE: Oral cephalosporins are not
recommended except when ceftriaxone
is not available. In this case, consider
cefixime but there should be a test of
cure after one week of treatment.
Uncomplicated typhoid fever (as second line
treatment), by mouth, CHILD, 15-20
mg/kg/day divided every 12 hours for 7-
10 days; maximum daily dose: 200 mg
every 12 hours; ADULT, 200 mg every 12
hours for 7-10 days.
NOTE: The use of second-line antibiotics
should be reserved for suspected or
proven Multi-Drug Resistant Typhoid
Fever (MDRTF) which is defined as
typhoid fever caused by Salmonella typhi
strains resistant to the first-line
recommended drugs for treatment,
namely, Ampicillin, Chloramphe-
nicol and Cotrimazole.
Dose Adjustments:
Elderly:
May be given the same dose recommended for
adults.
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted (maximum, 200
mg once daily); for severe impairment,
the patient should be referred to a
specialist.
Page | 168
CrCl 21-60 mL/ minute: Administer 75% of the
standard dose.
CrCl <20 mL/minute: Administer 50% of the
standard dose. 10% removed by
hemodialysis.
Precautions:
WARNING: Use with caution in patients
with a history of penicillin allergy, especially
IgE-mediated reactions.
Avoid use if with known history of immediate
hypersensitivity reactions to Beta
Lactam antibacterials (shock and
fatalities have been reported); renal
failure (avoid use); GI diseases; children
and infants <6 months (efficacy and
safety have not been established);
superinfection (prolonged use may
result in fungal or bacterial
superinfection, including C. difficile-
associated diarrhea (CDAD) and
pseudomembranous colitis. [NOTE:
CDAD has been observed >2 months
post-antibiotic treatment])
Pregnancy (not known to be harmful; use only
if clearly needed); breastfeeding
(monitor infant; probably present in milk,
but safe in usual dosage).
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea,
dyspepsia, flatulence, loose stools,
nausea, vomiting.
Less Common: Dizziness, headache.
Rare: Acute renal failure; agranulocytosis;
allergic reactions, including serum
sickness-like reactions, fever, arthralgia,
and anaphylaxis; angioedema;
antibiotic-associated colitis; aplastic
anemia; candidiasis; cholestatic
jaundice; confusion; dizziness, drug
fever, eosinophilia; erythema
multiforme; facial edema; fever;
hallucinations; headache; hemolytic
anemia; hepatitis; hyperactivity;
hyperbilirubinemia; hypertonia;
jaundice; leukopenia; nervousness;
neutropenia; pseudomembranous
colitis’ rash; reversible interstitial
nephritis; seizure; serum sickness-like
ANTI-INFECTIVES
reaction; sleep disturbances,
thrombocytopenia, Steven-Johnsons
syndrome (SJS); thrombocytopenia; toxic
epidermal necrolysis; urticaria; vaginitis;
vomiting.
Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – increased
prothrombin time, with or without clinical
bleeding; there may be an increased risk
of hemorrhage.
BCG and Typhoid vaccine 9affects only the live
attenuated Ty21a strain)- cefixime
reduces the therapeutic effects of these
vaccines.
Carbamazepine – its levels are elevated when
administered concomitantly with
cefixime.
Nephrotoxic drugs (e.g., ethacrynic acid,
furosemide, gentamicin and
vancomycin) – there may be an
increased risk of nephrotoxicity when
these drugs are administered with
cefixime (since cephalosporins may
possibly cause renal impairment).
Probenecid – this increases half-life and
prolongs the activity of cefixime (since
this competes with cephalosporins for
secretion via renal tubules).
Avoid concomitant use with:
Contraceptives, Oral – the contraceptive effect
of estrogens may be reduced by
cefixime.
Administration: May be taken with food or milk
to reduce GI discomfort. Shake oral
suspension well before use.
NOTE: Absorption delayed in the presence of
food.
Pregnancy Category: B
CEFTRIAXONE
Rx
Inj.: 250 mg vial + 2 mL 1% solution of
lidocaine (IM) (as disodium/sodium
salt)
500 mg vial + 2 mL 1% solution of
lidocaine (IM) (as disodium/sodium
salt)
1 g vial + 3.5 mL 1% solution of
lidocaine (IM) (as disodium/sodium
salt)
250 mg vial + 5 mL diluent (IV) (as
disodium/sodium salt)
Each duplex III container consists of: 1 g
ceftriaxone (as sodium) powder for
injection with 3.74% dextrose
solution for injection
A sterile, third-generation cephalosporin
antibiotic whose spectrum of activity is
wide, and has enhanced potency against
gram-negative organisms.
Indications: Treatment of gonococcal
conjunctivitis in adults and the neonates
(neonatal gonococcal conjunctivitis or
Ophthalmia Neonatorum);
uncomplicated gonococcal infections of
the cervix, urethra, rectum and the
pharynx; neonatal sepsis.
NOTE:
Refer patients with disseminated
gonococcal infection, or those with
bacteremia or arthritis, to the hospital
physician.
Contraindications: Known hypersensitivity to
cephalosporins or any component of the
formulation; porphyria; neonates less
than 41 weeks post-menstrual age;
neonates more than 41 weeks post-
menstrual age with jaundice,
hypoalbuminemia, acidosis or impaired
bilirubin binding; concomitant treatment
with IV calcium (including TPN) in
neonates over 41 weeks postmenstrual
age (due to risk of precipitation in urine
and lungs).
Page | 169
ANTI-INFECTIVES
Gastrointestinal: jaundice, poor feeding,
Do NOT use in hyperbilirubinemic or jaundiced abdominal distention.
neonates, particularly those who are Dermatologic: skin pustules,
premature since ceftriaxone is reported periumbilical erythema or purulence.
to displace bilirubin from albumin Musculoskeletal: edema or erythema
binding sites; avoid concomitant use overlying bones and joints.
with intravenous calcium-containing Others: Temperature >37.7⁰C (feels hot)
solutions/products in neonates (≤28 or <35.5⁰C (feels cold).
days) due to risk of precipitation of
ceftriaxone calcium salt. For Neonatal Sepsis:

Dose: For Ceftriaxone:

Gonococcal conjunctivitis, ADULT, 1g by IM Weight Age Dose
injection x 1 dose together with < 2 kg <7 days 50mg/kg q
azithromycin 1 g by mouth x 1 dose. 24 hours
Neonatal gonococcal conjunctivitis < 2 kg 8-28 50mg/kg q
(Ophthalmia neonatorum), by deep IM days 24 hours
injection or slow IV, NEONATE, 25-50 <1.2 kg >7 days 50mg/kg q
mg/kg as a single dose (maximum, 125 24 hours
mg). 1.2–2 >7 days 50mg/kg q
Uncomplicated gonococcal infections of the kg 24 hours
cervix, urethra, rectum and pharynx, >2 kg >7 days 50mg/kg q
CHILD, by IM injection or IV infusion, 24 hours
Ceftriaxone 25-50 mg/kg x 1 dose
(maximum: 125 mg IM); ADULT,
For Gentamicin:
Ceftriaxone 250 mg by IM injection x 1
dose together with Azithromycin 1 g by
Gestational Post-
Age natal Gentamicin
mouth x 1 dose.
Days
Neonatal sepsis (Sepsis neonatorum), by IM
injection or IV infusion, NEONATE, <29 weeks 0-7 • 5mg/kg
Ceftriaxone given as 1st line with q 48 hrs
gentamicin OR amikacin, with or without 8-28 • 4mg/kg
oxacillin OR vancomycin, using the q 36 hrs;
following doses to be >29 • 4mg/kg
given for 7-10 days or approximately 5-7 q 24 hrs
days after clinical signs and symptoms of
infection have disappeared. (Source: 30-34 0-7 •4.5mg/kg
National Antibiotics Guideline 2019): weeks q36 hrs
NOTE: >8 • 4 mg/kg
Neonatal sepsis: Neonates with q24 hrs
bacterial sepsis may present with non-
specific signs and symptoms or focal >35 weeks 0-7 • 4mg/kg
signs of infection. q24 hrs
Clinical criteria for diagnosis are: >8 • 4mg/kg
Neurologic: convulsions, drowsiness, or q24 hrs
unconsciousness, decreased activity, For Oxacillin:
bulging fontanel. Weight Age Dose
Respiratory: RR > 60 breaths/minute; <1.2 kgs <7days 25mg/kg q
grunting, severe chest indrawing, central 12 hours
cyanosis. 1.2-2 kgs <7days 25-
Cardiac: poor perfusion, rapid and weak 50mg/kg q
pulse. 12 hours

Page | 170
ANTI-INFECTIVES
>2 kgs <7days 25-50
mg/kg q 8
hours
<1.2 kg >7days 25 mg/kg q
12 hours
1-1.2 kg >7 days 25-50
mg/kg q 8
hours
>2 kg >7 days 25-50
mg/kg q 6
hours
Add oxacillin or vancomycin (MRSA) if
with skin/soft tissue infection.
(See under gentamicin, amikacin and
oxacillin for precautions and adverse
drug reactions and further information)
. precipitation in gallbladder; consider
RECONSTITUTION AND ADMINISTRATION OF
CEFTRIAXONE. According to
manufacturer’s directions. IM doses >1
g should be divided between more than
one site. Administer by IV infusion over
60 minutes in neonates.
NOTE: The duration of therapy for ceftriaxone
varies according to the course of the
disease. As with antibiotic therapy in
general, administration should be
continued for a minimum of 48-72 hours
after the patient has become afebrile, or
signs of bacterial eradication have been
obtained. Synergy between the drug and
aminoglycosides has been
demonstrated with many gram-negative
bacilli under experimental conditions.
Although enhanced activity of such
combinations is not always predictable,
it should be considered in severe, life-
threatening infections. Because of
physical incompatibility, the two drugs
should be administered separately at
the recommended dosages.
Dose Adjustments for Ceftriaxone:
Elderly:
Same dosage as in adult patients may be used
in the case of geriatric patients.
Renal and Hepatic Impairment:
For combined mild-to-moderate impairment,
dose reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions for Ceftriaxone:
Avoid if there is history of immediate
hypersensitivity Beta Lactams; severe
renal and hepatic impairment (monitor
plasma concentration); premature
neonates (may displace bilirubin from
serum albumin); Na restriction, heart
+
failure (injection contains 83 mg Na+/g);
chronic disease and malnutrition (risk of
bleeding due to low vitamin K stores);
treatment >14 days, renal failure,
dehydration, immobilized or
concomitant TPN (risk of ceftriaxone
discontinuation if symptomatic).
Pregnancy (not known to be harmful);
breastfeeding (excreted in low
concentration, but safe in usual dosage;
monitor infant).
Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-
associated diarrhea (CDAD) and
pseudomembranous colitis; CDAD has
been observed >2 months post-
antibiotic treatment.
Severe cases (including some fatalities) of
immune-related hemolytic anemia have
been reported in patients receiving
cephalosporins, including ceftriaxone;
Secondary to biliary obstruction, pancreatitis
has been reported rarely;
Use with caution in patients with a history of
penicillin allergy, especially IgE-
mediated reactions;
Adverse Drug Reactions of Ceftriaxone:
Common: Allergic skin reactions, including
dermatitis, exanthema and urticaria;
edematous swelling of skin and joints,
elevated serum liver enzymes,
induration, nausea, pain at the site of
injection, phlebitis, pruritus, rash,
symptomatic precipitation of ceftriaxone
calcium salt in the urine or gallbladder,
tightness, vomiting, warmth.
Page | 171
ANTI-INFECTIVES
Less Common: Abdominal discomfort, Avoid concomitant use with:
anorexia, confusion, diaphoresis, Bacteriostatic antibiotics (e.g., tetracyclines,
diarrhea, dizziness, emesis, chloramphenicol) – these may
eosinophilia, flushing, glossitis, antagonize the activity of ceftriaxone.
headache, increased serum creatinine,
leukopenia, mycosis of the genital tract, Administration of Ceftriaxone:
nausea, oliguria, pain, rash, stomatitis, Dosages >1 g of ceftriaxone should be
vertigo, tenderness at injection site, divided and injected on more than one
thrombocytosis. site. The reconstituted solution should
Rare: Agranulocytosis, allergic dermatitis, be shaken up to 1 minute to ensure
allergic pneumonitis, anaphylaxis, complete dissolution of ceftriaxone. For
anemia, antibiotic-associated colitis, IV, reconstitute to approximately 100
basophilia, biliary lithiasis, mg/mL, then dilute further to 10-40
bronchospasm, chills, cholestatic mg/mL. For IM, dilute with compatible
jaundice, coagulation disorders, colitis, fluid (NSS, D5W) to 250-350 mg/mL.
diaphoresis, dizziness dysgeusia, Reconstituted solutions should be inspected
dyspepsia, edema, erythema visually; only the clear solution which is
multiforme, fever, flatulence, flushing, free from visible particles should be
gall bladder sludge, gall stones, glossitis, used. They should be used immediately
granulocytopenia, hallucinations, after preparation.
hemolytic anemia, hepatitis, jaundice, Do not admix with aminoglycosides in same
leukopenia, Lyell’s syndrome, bottle/bag. Do not reconstitute, admix,
monocytosis, nephritis, oliguria, or co-administer with calcium-containing
palpitations, pancreatitis, prolongation solutions. Infuse intermittent infusion
of prothrombin time, renal and over 30 minutes.
pulmonary ceftriaxone-calcium NOTE: Reconstituted solutions retain their
precipitations, seizure, serum sickness- physical and chemical stability for 6
like reactions, Stevens-Johnsons hours at room temperature (or 24 hours
syndrome (SJS), stomatitis, at 5°C). They range from pale yellow to
thrombocytopenia, toxic epidermal amber in color, depending on the
necrolysis, vaginitis, vomiting. concentration and the length of storage.

Drug Interactions with Ceftriaxone: Pregnancy Category for Ceftriaxone: B

Monitor closely with:
Alcohol – this results in a disulfiram-like ATC Code:JO1DDO4
reaction (abdominal pain, flushing,
headache, nausea, vomiting and (See under Gentamicin, Amikacin and Oxacillin
tachycardia). for the dose adjustment, precautions,
Aminoglycosides – ceftriaxone may enhance adverse drug reactions, drug
their bactericidal activity against certain interactions and other information
pathogens; there may also be an regarding these drugs).
increased risk of ototoxicity and
nephrotoxicity.
BCG and Typhoid vaccine- Ceftriaxone reduces
the therapeutic effects of these
vaccines.
Contraceptives, Oral – their efficacy may be
reduced by ceftriaxone.
Vitamin K antagonists (e.g., warfarin)- its
therapeutic effect is enhanced by
ceftriaxone

Page | 172
ANTI-INFECTIVES
CEFUROXIME
Rx
Oral: 500 mg tablet (as axetil)
125 mg/5 mL granules for suspension,
70 mL (as axetil)
250 mg/5 mL granules for suspension,
120 mL
A second-generation cephalosporin with less
activity against gram-positive bacteria as
compared with the first-generation, but
has greater stability to hydrolysis by
beta-lactamases; active against beta-
lactamase-producing H. influenzae, S.
aureus, S. pneumoniae, Klebsiella spp.,
and penicillin-resistant pneumococci.
Indications: Susceptible upper and lower
respiratory tract infections: as
alternative treatment in low risk
community acquired pneumonia (CAP-
LR) in patients with stable co-morbid
illnesses or with recent antibiotic therapy
where Gram-negative bacilli can coexist;
Pediatric community acquired
pneumonia, non-severe (PCAP A/B);
acute exacerbations of chronic
bronchitis; alternative drug for acute
bacterial rhinosinusitis, acute otitis
media, acute sinusitis; asymptomatic
bacteriuria; alternative oral treatment of
Acute Uncomplicated Cystitis and Acute
Uncomplicated Pyelonephritis.
Contraindications: Known hypersensitivity to
cefuroxime and other cephalosporins, or
any component of the formulation.
Dose:
Acute bacterial exacerbation of chronic
bronchitis (ABECB), mild to moderate
infections, by mouth, ADULT, 500 mg 3x
daily for 5-10 days; for secondary
bacterial infections in chronic bronchitis,
ADULT, same dose for 5-10 days.
Acute bacterial rhinosinusitis, with severe
penicillin allergy, by mouth, CHILD, 30
mg/kg in divided doses every 12 hours
for 10 days; ADULT, 500 mg twice daily
for 5-7 days.
NOTE: Antibiotics for bacterial sinusitis
are given if: 1) with high fever and
purulent nasal discharge or facial pain
for >3 days; 2) still symptomatic after 10
days with no antibiotics; or, 3) symptoms
worsen after a typical viral illness that
lasted 5 days and had initially improved.
Acute otitis media, 2nd line treatment, no
anaphylaxis, by mouth, CHILD, 30 mg/kg
every 12 hours for 10 days (<2 years
old), 7 days (2-5 years old), 5-7 days (>5
years old); ADULT, 500 mg- 1 g in divided
doses every 12 hours for 7 days.
Acute otitis media, with clinical failure after 3
days, give by mouth, CHILD, 30 mg/kg in
divided doses every 12 hours for 10 days
(if <2 years old, OR with severe
symptoms regardless of age); or, give for
5-7 days (if > 2 years old with mild or
moderate disease).
NOTE: Clinical failure is defined as no
change in ear pain, fever, bulging
tympanic membrane, or otorrhea after 3
days of therapy.
Acute sinusitis, with clinical failure after 3
days, mild to moderate disease in adults,
ADULT, by mouth, 500 mg 2x a day for 7
– 10 days.
Acute uncomplicated cystitis, as alternative
treatment, by mouth, ADULT, 250 mg
twice daily for non-pregnant patients,
and 500 mg twice daily for pregnant
women, for 7 days. (See Clinical Practice
Guidelines in UTI for further information).
Acute uncomplicated pyelonephritis, as
alternative treatment, by mouth, ADULT,
500 mg twice daily for 14 days. (See
Clinical Practice Guidelines in UTI for
further information).
Asymptomatic bacteriuria, by mouth, ADULT, in
non-pregnant patient, 125-250 mg twice
daily for 7-14 days; in pregnant patient,
500 mg twice daily for 7 days. (See
Clinical Practice Guidelines in UTI for
further information).
Community-acquired pneumonia, Pediatric,
non-severe, PCAP A/B, by mouth, CHILD
>40 kg, 20-30 mg/kg in divided doses
every 12 hours for 7 days (See Interim
Practice Guidelines on PCAP).
Community-Acquired Pneumonia, Low-Risk
(CAP-LR) with stable co-morbid illness,
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ANTI-INFECTIVES
by mouth, ADULT, 500 mg twice a day for
5-7 days or 3-5 days if using with
azithromycin.
With co-existing Gram-negative bacilli,
by mouth, ADULT, 500 mg twice a day for
5-7 days. (See Interim Practice
Guidelines on CAP).
Dose Adjustments:
Elderly:
No dosage reduction is necessary in elderly
patients at recommended dosages.
Renal Impairment:
For marked impairment, dose should not
exceed 500 mg/day, by mouth, or 750
mg twice daily IM or IV. For severe
impairment, the patient should be
referred to a specialist.
CrCl 10-20mL/minute: Administer every 12
hours.
CrCl <10mL/minute: Administer every 24
hours.
Hemodialysis: Dialyzable (25%).
Peritoneal dialysis: Dose every 24 hours.
Continuous renal replacement therapy (CRRT):
1 g every 12 hours.
Precautions:
WARNING: Use with caution in patients
with a history of penicillin allergy.
History of hypersensitivity to cephalosporins
(serious and occasionally fatal;
discontinue if allergic reaction occurs);
may result in Candida overgrowth;
prolonged administration of cefuroxime
may result in overgrowth of non-
susceptible microorganisms; history of
colitis or diarrhea in association with
antibiotic treatment (increased risk of
antibiotic-associated colitis); renal or
hepatic impairment, or poor nutritional
state, patients receiving a protracted
course of antimicrobial therapy and
patients previously stabilized with
anticoagulant therapy (may be
associated with a fall in prothrombin
activity).
Pregnancy (given only if such use is considered
essential); breastfeeding (excreted in
Page | 174
human milk; use with caution when
administered to a nursing mother).
SKILLED TASKS. May impair ability to perform
skilled tasks, e.g., machinery or driving.
Adverse Drug Reactions:
Common: Diarrhea or loose stools, elevation in
AST, ALT and LDH; nausea, vomiting.
Less Common: Abdominal pain and cramps,
anorexia, chest pain, chills, dizziness,
dyspepsia, dysuria, flatulence,
headache, itch, mouth ulcers, pain and
inflammation at the injection site,
positive Coombs’ test, rash, shortness of
breath, sleepiness, somnolence,
superinfection, swollen tongue,
tachycardia, thirst, vaginitis, vulvar itch.
Rare: Agranulocytosis, allergic reactions,
including pruritus, serum sickness-like
reactions, rash, urticaria, fever,
arthralgia and anaphylaxis; antibiotic-
associated colitis, aplastic or hemolytic
anemia, bleeding, cholestatic jaundice,
confusion, encephalopathy, erythema
multiforme, hepatitis, leukopenia,
seizures, sleep disturbances,
thrombocytopenia, toxic epidermal
necrolysis.
Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – increased
prothrombin time, with or without clinical
bleeding; there may be an increased risk
of hemorrhage.
BCG and Typhoid vaccine (affect only the live
attenuated Ty21a strain)- Cefuroxime
may reduce the therapeutic effects of
these vaccines.
Nephrotoxic drugs (e.g., ethacrynic acid,
furosemide, gentamicin and
vancomycin) – there may be an
increased risk of nephrotoxicity when
these drugs are administered with
cefuroxime (since cephalosporins may
possibly cause renal impairment).
Probenecid – this increases half-life, and
prolong the activity of cefuroxime (since
this competes with cephalosporins for
secretion via renal tubules).
ANTI-INFECTIVES
Ranitidine – may result in lower bioavailability
of cefuroxime as compared with that of
the fasting state.
Avoid concomitant use with:
Contraceptives, Oral – the contraceptive effect
of estrogens may be reduced by
cefuroxime.
Administration: Swallow the tablet whole; it is
absorbed best if taken with a light meal.
Constituted suspensions or solutions
shall be used immediately.
For Oral suspension: Administer with food.
Shake well before use.
For IM: Inject deep IM into large muscle mass.
For IV: Inject direct IV over 3-5 minutes. Infuse
intermittent infusion over 15-30
minutes.
Pregnancy Category: B
SULFONAMIDES AND TRIMETHOPRIM
COTRIMOXAZOLE
Rx (Trimethoprim +
Sulfamethoxazole)
Oral: 400 mg sulfamethoxazole + 80 mg
trimethoprim tablet/capsule
800 mg sulfamethoxazole + 160 mg
trimethoprim tablet
200 mg sulfamethoxazole + 40 mg
trimethoprim/5 mL suspension, 70
mL and 120 mL
400 mg sulfamethoxazole + 80 mg
trimethoprim/5 mL suspension, 60
mL
A combination of a sulfonamide (5 parts) and
an inhibitor of dihydrofolate reductase (1
part), which provides synergistic
antimicrobial activity against many
gram-positive and gram-negative
organisms because of its sequential
inhibition of folate synthesis.
Indications: Uncomplicated typhoid or enteric
fever; choleraa (with severe diarrhea and
dehydration); acute diarrhea in children
due to Cyclospora; acute gastroentreritis
(acute bacterial diarrhea) in adults as
empiric therapy and specific therapy for
Shigella species; internal hordeolum or
stye (for MRSA, and community
associated); dacrocystitis, pertussis.
NOTE: Vibrio cholerae isolates remain
susceptible to first line agents:
chloramphenicol, co-trimoxazole and
tetracycline with 5% or less reported
resistance rates for 2019.
a Antimicrobial Resistance Surveillance
Program 2019 Annual Report, DOH-ARSP,
2020.
Antimicrobial Resistance ALERT!
• Use of cotrimoxazole is not
recommended for CAP due to continuing
increase in rate of resistance of S.
pneumoniae and H. influenzae.
• In UTI, among the Enterobacteriaceae,
resistance rates of E. coli to
cotrimoxazole have been increasing.
Contraindications: Known hypersensitivity to
sulfonamides, trimethoprim or any
component of the formulation; infants
<2 months of age; severe renal or
hepatic failure; megaloblastic anemia
(due to folic acid deficiency); blood
dyscrasias; acute porphyria; late
pregnancy (due to risk of neonatal
kernicterus, hemolytic anemia and
jaundice).
Dose:
NOTE: Doses are expressed as 800/160 mg = 800 mg
sulfamethoxazole with 160 mg trimethoprim
(equivalent to one double strength tablet);
40/8 mg is equivalent to 1 mL of oral liquid.
Acute diarrhea in children due to Cyclospora,
by mouth, CHILD, 10 mg TMP/50mg
SMX/ kg divided into 2 doses per day for
7-10 days.
Acute gastroenteritis (acute bacterial diarrhea
in adults), as empiric therapy, by mouth,
ADULT, 800/160 mg 2 x a day for 3 days.
Acute gastroenteritis (acute bacterial diarrhea
in adults) due to Shigella species, as
specific therapy, by mouth, ADULT,
800/160 mg 2 x a day for 3 days.
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ANTI-INFECTIVES
Cholera (acute bacterial diarrhea in adults due
to Vibrio cholera), by mouth, ADULT,
800/160 mg 2 x a day for 3 days.
Dacrocystitis, mild infection limited to lacrimal
sac, by mouth, ADULT, 800/160 mg tab,
2 tablets twice a day for 7-14 days.
Internal hordeolum (stye), MRSA, community-
associated, by mouth, ADULT, 800/160
mg, 2 tabs every 12 hours for 7-10 days.
Pertussis, by mouth, CHILD ≥ 2 months old,
40/8 mg/kg in 2 divided doses for 14
days; ADULT, 800/160 mg twice daily for
14 days.
Uncomplicated typhoid fever, by mouth,
ADULT, 800/160 mg every 12 hours for
14 days; CHILD, 8 mg/kg of
Trimethoprim in 2 divided doses every
12 hours for 14 days (Maximum
160/800 mg 1 tab every 12 hours).
Blood disorders (avoid unless under specialist
supervision; monitor blood count and
discontinue immediately if blood
disorder develops); rash (discontinue
treatment immediately); asthma; G6PD
deficiency (increased risk of hemolysis).
Pregnancy (first trimester: teratogenic effects
which include anencephaly, hypoplastic
left heart syndrome, choanal atresia,
transverse limb defect, diaphragmatic
hernia; third trimester: neonatal
hemolysis and methemoglobinemia);
breastfeeding (monitor infant for
jaundice: there is small risk of
kernicterus in jaundiced infants); G6PD-
deficient infants (risk for hemolysis due
to sulfamethoxazole); caution in ill or
premature infants; avoid in infants <6
weeks.

DILUTION AND ADMINISTRATION. According to Adverse Drug Reactions:

manufacturer’s directions. Common: Anorexia, diarrhea, fever,
hyperkalemia, hyponatremia, itch,
Dose Adjustments: nausea, rash, sore mouth,
Renal Impairment: thrombocytopenia, vomiting.
For mild-to-moderate renal impairment, dose Less Common: Drowsiness, headache,
reduction is warranted; contraindicated neutropenia, photosensitivity.
for severe impairment. Rare: Arthralgia, aseptic meningitis,
Clostridium difficile-associated disease,
Hepatic Impairment: convulsions, depression, erythema,
Contraindicated in significant hepatic hallucinations, hepatic necrosis,
impairment. hepatitis, hypoglycemia, jaundice,
Precautions: lowered mental acuity, megaloblastic
HIV infection (increased frequency of allergic anemia, myalgia, myocarditis,
reactions); photosensitivity; slow pancreatitis, peripheral neuropathy,
acetylator phenotype (increased risk of pulmonary infiltrates, Stevens-Johnson
adverse effects with sulfonamide); syndrome, SLE, toxic epidermal
treatment with oral typhoid vaccine necrolysis, urinary obstruction with
(cotrimoxazole is active against S. typhi, anuria or oliguria, uveitis, vasculitis,
and may inactivate the vaccine); vertigo.
systemic lupus erythematosus (may Drug Interactions:
worsen). Monitor closely with:
Elderly (increased risk of blood dyscrasias and Digoxin – possibly increased plasma digoxin
skin disorders). concentration.
Renal impairment (impairment increases risk Drugs causing potassium retention (e.g., ACE
of hyperkalemia or hypoglycemia; avoid inhibitors) – greater risk of
if severe and if plasma sulfamethoxazole hyperkalemia.
concentration cannot be monitored); low Other nephrotoxic drugs (e.g., gentamicin and
urine pH increases risk of crystalluria streptomycin) – cotrimoxazole can cause
(sulfamethoxazole is poorly soluble at nephrotoxicity; giving with other
low pH; maintain adequate fluid intake nephrotoxic drugs may cause additional
to prevent crystalluria). renal adverse effects.
Hepatic impairment (avoid if severe).
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ANTI-INFECTIVES
Phenytoin – antifolate effect and increased
plasma phenytoin concentration.
Rifampicin – this may decrease cotrimoxazole
concentration when used for prophylaxis
in HIV-positive patients, decreasing its
efficacy.
Administration: Should be taken WITH food;
this is best taken after meals with an
adequate amount of fluid.
Pregnancy Category: C
MACROLIDES
AZITHROMYCIN
Rx
Oral: 250 mg capsule (as base*/as dihydrate)
250 mg and 500 mg tablet (as
base*/as dihydrate/as
monohydrate)
200 mg/5 mL powder for suspension,
15 mL, and 60 mL (as base*/as
dihydrate/as monohydrate)
A macrolide antibiotic with slightly less activity
than erythromycin against gram-positive
bacteria, but enhanced activity against
some gram-negative organisms,
including H. influenzae and C.
trachomatis.
Indications: Suspected uncomplicated genital
chlamydial infections (e.g., urethritis,
cervicitis); ABECB; genital chlamydial
infections; conjunctivitis (chlamydial
trachomatis); low-risk community-
acquired pneumonia (CAP-LR) in adults,
without co-morbid illness when atypical
organisms (i.e., Legionella, Chlamydia,
or Mycoplasma) are suspected, or when
there is hypersensitivity to the beta-
lactams; non-severe CAP in child with
hypersensitivity to amoxicillin. (See
Interim Practice Guidelines in CAP and
pCAP); leptospirosis (as 2nd line
treatment); pertussis; pharyngitis or
tonsillitis with penicillin allergy;
uncomplicated typhoid fever (as 2nd line
treatment).
Contraindications: Known hypersensitivity to
azithromycin or any macrolide and
ketolide antibiotic, or any component of
the formulation; with history of
cholestatic jaundice or hepatic
impairment associated with prior
azithromycin use.
Dose:
Acute bacterial exacerbation of chronic
bronchitis (ABECB), severe, by mouth,
ADULT, 500 mg every 24 hours for 3
days.
Community-Acquired Pneumonia, Pediatric,
non-severe (pCAP A or B), for those with
hypersensitivity to amoxicillin, by mouth,
CHILD, 10 mg/kg single dose, maximum
of 500 mg/day, for 3 days or 10
mg/kg/day on day 1 then 5 mg/kg/day
on days 2 to 5 with maximum dose of
500 mg/day (See Interim Practice
Guidelines in pCAP).
Community-Acquired Pneumonia, Adult, by
mouth, ADULT,
• Low-risk, without co-morbid illness
when atypical organisms are suspected,
500 mg for 3-5 days;
• Low-risk, with stable co-morbid illness,
500 mg together with co-amoxiclav or
cefuroxime for 3-5 days;
• Moderate-risk, 500 mg daily together
with ampicillin- sulbactam or cefuroxime
for 7-10 days (or 3-5 days for azalides).
(See Interim Practice Guidelines in CAP).
Conjunctivitis, as Chlamydia trachomatis, by
mouth, NEONATE 3-10 days, 20 mg/kg
every 24 hours for 3 days.
Genital chlamydial infections (C. trachomatis),
as: • 1st line treatment: by mouth,
CHILD, >45 kg and <8 years old, 1 g x 1
dose; >8 years old, 1 g x 1 dose. ADULT,
1 g x 1 dose; Pregnant Women: 1 g x 1
dose.
• 2nd line treatment: by mouth, CHILD,
<45 kg, 20mg/kg daily x 3 days.
Gonococcal conjunctivitis, with presumptive
Chlamydia trachomatis co-infection, by
mouth, ADULT, 1 g per day together with
topical levofloxacin or tobramycin or
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ANTI-INFECTIVES
erythromycin ointment every 4 days for Severe impairment- reduce dose
2-3 weeks or until with resolution of
symptoms. Precautions:
NOTE: Ophthalmology referral is needed Cardiac conditions: prolongation of QT interval
to check for corneal perforation. (ventricular tachycardia reported);
Leptospirosis, as 2nd line treatment, by mouth, congenital long QT syndrome and family
Mild, CHILD, 1 g loading dose then 10 history of QT prolongation; torsades de
mg/kg for 2 days (maximum 500 pointes; ventricular arrhythmia and
mg/day); other arrhythmias; congestive heart
• Moderate to severe, by mouth, CHILD, failure; recent MI.
500 mg for 5 days. Proarrhythmic conditions (e.g., hypokalemia,
• Prophylaxis, by mouth, CHILD, 10 hypomagnesemia).
mg/kg x 1 dose (Maximum 500 mg); If Elderly patients (may be more susceptible to
children are exposed for more than 7 drug-associated QT prolongation).
days, the dose should be repeated after Renal impairment; exacerbations of
1 week. myasthenia gravis; diabetes (oral liquid
Pertussis, by mouth, INFANT <1 month, 10 contains sucrose 3.87 g/5 mL).
mg/kg every 24 hours for 5 days; INFANT Pregnancy; breastfeeding (limited drug
>2 months, 10 mg/kg on day 1 then 5 information available – use only if
mg/kg every 24 hours for 4 days; ADULT, adequate alternatives are not available).
500 mg on day 1 then 250 mg every 24
hours on day 2 to 5. Adverse Drug Reactions:
Pharyngitis or tonsillitis, with penicillin allergy, Common: Abdominal pain, arthralgia,
by mouth, CHILD, 12 mg/kg daily for 5 cramping, diarrhea, dizziness,
days; ADULT, 500 mg then 250 mg for 4 dyspepsia, flatulence, headache,
days or 500 mg per day for 3 days. malaise, nausea, pruritus, rash,
Uncomplicated gonococcal infection of the vaginitis, vomiting.
cervix, urethra, rectum and pharynx, Less Common: Abnormal heart rhythm, allergic
ADULT, as 1st line treatment, by mouth, reaction, anorexia, anxiety, chest pain,
1 g x 1 dose together with Ceftriaxone conjunctivitis, constipation, drowsiness,
250 mg by IM injection x 1 dose. edema, enteritis, fatigue, gastritis,
ADULT, as 2nd line treatment, by mouth, hyperkinesia, hypesthesia, hypotension,
1 g x 1 dose together with Cefixime by insomnia, leukopenia, liver disorders,
mouth 400 mg x 1 dose. CHILD, as 2nd myasthenia gravis, neutropenia,
line treatment, by mouth, 10-12 palpitations, pancreatitis, paresthesia,
mg/kg/day together with Cefixime by photosensitivity, rash, sleep
mouth 8mg/kg/day. disturbances, somnolence,
Uncomplicated typhoid fever, as 2nd line thrombocytopenia, tinnitus, urticaria,
treatment, by mouth, CHILD, 20 mg/kg vertigo.
daily for 5-7 days (Maximum 500 mg 1-2 Rare: Acute renal failure, agitation,
tablets every 24 hours); ADULT, 500 mg- angioedema, cholestatic jaundice,
1g for 5-7 days. convulsions, disturbances in taste and
vision, hemolytic anemia, hepatic
Dose Adjustments: necrosis and failure, interstitial
Renal Impairment: nephritis, seizures, syncope.
Mild impairment- same dose
Severe impairment- refer to specialist Drug Interactions:
NOTE: Macrolides inhibit P-glycoprotein, which
Hepatic Impairment (except for may lead to drug interactions (see
Contraindications stated above): Appendix).
Mild-to-moderate impairment- same Monitor closely with:
dose

Page | 178
ANTI-INFECTIVES
Antacids (e.g., aluminum or magnesium
hydroxide) – these may reduce the
absorption of azithromycin.
Contraceptives, Oral – their efficacy may be
reduced by azithromycin.
Avoid concomitant use with:
Amiodarone – increases QTc interval; may
cause possible serious or life-
threatening interaction.
Artemether + Lumefantrine – these may result
to potentially hazardous interactions
when given concomitantly with
azithromycin.
Digoxin – the serum levels of digoxin may be
increased by azithromycin, resulting in
enhanced actions and risk of toxicity.
Administration: Capsules should be taken at
least 1 hour before, or 2 hours after,
food intake; oral suspension can be
taken with food to reduce GI discomfort
and increase tolerability.
NOTE: Oral suspensions (100 mg/5 mL and
200 mg/5 mL) may be stored for 10 days
post-reconstitution and taken without
regard to food.
Pregnancy Category: B
infection (as combination therapy);
alternative in penicillin allergic patients.
Contraindications: Known hypersensitivity to
clarithromycin or any component of the
formulation; severe hepatic failure;
hypokalemia; patients with history of QT
prolongation or ventricular cardiac
arrhythmias; cholestatic jaundice or
hepatic dysfunction with prior
clarithromycin use.
Dose:
Acute bacterial rhinosinusitis (ABRS), with
severe penicillin allergy, by mouth,
CHILD, 15 mg/kg in divided doses every
12 hours x 10 days.
Acute bacterial exacerbation of chronic
bronchitis (ABECB), severe, by mouth,
ADULT, 500 mg twice daily for 5-10 days.
Acute otitis media, as 2nd line treatment, with
history of anaphylaxis to cephalosporins,
by mouth, CHILD, 15 mg/kg/day divided
every 12 hours for 10 days if <2 years
old, for 7 days if 2-5 years old, or, for 5-7
days if >5 years old.
Anti-Helicobacter pylori infection in peptic ulcer
disease, as combination therapy, by
mouth, ADULT, as follows:

Standard triple H. pylori eradication regimens.

CLARITHROMYCIN Regimen Adult Dose Duration
Rx If non-penicillin allergic:
Omeprazole Standard
dose For 10 to
Oral: 250 mg and 500 mg base tablet Clarithromycin 500 mg 2x 14 days
125 mg/5 mL and 250 mg/5 mL a day
granules/powder for suspension, 50 Amoxicillin 1 g 2x a
mL day
If penicillin allergic:
An erythromycin-derived, macrolide antibiotic,
Omeprazole Standard
which can be used in regimens for
dose For 10 to
Helicobacter pylori eradication, and for
Metronidazole 500 mg 3x 14 days
low-risk CAP when indicated.
a day
Clarithromycin 500 mg 2x
Indications: Low risk community-acquired
a day
pneumonia in adults (CAP-LR) due to
atypical organisms (i.e., Legionella,
Chlamydia, or Mycoplasma); non-severe Community-acquired pneumonia, in adults, by
CAP in children with hypersensitivity to mouth, ADULT,
amoxicillin; anti-Helicobacter pylori

Page | 179
ANTI-INFECTIVES
• Low-risk, without co-morbid illness
when atypical pathogens are suspected,
500 mg twice daily for 5-7 days;
• Low-risk, with stable co-morbid illness,
500 mg twice daily together with Co-
amoxiclav by mouth 1 g 2 x a day or
Cefuroxime by mouth 500 mg 2 x a day
for 5-7 days;
(See Interim Practice Guidelines in CAP).
Community-Acquired Pneumonia in children,
(pCAP A and pCAP B), for those with
hypersensitivity to amoxicillin, CHILD, 15
mg/kg/day, maximum of 1,000 mg/day,
in 2 divided doses for 7 days. See
Practice Guidelines – pCAP.
Community-acquired pneumonia in children,
by mouth, CHILD >5 years old and
adolescents, suspension 15 mg/kg in
divided doses every 12 hours for 10 days
Dental prophylaxis, with allergy to penicillins or
ampicillin, by mouth, CHILD, 15 mg/kg;
ADULT, 500 mg, given as single dose 30-
60 minutes before the procedure,
Eradication of H. pylori, by mouth, ADULT, 500
mg twice daily for 7 days in a
combination treatment.
Pertussis, by mouth, INFANT >2 month, 7.5
mg/kg every 12 hours for 7 days
(maximum 1 g per day); ADULT, 500 mg
twice daily for 7 days.
Pharyngitis or tonsillitis, with penicillin allergy,
by mouth, CHILD, 15 mg/kg in divided
doses every 12 hours for 10 days;
ADULT, 250 mg every 12 hours for 10
days.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: Increased risk of cardiac deaths.
In patients with a predisposition to QT interval
prolongation, including electrolyte
disturbances (e.g., uncorrected
hypokalemia or hypomagnesemia) and
Page | 180
concomitant use of drugs that prolong
QT interval (see Appendix – Table B).
Elderly patients may be more susceptible to
drug-associated QT prolongation.
History of ischemic heart disease, severe
cardiac insufficiency, ventricular
arrhythmia including torsades de
pointes, bradycardia (treatment risk-
benefit should be considered).
Hepatic dysfunction (discontinue immediately
if signs and symptoms of hepatitis
occur).
Antibiotic-associated colitis; myasthenia gravis
(may be aggravated).
Pregnancy (avoid use unless there is no
appropriate alternative therapy);
breastfeeding (safety has not been
established).
NOTE: Macrolides inhibit P-glycoprotein, which
may lead to drug interactions; CYP3A-
based interactions: clarithromycin (a
CYP3A inhibitor) may increase or prolong
both therapeutic and adverse effects of
drugs primarily metabolized by CYP3A
enzymes (see Appendix).
Adverse Drug Reactions:
Common: Taste disturbance.
Less Common: Abdominal discomfort,
diarrhea, hepatotoxicity (including
cholestatic jaundice), nausea, rash,
tinnitus, vomiting.
Rare: Antibiotic-associated colitis, arrhythmias,
pancreatitis, pulmonary infiltration with
QT interval prolongation, Stevens-
Johnson syndrome, torsades de pointes,
toxic epidermal necrolysis.
Drug Interactions:
Monitor closely with:
Anticoagulants (e.g., warfarin) – potential risk
of serious hemorrhage and significant
elevations in INR and prothrombin time.
Benzodiazepines (e.g., midazolam) – their
metabolism may be inhibited by
clarithromycin, and may prolong the
sedative and respiratory depressant
effects.
CYP3A4/5 inducers (see Appendix) – these
may induce metabolism of
clarithromycin; may result in
ANTI-INFECTIVES
subtherapeutic levels leading to reduced
efficacy.
Class IA or Class III antiarrhythmics or drugs
which prolong QT interval (see Appendix
– Table B) – QT interval may be
prolonged if given with the stated drugs,
increasing the risk of arrhythmia.
Hypoglycemic agents and insulin – can result
in significant hypoglycemia.
NNRTIs – these decrease concentration of
clarithromycin, and increase the
concentration of its active metabolite.
Phosphodiesterase inhibitors (e.g., sildenafil
and tadalafil) – their concentration may
be increased by clarithromycin.
Rifampicin – this may increase clarithromycin
metabolism, thus reducing its
antibacterial effect.
Theophylline – possibly increased serum
theophylline concentration.
Avoid concomitant use with:
Calcineurin inhibitors – their metabolism is
inhibited by clarithromycin, increasing
their concentration, and the risk of
nephrotoxicity and neurotoxicity.
Ergot alkaloids (e.g., ergotamine) – increased
risk of ergot toxicity.
HMG-CoA reductase inhibitors (e.g., lovastatin
and simvastatin) – their concentration is
possibly increased by clarithromycin,
thus increasing the risk of toxicity
(rhabdomyolysis).
Administration: The regular tablet and liquid
can be taken with or without food;
whereas, the long-acting tablet is usually
taken with food. The tablet should be
taken with a full glass of water; while the
long-acting tablet is swallowed whole (do
not split, chew or crush). Shake the
suspension well before use.
Pregnancy Category: C
ERYTHROMYCIN
Rx
Oral: 500 mg tablet (as stearate)
200 mg/5 mL granules/powder for
suspension, 60 mL (as ethyl
succinate)
A macrolide antibiotic that is effective in
treating infections caused by Chlamydia,
Mycoplasma, Pneumococcus and
Campylobacter spp.
Indications: Alternative to penicillin in
hypersensitive patients for treatment of
pharyngitis or tonsillitis and for
secondary recurrent rheumatic fever
prophylaxis; chlamydia; neonatal
chlamydial conjunctivitis; non-
gonococcal urethritis; Campylobacter
enteritis; and community-acquired
pneumonia in children >5 years old.
Contraindications: Known hypersensitivity to
erythromycin and other macrolides, or
any component of the formulation;
porphyria; severe hepatic impairment;
QT prolongation and ventricular cardiac
arrhythmias.
Dose:
Campylobacter enteritis, by mouth, CHILD, 40
mg/kg divided into 4 doses a day for 5
days.
Chlamydia (C. trachomatis), by mouth, CHILD,
< 45 kg, 50 mg/kg/day every 6 hours for
14 days; ADULT, as 2nd line treatment, as
erythromycin base, 500 mg 4 times daily
for 7 days; as erythromycin ethyl
succinate, 800 mg 4 x a day for 7 days.
For Conjunctivitis, Chlamydia
trachomatis, by mouth, NEONATE, 12.5
mg/kg every 6 hours for 14 days
Community-acquired pneumonia, in children
>5 years old, by mouth, CHILD >5 years,
50 mg/kg in divided doses every 6-8
hours for 10- 14 days.
Non-gonococcal urethritis, 2nd line treatment,
by mouth, ADULT, confirmed in
symptomatic men, as erythromycin
base, 500 mg 4x a day for 7 days.
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ANTI-INFECTIVES
Pharyngitis or tonsillitis, with penicillin allergy,
by mouth, CHILD, give as erythromycin
ethyl succinate, 40 mg/kg in divided
doses every 6 hours (maximum 1 g per
day) for 10 days; ADULT, give as
erythromycin ethyl succinate, 400 mg
every 6-12 hours for 10 days.
Pertussis prevention and treatment, by mouth,
ADULT, give as erythromycin estolate,
500 mg every 6 hours for 14 days;
CHILD, give as erythromycin estolate, 10
mg/kg/dose (maximum, 250 mg) every
6 hours for 14 days, or, as erythromycin
base, 40mg/kg/day in divided doses
every 6 hours for 7-14 days (maximum 1-
2 g/day).
Secondary prevention of recurrent rheumatic
fever attacks, if with penicillin allergy, by
mouth, ADULT, 20 mg/kg/day twice a
day (maximum 250 mg 2x a day). (See
under Phenoxymethylpenicillin or
Penicillin V for duration of prophylaxis).
Best to refer the patient to a specialist.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
Risk of sudden cardiac death from cardiac
causes when oral erythromycin used
concomitantly with drugs that inhibit
CYP3A4 (see Appendix).
Caution in ventricular cardiac arrhythmia and
QT prolongation.
Hepatic impairment (may cause idiosyncratic
hepatotoxicity) and renal impairment
(may cause ototoxicity); predisposition to
QT interval prolongation, including
electrolyte disturbances and
concomitant use of drugs that prolong
the QT interval (see Appendix – Table B).
Pregnancy (not known to be harmful);
breastfeeding (small amounts found in
milk – not known to be harmful; may
cause loose bowel actions in infant).
Page | 182
Adverse Drug Reactions:
Common: Abdominal pain, candida infections,
cramps, diarrhea, nausea, vomiting.
Less Common: Headache, rash, urticaria.
Rare: Blood dyscrasias, cardiac effects,
including prolonged QT interval;
cholestatic jaundice, C. difficile-
associated disease, hypersen- sitivity
reactions including anaphylaxis; infantile
hypertrophic pyloric stenosis,
myasthenia-like syndrome, pancreatitis,
psychiatric disturbances, ototoxicity,
toxic epidermal necrolysis.
Frequency not defined: Torsades de pointes,
ventricular arrhythmias, ventricular
tachycardia.
Drug Interactions:
NOTE: Macrolides inhibit P-glycoprotein, which
may lead to drug interactions (see
Appendix).
Monitor closely with:
Contraceptives, Oral – their efficacy may be
reduced by erythromycin.
Digoxin – its plasma concentration may be
increased by erythromycin, thus
increasing the risk of toxicity.
Avoid concomitant use with:
Artemether + Lumefantrine – these may result
to potentially hazardous interactions
when given concomitantly with
erythromycin.
CYP3A4 inhibitors (see Appendix) – these may
increase the concentration of
erythromycin and the risk of QT
prolongation.
HMG-CoA reductase inhibitors (e.g.,
atorvastatin, simvastatin) – their
concentration may be increased by
erythromycin, thus increasing the risk of
myopathy and rhabdomyolysis (stop
medication temporarily).
Hydrocortisone – its metabolism may be
inhibited by erythromycin.
Verapamil – this may increase erythromycin
concentration, thus increasing the risk of
serious prolongation of the QT interval.
Administration: Tablets and capsules should
be swallowed WHOLE; best taken on an
empty stomach 1 hour before, or 2
hours, after meals.
ANTI-INFECTIVES
Pregnancy Category: B
LINCOSAMIDES
CLINDAMYCIN
Rx
Oral: 150 and 300 mg capsule (as
hydrochloride)
75 mg/5 mL granules for suspension,
60 mL (as palmitate hydrochloride)
A semisynthetic derivative of lincomycin that is
effective for susceptible streptococci,
Staphylococcus aureus, and
Bacteroides spp. 90 percent of
clindamycin hydrochloride is absorbed
from the gastrointestinal tract.
Clindamycin palmitate must be
hydrolyzed in the GIT before it becomes
an active drug. It has no significant levels
in the cerebrospinal fluid.
Indications: Skin and soft tissue infections
caused by community-associated
methicillin-sensitive (MSSA) and
Methicillin-resistant Staphylococcus
aureus (MRSA); periodontal abscess;
pelvic inflammatory disease (together
with gentamicin).
General information on MRSA Infections: a
MRSA is a staphylococcal bacterium that has
developed resistance to several
antibiotics, including methicillin. In the
general community, it causes mostly
skin and soft tissue infections as well as
other infections. In a hospital, nursing
home, or other healthcare settings,
MRSA can cause severe infections such
as pneumonia, bloodstream and surgical
site infections.
How is MRSA spread in the community?
MRSA can affect anyone through transmission
via direct contact with an open wound or
sharing personal items, such as towels
and razors that have touched infected
skin. The risk for the infection is
increased in places or during situations
where there is crowding, skin-to-skin
contact, and shared equipment or
supplies (e.g., in schools, daycare
centers, and among patients with recent
in-patient hospital care.
How can MRSA be prevented?
Good personal hygiene is the most basic step
in preventing the disease.
For patients with MRSA, give the following
additional instructions: Cover the
wounds with clean, dry bandages; never
prick or pop the infected sores; always
wash the hands properly, especially after
contact with the infected site; do not
reuse or share personal items; wash
used sheets, towels, and clothes
properly; and strict compliance with
instructions regarding use of antibiotics
if these will become necessary.
What are the symptoms of MRSA?
Most staphylococcal skin infections, including
MRSA, appear as a sore or infected area
that may show: redness, swelling, pain
and warmth at the site, presence of pus
or other discharge; fever may or may not
be present.
What is the out-patient treatment of MRSA skin
and soft tissue infections?
The primary treatment of the focal skin and
soft tissue caused by community-
associated MRSA is incision and
drainage when mature (e.g., sore is
fluctuant).
The need for antibiotic treatment will depend
on several considerations that include:
rapid progression with cellulitis, severe
or more extensive disease or presence
at multiple sites, signs and symptoms of
systemic disease, abscess in an area
that is hard to drain (face, hand, or
genitalia), failure to respond to incision
and drainage, and presence of
comorbidities (immunosuppression, age
extremes, etc.). Local resistance to
antibiotics needs to be considered also.
Antibiotics that can be used in the local
outpatient setting may include:
clindamycin, cotrimoxazole or
doxycycline.
Page | 183
ANTI-INFECTIVES
Patients with a major abscess or wound
infection, infected ulcer, or a serious co-
morbid condition have to be
hospitalized.
a Centers for Disease Control and Prevention.
(2013). Methicillin-resistant
Staphylococcus aureus (MRSA)
infections. Retrieved from
http://cdc.gov/mrsa/.
Contraindications: Hypersensitivity to
clindamycin, lincomycin, or any
component of the formulation; history of
ulcerative or pseudomembranous colitis.
Dose:
Skin and soft tissue infections caused by
Methicillin-sensitive (MSSA) and
Methicillin-resistant Staphylococcus
aureus (MRSA) (Source: National
Antibiotic Guidelines 2019):
CHILD and INFANT, as 2nd line treatment,
by mouth, 10 - 30 mg/kg/day in 3-4
divided doses with maximum dose of 1.8
g/day for 7 – 10 days.
ADULT, Outpatient treatment of skin
abscess, boils and furuncles that are
large (>2 cm in diameter within an area
of erythema of >5 cm) or multiple
abscesses, or systemic inflammatory
skin response: treatment consists of
Incision and drainage PLUS Clindamycin,
by mouth, 300 – 450 mg (higher dose in
obese patients with BMI>40), 2x a day
for 5 – 10 days. (See the Clinical
Guidance on Common Bacterial Skin
Infections for more details on treatment
of MRSA).
Dentoalveolar abscess or peri-apical abscess,
as 2nd line treatment, by mouth, CHILD,
10mg/kg/day divided every 8 hours;
ADULT, 300 mg a day. Duration of
treatment is 7-14 days until local
inflammation has resolved completely.
NOTE: Dental consult is needed.
Periodontal abscess, as 2nd line treatment, by
mouth, CHILD, 10 mg/kg per day in
divided doses every 8 hours; ADULT, 150-
300 mg every 8 hours. Duration of
treatment is 7-14 days until local
inflammation has resolved completely.
Page | 184
NOTE: Dental consult is needed.
Pelvic inflammatory disease ADULT, 900 mg IV
every 8 hours given together with IV/IM
Gentamicin (See under Gentamicin for
treatment of PID).
Dose Adjustment:
Renal Impairment:
No dosage adjustment necessary.
Hepatic Impairment:
Use with caution in hepatic impairment,
monitor for hepatic abnormalities.
Precautions:
WARNING: Clostridium difficile-associated
diarrhea (CDAD) has been reported and
may range in severity from mild diarrhea
to fatal colitis. This may occur during
treatment or for >2 months after
discontinuation of treatment (more likely
to be refractory to antimicrobial therapy
and may require colectomy).
Reserve clindamycin for serious infection
where less toxic antibiotics are
inappropriate.
Avoid use for non-bacterial infection including
most upper respiratory tract infections.
Risk of potentially fatal pseudomembranous
colitis, fungal or bacterial superinfection
on prolonged use; discontinue therapy if
significant abdominal cramps, diarrhea
or passage of blood and mucus occur.
Severe skin reactions (e.g., toxic epidermal
necrolysis), some with fatal outcome,
have been reported; permanently
discontinue in these situations.
Parenteral product contains benzyl alcohol
which may cause “gasping syndrome”
and death in the newborn.
May increase the risk for antimicrobial-
resistant bacteria if used in the absence
of proven or strongly suspected
susceptible bacteria.
Lactation: possibly unsafe.
ANTI-INFECTIVES
Adverse Drug Reactions:
Common: Abdominal pain, diarrhea,
hypotension, jaundice, nausea, pruritus,
rash, urticaria, vomiting.
Frequency not defined: Agranulocytosis, C.
difficile-associated diarrhea,
eosinophilia (transient), esophagitis,
fungal overgrowth, granulocytopenia,
hypersensitivity neutron- penia,
polyarthritis, pseudomembranous
colitis, Stevens-Johnson syndrome,
thrombocytopenia, renal dysfunction.
Drug Interactions:
Monitor closely with:
Conjugated estrogens or estradiol or
ethinylestradiol – oral clindamycin
decreases level or effect of these drugs
by altering intestinal flora.
Digoxin – oral clindamycin increases level or
effect of digoxin through altering
intestinal flora.
Neuromuscular blockers (e.g., pancuronium) –
clindamycin increases effects by
pharmacodynamic synergism; possible
serious or life-threatening interaction;
risk of respiratory depression; use
alternatives if possible.
Warfarin – clindamycin increases effects of
warfarin (decreased vitamin-K producing
intestinal flora may increase INR after a
few days).
Avoid concomitant use with:
Typhoid vaccine, live – clindamycin decreases
effect of vaccine through
pharmacodynamic antagonism; high
likelihood of serious or life-threatening
interaction.
BCG vaccine, live – clindamycin decreases
effect of vaccine through
pharmacodynamic antagonism; high
likelihood of serious or life-threatening
interaction.
Erythromycin - antagonism may occur due to
competition at the binding sites.
Administration: May be taken with food. Do not
refrigerate reconstituted oral solution
since the solution will thicken;
reconstituted solution is stable for 2
weeks at room temperature.
Pregnancy Category: B
AMINOGLYCOSIDES
GENTAMICIN
Rx
Inj.: 10 mg/mL, 2 mL vial (IM, IV) (as sulfate)
40 mg/mL, 2 mL ampul/ vial (IM, IV) (as
sulfate)
An aminoglycoside that is not absorbed from
the gut, and should therefore be
administered by injection for systemic
infections caused by some gram-positive
and many gram-negative strains,
including Pseudomonas aeruginosa.
Indications: Used in combination with beta
lactams for the treatment of potential
sepsis in the neonate; sepsis
neonatorum; pelvic inflammatory
disease (with clindamycin).
NOTE:
Potential sepsis in the neonate:
Asymptomatic < 28 days old, with
documented maternal risk factors such
as history of UTI during the last trimester,
membranes ruptured > 18 hours before
delivery, fever > 38⁰C before delivery or
during labor and/ or presence of foul
smelling or purulent amniotic fluid.
Contraindications: Known hypersensitivity to
aminoglycosides or any component of
the formulation; perforated ear drum;
hepatic impairment; myasthenia gravis.
Dose:
NOTE: If the patient is >20% over ideal weight,
the ideal weight is generally used to
calculate the dose. However, some
practitioners prefer to use the adjusted
weight (adjusted weight = 0.4 𝑥𝑥 (actual
weight ⎼ ideal weight) + ideal weight).
Potential sepsis in neonates, by IV infusion,
with ampicillin (For dose of gentamicin
Page | 185
ANTI-INFECTIVES
used together with ampicillin for
treatment of potential sepsis in neonates,
see under Ampicillin).
Neonatal sepsis, by IV infusion, with
ceftriaxone (For dose of gentamicin used
with other antibiotics for the treatment of
neonatal sepsis, see under Ceftriaxone).
Pelvic inflammatory disease (with
clindamycin), by IV injection, ADULT,
loading dose of 2 mg/kg, then 1.5
mg/kg every 8 hours maintenance
dose; alternate therapy: 3 - 5 mg/kg
once daily.
(For dose of gentamicin used together
with clindamycin for Pelvic
Inflammatory Disease, see under
Clindamycin).
For inpatient regimen, continue
treatment until satisfactory response
for at least 24 hours occurs before
switching to outpatient regimen.
. with neuromuscular diseases e.g.,
NOTE: Treatment for <48 hours in people with
normal renal function does not require
gentamicin concentration monitoring.
DILUTION AND ADMINISTRATION. According to
manufacturer’s directions.
Dose Adjustments:
Neonates and Infants:
Adjust dosage; avoid prolonged use.
Obese patients:
To avoid excessive dosage, use ideal weight for
height to calculate dose and monitor
serum-gentamicin concentration closely.
Elderly:
For mild-to-moderate renal impairment, dose
reduction or dose interval extension is
warranted; for severe impairment, the
patient should be referred to a specialist.
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Page | 186
Precautions:
WARNING: Neurotoxicity, manifested as both
bilateral auditory and vestibular
ototoxicity, can occur in patients with
pre-existing renal damage and in
patients with normal renal function
treated at higher doses and/or for
periods longer than those
recommended.
Aminoglycosides are potentially nephrotoxic.
Risk is greater in patients with impaired
renal function and in those who receive
high doses or prolonged therapy.
Use with caution in premature infants and
neonates because of renal immaturity
and the resulting prolongation of serum
half-life of the drug.
Neuromuscular blockade and respiratory
paralysis have been reported following
parenteral injection of aminoglycosides.
Use with caution when giving in patients
myasthenia gravis.
Neuromuscular diseases (e.g., myasthenia
gravis) or conditions characterized by
muscle weakness (gentamicin may
impair neuromuscular transmission,
increasing risk of muscle weakness and
respiratory depression); renal
impairment; neonates (half-life
prolonged; decrease dose), infants, and
the elderly; obesity (use ideal body
weight to calculate dose and monitor
serum gentamicin concentration
closely).
Pregnancy (second and third trimesters:
auditory or vestibular nerve damage;
reserve for severe or life-threatening
infections for which safer drugs are
inappropriate; if administered, monitor
serum-gentamicin concentration);
breastfeeding (amount probably too
small to be harmful; monitor infant for
thrush and diarrhea).
Adverse Drug Reactions:
Common: Edema, gait instability, ototoxicity
(auditory and vestibular damage),
nephrotoxicity, reddening of the skin,
skin itching.
ANTI-INFECTIVES
Less Common: Rash. non-pregnant women); alternative
Rare: Anaphylaxis, antibiotic-associated colitis, treatment for Acute Uncomplicated
blood disorders, bronchospasm, CNS Cystitis.
effects, electrolyte disturbances,
nausea, neuromuscular blockade, Antimicrobial Resistance ALERT!
oliguria, peripheral neuropathy, • Antimicrobials such as ciprofloxacin
photosensitivity, stomatitis, vomiting. should not be administered to
patients with Salmonella
Drug Interactions: gastroenteritis since this is usually a
Monitor closely with: self-limited disease. a
Digoxin – the serum levels of digoxin may be
increased by gentamicin, resulting in • Due to emerging resistance of
enhanced actions and risk of toxicity. Shigellae to quinolones, judicious use
Ototoxic and nephrotoxic drugs (e.g., based on surveillance findings is
streptomycin) – possibly increased risk urged.a
of ototoxicity and nephrotoxicity.
• N. gonorrhoeae isolates have high
Avoid concomitant use with: rates of resistance against
Diuretics (e.g., furosemide) – these may ciprofloxacin at 80% (n=107); and
enhance aminoglycoside toxicity, tetracycline at 57% (n=69). This
increasing risk of ototoxicity. increased dramatically from 48% in
2008.a
Administration: Infuse gentamicin over 30-60
minutes; doses <120 mg may be given • Fluoroquinolones should not be used
as IV injection over 3-5 minutes. Final as first-line antibiotic for Acute
concentration of IV infusion should not Uncomplicated Cystitis due to its high
exceed 10 mg/mL. propensity for collateral damage.
Local studies have shown that
Pregnancy Category: D ciprofloxacin is now significantly less
effective therapy in tuberculosis.b

FLUOROQUINOLONES a
Carlos, C. Antimicrobial Resistance Surveillance Program
Annual Report 2018.
b
Carlos, C. Antimicrobial Resistance Surveillance Program
Annual Report, 2013.
CIPROFLOXACIN
Rx
Contraindications: Known hypersensitivity to
quinolones or any component of the
Oral: 250 mg and 500 mg tablet (as HCl) formulation; history of tendon disorders
related to quinolone use; not
A broad-spectrum, second-generation recommended in children and growing
carboxyquinolone that can be used adults (<18 years of age) due to
against gram-negative bacteria, possible risk of arthropathy; concurrent
including Neisseria, Salmonella, tizanidine use.
Shigella, Campylobacter and
Pseudomonas. Dose:
Acute bacterial gastroenteritis (Infectious
Indications: Acute gastroenteritis in adults; diarrhea) in adults, as:
suspected dysentery in infants and Empiric treatment, by mouth, ADULT,
children; chancroid; asymptomatic 500 mg every 12 hours for 3-5 days.
bacteriuria (in non-pregnant adults); Specific therapy for Shigella dysentery,
Acute Uncomplicated Pyelonephritis (in by mouth, 500 mg 2 x a day for 3 days.

Page | 187
ANTI-INFECTIVES
Antimicrobial Resistance ALERT! In
Salmonella gastroenteritis, increasing
rates of Ciprofloxacin resistance should
remind clinicians to use antibiotics
judiciously, as this is a self-limiting
disease.
Acute uncomplicated pyelonephritis, by mouth,
ADULT, 500 mg twice daily for 7-10 days.
Acute uncomplicated cystitis, only as
alternative treatment, by mouth, ADULT,
250 mg twice daily for 3 days. See
Clinical Practice Guidelines – UTI for
further information.
Asymptomatic bacteriuria, by mouth, ADULT, in
non-pregnant patients, 250 mg twice
daily for 7-14 days.
Chancroid, by mouth, ADULT, 500 mg twice
daily for 3 days.
Suspected dysentery in infants and children, by
mouth, INFANT and CHILD, as follows:
0-2 months old: 30 mg/kg/day in 2
divided doses for 3 days;
2 months – 5 years old: 30 mg/kg/day
in 2 divided doses for 3 days.
(Refer to the Interim Guidelines on
Infectious Diarrhea and the National
Antibiotics Guidelines)
Typhoid fever, severe/complicated, as:
Step-down treatment following
intravenous antibiotics, by mouth,
CHILD, 30 mg/kg in divided doses every
12 hours for 7-10 days (maximum 500
mg, 1 tab every 12 hours); ADULT, 500
mg/tab, 1 tab every 12 hours for 7-10
days.
Typhoid fever, uncomplicated, by mouth,
CHILD, as 2nd line treatment, 30 mg/kg in
divided doses every 12 hours for 7-10
days; ADULT, as 1st line treatment, 500
mg, 1 tablet every 12 hours for 7-10 days.
Dose Adjustments:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Hepatic Impairment:
Same dosage as in patients with normal
hepatic function may be used in patients
with mild-to-moderate hepatic
Page | 188
impairment; for severe impairment, refer
to a specialist.
Precautions:
WARNING: Associated with an increased risk of
tendinitis and tendon rupture; this risk is
further increased in older patients,
usually those older than 60 years; in
kidney, heart, and lung transplant
recipients; and with the concomitant use
of steroid therapy.
May exacerbate muscle weakness in patients
with myasthenia gravis; avoid
quinolones with known history of
myasthenia gravis.
History of epilepsy or conditions that
predispose to seizures; myasthenia
gravis; G6PD deficiency (increased risk
of hemolytic anemia); risk of crystalluria
(avoid excessive alkalinity of urine and
ensure adequate fluid intake); renal
impairment; avoid exposure to excessive
sunlight (discontinue if photosensitivity
occurs); children or adolescents (see
below); rarely tendon damage (see
below).
Pregnancy (avoid use; arthropathy reported in
animal studies; safer alternatives are
available), and breastfeeding (amount
too small to be harmful; use alternative
drugs if possible).
USE IN CHILDREN: Ciprofloxacin causes
arthropathy in weight-bearing joints of
immature animals, and is therefore
generally not recommended for use in
children and growing adolescents.
However, the significance of this effect in
humans is uncertain and in some
specific circumstances, short-term use
of ciprofloxacin in children may be
justified.
TENDON DAMAGE: Tendon damage, including
rupture, has been reported rarely in
patients receiving quinolones. Tendon
rupture can possibly occur within 48
hours of starting treatment. Healthcare
workers should always be aware that:
• Quinolones are contraindicated in
patients with a history of tendon
disorders related to quinolone use.
ANTI-INFECTIVES
• Elderly patients are more prone to Phenytoin – its concentration and therapeutic
tendinitis. effect may be decreased by
• The risk of tendon rupture is ciprofloxacin.
increased by the concomitant use of Theophylline – its metabolism may be inhibited
corticosteroids. by ciprofloxacin, thereby increasing its
• If tendinitis is suspected, the concentration and toxicity (more likely in
quinolone should be discontinued the elderly).
immediately. Warfarin – its effect may be enhanced by
SKILLED TASKS. May impair ability to perform ciprofloxacin, thereby increasing risk of
skilled tasks, e.g., operating machinery bleeding (monitor INR).
or driving.
Avoid concomitant use with:
Adverse Drug Reactions: Antacids (e.g., aluminum or magnesium
Common: Abdominal pain, diarrhea, hydroxide) – these bind to ciprofloxacin
dyspepsia, flatulence, itch, nausea, rash, in the GI tract, thereby reducing its
vomiting. absorption and activity (give it at least 2
Less Common: Abnormal liver function tests, hours, before, or 4-6 hours after, the
agitation, anorexia, arthralgia, arthritis, antacid).
confusion, decreased appetite and food Artemether + Lumefantrine – these may result
intake, depression, dizziness, to potentially hazardous interactions
drowsiness, hallucinations, fever, when given concomitantly with
headache, myalgia, superinfections, ciprofloxacin.
restlessness, sleep and taste disorders, Calcium – this binds to ciprofloxacin in the GI
urticaria. tract; reducing its absorption and activity
Rare: Agranulocytosis, anaphylaxis, bone (separate doses by at least 2 hours).
marrow depression, C. difficile- Iron – this binds to ciprofloxacin in the GI tract;
associated disease, dyspnea, edema, reducing its absorption and activity (take
erythema multiforme, erythema ciprofloxacin at least 2 hours before
nodosum, fixed drug eruptions, hearing iron).
loss, hematuria, hemolytic anemia, Seizure-inducing drugs (see Table C for other
hepatitis, hyperglycemia, hypoglycemia, drugs which may cause seizures) – there
hypotension, interstitial nephritis, may be an increased risk of seizures
jaundice, leukopenia, neutropenia, when these are given concomitantly with
pancreatitis, pancytopenia, petechiae, ciprofloxacin (ciprofloxacin may cause
photosensitivity reactions, psychotic seizures).
reactions, renal impairment, seizures, Sucralfate – this chelates ciprofloxacin,
serum sickness-like reactions, Stevens- thereby reducing its absorption and
Johnson syndrome, syncope, activity.
tachycardia, tendonitis, Thyroid hormones – their absorption may be
thrombocytopenia, toxic epidermal interfered by ciprofloxacin, thereby
necrolysis, vasculitis. resulting in hypothyroidism (acquire
thyroid function tests if needed).
Drug Interactions: Zinc salts – these bind to ciprofloxacin in the
NOTE: Ciprofloxacin inhibits CYP1A2, and may GI tract, thereby reducing its absorption
affect drugs metabolized by this enzyme and activity (take ciprofloxacin at least 2
(see Appendix). hours before zinc).

Monitor closely with: Administration: May be taken with or without

Ibuprofen – this may increase the risk of food; do not take with antacids, iron or
convulsions. dairy products.

Pregnancy Category: C

Page | 189
ANTI-INFECTIVES
IMIDAZOLE DERIVATIVES
METRONIDAZOLE
Rx
Oral: 250 mg and 500 mg base tablet
125 mg base/5 mL (200 mg/5 mL as
benzoate) suspension, 60 mL
A nitroimidazole, antiprotozoal drug, which has
potent antibacterial activity against
anaerobes, including Bacteroides and
Clostridium spp.
Indications: Acute ulcerative gingivitis; juvenile
periodontitis; bacterial vaginosis; for H.
pylori eradication (as combination
therapy - see under Eradication of H.
pylori infection in peptic ulcer disease);
for amoebiasis, giardiasis, urethritis and
vaginitis due to Trichomonas (See under
Antiprotozoals in the section on Anti-
Parasitic Products).
Contraindications: Known hypersensitivity to
metronidazole or any component of the
formulation; chronic alcohol
dependence.
Dose:
Acute gingivitis, oral anaerobes, by mouth,
CHILD > 12 years old, 30 mg/kg in
divided doses every 6 hours with
penicillin for 7-10 days; ADULT, 500 mg
every 8 hours with penicillin V potassium
for 7-10 days.
Acute necrotizing ulcerative gingivitis, oral
anaerobes, by mouth, ADULT, 500 mg
every 8 hours together with Penicillin VK
500 mg by mouth every 6 hours for 10
days.
NOTE: Refer to a dentist for gingival
curettage.
Amebiasis (Entamoeba histolytica), by mouth,
(See under Antiprotozoals in the section
on Anti-Parasitic Products).
Bacterial vaginosis, by mouth, CHILD, 15
mg/kg divided doses every 12 hours
daily x 7 days; ADULT, 500 mg twice daily
for 7 days.
Page | 190
Giardiasis, by mouth, (See under
Antiprotozoals in the section on Anti-
Parasitic Products).
Juvenile periodontitis, by mouth, CHILD, <8
years old, 50 mg/kg divided every 8
hours per day for 7 days.
NOTE: Refer to a dentist for root
debridement and plaque control which
may control the infection. If there is no
response to these, antibiotics should be
started.
Urethritis and vaginitis due to Trichomonas
(See under Antiprotozoals in the section
on Anti-Parasitic Products).
Dose Adjustments:
Renal Impairment:
Dose adjustment is not usually necessary.
However, consider reducing dose during
long-term therapy. For severe
impairment, the patient should be
referred to a specialist (as metabolites
may accumulate, possibly causing
adverse effects).
Hepatic impairment:
For severe liver disease, reduce total daily
dose to one-third or one-half, and give
once daily (risk of drug accumulation
and toxicity in severe impairment,
especially if renal impairment is also
present).
Precautions:
Treatment with disulfiram may cause psychotic
reactions; treatment with fluorouracil
(avoid combination); disulfiram-like
reaction with alcohol.
Hepatic impairment and hepatic
encephalopathy.
Renal impairment; congestive heart failure;
history of blood dyscrasias; history of
CNS disorders, and seizures
(nitroimidazoles are neurotoxic and may
aggravate existing neurological
disease); clinical and laboratory
monitoring recommended in courses
lasting longer than 10 days.
Pregnancy (avoid use in early pregnancy; if this
is to be administered, avoid high-dose
regimens; take in divided doses if
possible); breastfeeding (significant
ANTI-INFECTIVES
amounts in milk; may cause bitterness in
milk; use in divided doses if given after
breastfeeding rather than single daily
doses; avoid large doses; use an
alternative drug if possible).
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, CNS
effects (e.g., dizziness), constipation or
diarrhea, GI disturbances, headache,
metallic taste, nausea, vomiting.
Less Common: Drowsiness, furry tongue (due
to growth of Candida), glossitis,
paresthesia, stomatitis.
Rare: Agranulocytosis, anaphylactic shock,
angioedema, aplastic anemia,
cholestatic hepatitis, C. difficile-
associated disease, darkening of urine,
seizures, hypersensitivity reactions,
jaundice, leukopenia (on prolonged or
high dosage regimens), myalgia, myopia,
optic neuritis, pancreatitis, peripheral
neuropathy, psychotic disorder, raised
liver enzyme, Stevens-Johnson
syndrome, thrombocytopenia, urethral
discomfort.
Drug Interactions:
Monitor closely with:
Contraceptives, Oral – their efficacy may be
reduced by metronidazole.
Phenobarbital – this may increase metabolism
of metronidazole, and reduce its
concentration with possible treatment
failure (monitor clinical effect as there
may be a need to increase its dose,
possibly by 2-3 times).
Avoid concomitant use with:
Alcohol – this results in a disulfiram-like
reaction (abdominal pain, flushing,
headache, nausea, vomiting,
tachycardia); (avoid alcoholic drinks
during, and for at least 24 hours after
treatment).
Administration: Tablets should be swallowed
whole with water, during or after a meal;
oral suspension should be taken one
hour before a meal or on an empty
stomach.
Pregnancy Category: B
ATC Code: P01AB01
NITROFURAN DERIVATIVES
URINARY ANTISEPTIC
NITROFURANTON
Rx
Oral: 50 mg and 100 mg capsule (as
Macrocrystals)
Nitrofurantoin is bacteriostatic and
bactericidal for many gram-negative and
gram-positive organisms, but may not
affect P. aeruginosa and many strains of
proteus; the macrocrystalline form is
absorbed and excreted slowly, and is
better tolerated with lower incidence of
GI side effects.
Indications: Treatment of acute,
uncomplicated cystitis in non-pregnant
women; asymptomatic bacteriuria;
recurrent urinary tract infection in non-
pregnant women (for asymptomatic
bacteriuria in pregnancy, urine culture is
necessary).
Contraindications: Known hypersensitivity to
nitrofurantoin or any component of the
formulation; anuria, oliguria, or
significant impairment of renal function;
previous history of cholestatic jaundice
or hepatic dysfunction associated with
prior nitrofurantoin use; for infants <1
month of age (increased risk of
hemolytic anemia); G6PD-deficiency,
including breastfeeding of affected
infants (only small amounts in milk but
may be enough to produce hemolysis in
G6PD-deficient infants); pregnancy at
term (third trimester: may produce
neonatal hemolysis if used at term);
porphyria.
Dose:
Page | 191
ANTI-INFECTIVES
Asymptomatic bacteriuria, by mouth, ADULT, in
non-pregnant patients, 100 mg 4 times
daily for 7-14 days; in pregnant women,
100 mg 4 times daily for 7 days.
Acute uncomplicated cystitis in non-pregnant
women, by mouth, ADULT, 100 mg 4
times daily for 5 days; in pregnant
women, 100 mg 4 times daily for 7 days;
CHILD >1 year, 5-7 mg/kg/day divided
in 4 doses (maximum dose, 400
mg/day). (See Clinical Practice
Guidelines in Urinary Tract Infection for
further information).
Recurrent urinary tract infection in non-
pregnant women, by mouth, ADULT
(women), 100 mg at bedtime for 6-12
months either continuously or as post-
coital prophylaxis.
Dose Adjustments:
Renal Impairment:
Avoid use (peripheral neuropathy; ineffective
because of inadequate urine
concentrations).
Hepatic Impairment:
Avoid use (cholestatic jaundice and chronic
active hepatitis have been reported).
Precautions:
This is not indicated for the treatment of
pyelonephritis; it is ineffective in alkaline
urine.
Pulmonary toxicity and disorders (monitor lung
and liver function on long-term therapy;
discontinue use if the lung function
deteriorates; acute, subacute or chronic
pulmonary reactions have been
observed); susceptibility to peripheral
neuropathy (rare; risk may be increased
in patients with anemia, renal
impairment, diabetes, vitamin B
deficiency, debilitating disease, or
electrolyte disturbance); risk of optic
neuritis; hepatic reactions (rare, but
severe and sometimes fatal reactions
have been associated with its use;
monitor liver function tests periodically);
hemolytic anemia; neurological or
allergic disorders; folate deficiency;
prolonged use may result in fungal or
bacterial superinfection; urine may be
colored yellow or brown.
Page | 192
The elderly (avoid use for long-term
suppression due to potential for
pulmonary toxicity; use in the elderly,
particularly females receiving long-term
prophylaxis for recurrent UTIs, has also
been associated with an increased risk
of hepatic toxicity and peripheral
neuropathy; monitor closely for toxicities
during use).
Pregnancy (when given during the 2nd trimester
until 32 weeks age of gestation) may
cause birth defects and complications
(see under Guidelines on UTI).
NOTE: During long-term treatment, monitor:
• Pulmonary function
• Liver function every month for 3
months, then every 3 months, since
onset of hepatotoxicity may be
insidious
• Renal function since peripheral
neuropathy is more likely to occur if
this is impaired
• For the development of paresthesia
as stopping treatment early can
prevent severe neuropathy
Adverse Drug Reactions:
Common: Abdominal pain, allergic skin
reactions, anorexia, diarrhea, headache,
nausea, vomiting.
Less Common: Dizziness, drowsiness, vertigo.
Rare: Alopecia, anaphylaxis, arthralgia, benign
intracranial hypertension; blood
disorders, drug fever, cholestatic
jaundice, erythema multiforme,
exfoliative dermatitis, hepatotoxicity,
lupus-like syndrome, pancreatitis,
peripheral neuropathy, pulmonary
reactions, Stevens-Johnson syndrome.
Drug Interactions:
NOTE: The bioavailability of nitrofurantoin is
usually increased by medicines that
reduce gastric emptying time, such as
diphenoxylate and atropine.
Monitor closely with:
Aldosterone-blocking agents (eplerenone and
spironolactone) – their hyperkalemic
effect may be enhanced by
nitrofurantoin.
ANTI-INFECTIVES
Sedatives (e.g., alcohol) – their effect may be
potentiated when taken with
nitrofurantoin.
Avoid concomitant use with:
Antacids – these reduce absorption of
nitrofurantoin, thus decreasing its
clinical effect.
Administration: Take with meals or milk to
improve absorption and decrease
adverse effects (e.g., nausea).
Pregnancy Category: B
ANTI-FUNGALS
CLOTRIMAZOLE
Rx
Cream: 1% (10mg/ g), 3 g, 10 g and 20 g
aluminum collapsible tube
2% (20 mg/g), 30 g aluminum
collapsible tube
Vaginal: 1%, 10 g aluminum collapsible tube
Ear solution: 1% otic solution
A broad-spectrum imidazole active against
fungi, (both dermatophytes and yeasts),
and gram-positive cocci (Staphylococcus
and Streptococcus spp.).
Indications: Anogenital and vulvovaginal
candidiasis; ringworm; skin infections,
including pityriasis versicolor and
dermatophytosis (e.g., tinea corporis,
tinea pedis, tinea cruris); protozoal
infections (e.g., trichomoniasis);
otomycosis.
Contraindications: Known hypersensitivity to
clotrimazole or any component of the
formulation; severe liver impairment.
Dose:
Anogenital candidiasis, by topical use, ADULT,
apply 1% cream to anogenital area 2-3
times daily.
Fungal otitis externa (otomycosis), by topical
use, CHILD, instill 2-3 drops every 8 – 12
hours for 10-14 days; ADULT, instill 2-3
drops every 8 – 12 hours for 10-14 days;
Cutaneous candidiasis (Candida albicans and
other species), by topical use, apply 1%
cream 2-3 times daily for 1-2 weeks.
NOTE: Common types of candida skin
infections include: intertrigo, diaper
dermatitis, erosion interdigitalis,
blastomycetica, perianal dermatitis,
balanitis, and paronychia.
Pityriasis versicolor, by topical use, apply 1%
cream 2-3 times daily for 1-2 weeks
Tinea corporis/ cruris, by topical use, apply 1%
cream 2 x a day for 2-4 weeks.
Tinea pedis, by topical use, 1% cream, apply 2
x a day for 2-4 weeks.
Vulvovaginal candidiasis, intravaginal
administration (10% vaginal cream),
ADULT, 5 g of a single dose at night,
repeated once if necessary (1% is to 6
doses; 2% is to 3 doses).
Vulvovaginal candidiasis, vaginal
administration (pessary), ADULT, insert
100 mg at night for 6 nights or 200 mg
at night for 3 nights, or 500 mg at night
as a single dose.
Dose Adjustment:
Vulvovaginal candidiasis in Pregnancy:
Requires a longer duration of treatment, about
7 days, to clear the infection (oral
antifungal treatment should be avoided).
Precautions:
Should be discontinued if irritation or
sensitivity occurs; should not come in
contact with the eyes; this damages
latex condoms and diaphragms (advise
contraceptive precautions).
Pregnancy (safety in the first trimester has not
yet been established).
Adverse Drug Reactions:
Common: Local pain or discomfort.
Less Common: Blistering, burning, edema,
erythema, general skin irritation, itch,
peeling, pruritus, stinging.
Rare: Allergic reactions
Drug Interaction:
Page | 193
ANTI-INFECTIVES
Monitor closely with:
Simvastatin – increased risk of myopathy.
Administration: For the topical solution, gently
massage sufficient amount into the
affected and surrounding skin areas
twice a day, in the morning and evening.
If the feet are infected, they should be
washed and dried, especially between
the toes, before applying the cream.
Pregnancy Category: B
ANTI-MYCOBACTERIALS
ANTITUBERCULOSIS
For details on the recommended dosing,
please refer to the National Tuberculosis
Control Program Manual of Procedures.
SINGLE DOSE FORMULATIONS
ETHAMBUTOL
Rx
Oral: 200 mg and 400 mg tablet (as HCl)
A water-soluble, heat-stable, bacteriostatic
agent used in combination with other
drugs as first-line agents for the
treatment of tuberculosis.
Indication: Tuberculosis (especially in cases of
allergy to a fixed-dose combination
where a drug is introduced separately, or
in the presence of renal or hepatic
impairment).
Contraindications: Known hypersensitivity to
ethambutol or any component of the
formulation; optic neuritis; children <6
years (unable to report symptomatic
visual disturbances).
Dose:
Page | 194
NOTE: Doses may need adjustment if
significant weight gain occurs during
treatment. Use doses below for the first
2 months of the 6-month multidrug
regimen).
Tuberculosis, by mouth, ADULT, 15 mg/kg
(range: 15-20 mg/kg) daily, not to
exceed 1.2 g daily; CHILD, 20 mg/kg
(range: 15-25 mg/kg) daily, not to
exceed 1.2 g daily. (Refer to the DOH
National Tuberculosis Control Program).
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance
<30 mL/minute or for adult patients
receiving hemodialysis: 15-25 mg/kg
per dose three times per week (not
daily ). Refer to the Tables in the section
on Recommended Treatment Regimen
for Tuberculosis.
Precautions:
Ocular examination is recommended before,
and during, treatment; warn patients to
report visual changes; elderly; young
children; further deterioration in vision
may occur where there are visual defects
(e.g., diabetic retinopathy, cataract);
renal impairment (monitor plasma
ethambutol concentration); gout (acute
attack may occur).
Pregnancy (not known to be harmful);
breastfeeding (amount too small to be
harmful).
NOTE: Patients should report visual
disturbances immediately and
discontinue treatment; children who are
incapable of reporting symptomatic
visual changes accurately should be
given alternative therapy, as should, if
possible, any patient who cannot
understand warnings about visual
adverse effects.
Adverse Drug Reactions:
Common: Retrobulbar neuritis (resulting in
loss of visual acuity and red-green color
blindness).
Less Common: Abdominal pain, anorexia,
confusion, disorientation, hallucinations,
headache, malaise, nausea, vomiting.
ANTI-INFECTIVES
Rare: Acute gout, hypersensitivity reaction
including anaphylaxis, hyperuricemia,
neutropenia, peripheral neuritis, renal
failure, thrombocytopenia.
Drug Interaction:
Monitor closely with:
Thiazide diuretics – serum uric acid levels may
be elevated.
Avoid concomitant use with:
Aluminum salts – may delay and reduce the
absorption of ethambutol.
Administration: Tablets should be taken with
food.
Pregnancy Category: C
ISONIAZID
Rx
Oral: 300 mg and 400 mg tablet
200 mg/5 mL syrup, 120 mL
A hydrazide of isonicotinic acid, which is a
bactericidal agent used in combination
with other drugs as first-line agents for
treating tuberculosis.
Indications: Tuberculosis (especially in cases
of allergy to a fixed-dose combination
where a drug is introduced separately, or
in the presence of renal or hepatic
impairment).
NOTE: Preventive therapy for specific
situations: close family contacts of
open/active tuberculosis cases
especially in those <5 years; for latent
TB infection; for the prevention of
recurrence of infection in patients at risk
of reactivation.
Contraindications: Known hypersensitivity to
isoniazid or any component of the
formulation; drug-induced hepatic
disease.
Dose:
Tuberculosis, treatment, by mouth, ADULT, 5
mg/ kg (range: 4-6 mg/kg) daily, not to
exceed 400 mg daily; CHILD, 10 mg/kg
(range: 10-15 mg/kg) daily, not to
exceed 300 mg daily. (Refer to the DOH
National Tuberculosis Control Program).
NOTE: Patients at risk of developing peripheral
neuropathy as a result of malnutrition,
alcoholism or diabetes mellitus should
additionally receive pyridoxine, 10 mg
daily. Pregnant and patients with renal
failure should also receive pyridoxine
while on isoniazid therapy.
Dose Adjustment:
Renal Impairment:
For adult patients with creatinine clearance
<30 mL/minute or for adult patients
receiving hemodialysis: not to exceed
300 mg once daily, or 900 mg three
times per week. Prophylactic pyridoxine
recommended. Refer to the Tables in the
section on Recommended Treatment
Regimen for Tuberculosis.
Precautions:
WARNING: Severe and sometimes fatal
hepatitis may be associated with
isoniazid therapy which is age-related.
Very high doses can induce CNS adverse
effects (e.g., seizures, ataxia, stupor,
psychosis).
Malnutrition; chronic alcohol dependence;
diabetes mellitus and HIV infection (risk
of peripheral neuritis); elderly patients;
hepatic impairment (increased risk of
hepatotoxicity, monitor liver function
regularly, and frequently in the first 2
months); renal impairment (risk of
ototoxicity and peripheral neuropathy);
epilepsy (isoniazid may cause seizures;
ensure adequate control); slow
acetylator status (increased risk of
adverse effects); history of psychosis;
porphyria.
Pregnancy (not known to be harmful);
breastfeeding (monitor infant for
possible toxicity; theoretical risk of
convulsions and neuropathy);
Page | 195
ANTI-INFECTIVES
LIVER DISORDERS. Patients or their caregivers Avoid concomitant use with:
should be told how to recognize signs of Antacids (e.g., aluminum or magnesium
liver disorder, and advised to hydroxide) – these reduce the
discontinue treatment and seek absorption of isoniazid.
immediate medical attention if Diazepam – its metabolism may be inhibited by
symptoms such as nausea, vomiting, isoniazid.
malaise or jaundice develop. Ketoconazole – its metabolism may be
increased by isoniazid, thus decreasing
Adverse Drug Reactions: its antifungal effect.
Common: Acne, fever, GI disorders (e.g.,
nausea, vomiting, diarrhea), hepatitis, Administration: Absorbed best if taken on an
increased aminotransferases, raised empty stomach (1 hour before, or 2
antinuclear antibodies, rash, reduced hours after, a meal).
alertness, skin eruptions, tiredness.
Less Common: Atrophy, dryness of mouth, Pregnancy Category: C
optic neuritis, memory impairment,
peripheral neuritis, seizures, toxic
encephalopathy, toxic psychosis.
Rare: Agranulocytosis, amenorrhea, aplastic PYRAZINAMIDE
anemia, arthritic symptoms, Rx
convulsions, difficulty with micturition,
gynecomastia, hemolytic anemia,
hyperglycemia, hypersensitivity Oral: 500 mg tablet
reactions, lupus-like syndrome, 250 mg/5 mL and 500 mg/5 mL
pancreatitis, pellagra, pure red cell suspension,
aplasia, thrombocytopenia, urinary 120 mL
retention.
A nicotinamide-related bactericidal agent,
Drug Interactions: which is used in combination with other
Monitor closely with: drugs as first-line agents for treating
Carbamazepine – its metabolism is inhibited tuberculosis.
by isoniazid, thus increasing its
concentration and risk of toxicity Indications: Tuberculosis (especially in cases
(decrease dose if necessary). of allergy to a fixed-dose combination
Drugs increasing blood glucose concentration where a drug is introduced separately, or
(e.g., glucocorticoids, antipsychotics, in the presence of renal or hepatic
calcineurin inhibitors, and high-dose impairment); active against bacteria
thiazide diuretics) – their activity may be within macrophages.
affected by isoniazid (isoniazid can
decrease blood glucose concentration). NOTE: Bactericidal against M. tuberculosis in
Oral Contraceptives – few cases of acidic pH. Activity declines with time (pH
contraceptive failures reported. increases as inflammation decreases).
Paracetamol – potential toxicity of
Paracetamol when used with isoniazid Contraindications: Known hypersensitivity to
(more studies needed). pyrazinamide or any component of the
Phenytoin – its concentration is increased by formulation; severe hepatic impairment;
isoniazid, possibly increasing risk of porphyria; acute gout.
toxicity (decrease dose as required).
Rifampicin – increased risk of hepatotoxicity. Dose:
Tuberculosis, by mouth, ADULT, 25 mg/kg
(range: 20-30 mg/kg) daily, not to
exceed 2 g daily; CHILD, 30 mg/kg
(range: 20-40 mg/kg) daily, not to
Page | 196
ANTI-INFECTIVES
exceed 2 g daily. (Refer to the DOH
National Tuberculosis Control Program).
Dose Adjustments:
Renal Impairment:
For adult patients with creatinine clearance
<30 mL/minute or for adult patients
receiving hemodialysis: 25-35 mg/kg
per dose three times per week (not
daily ). Monitor for gout. Refer to the
Tables in the section on Recommended
Treatment Regimen for Tuberculosis.
Precautions:
Acute gout (it inhibits the renal excretion of
urate and raises uric acid
concentration); hepatic impairment
(monitor hepatic function: idiosyncratic
hepatotoxicity more common); renal
impairment; diabetes mellitus (monitor
blood glucose; may change suddenly).
Pregnancy (use it only if potential benefits
outweigh risks); and breastfeeding
(amount too small to be harmful).
LIVER DISORDERS. Patients or their caregivers
should be told how to recognize signs of
liver disorder, and advised to
discontinue treatment and seek
immediate medical attention if
symptoms, such as persistent nausea,
vomiting, malaise or jaundice, develop.
Adverse Drug Reactions:
Common: Hyperuricemia, nausea,
polyarthralgia, vomiting.
Less Common: Allergic reactions, anorexia,
diarrhea, fever, flushing, hepatotoxicity
(including hepatomegaly, jaundice, liver
tenderness, liver failure, malaise, and
splenomegaly), itch, rash, urticaria.
Rare: Acute gout, acute porphyric crisis,
dysuria, pellagra, photosensitivity,
sideroblastic anemia,
thrombocytopenia.
Drug Interactions:
Monitor closely with:
Anti-gout drugs (e.g., allopurinol, colchicine) –
pyrazinamide may increase serum uric
acid concentration and decrease the
efficacy of anti-gout therapy.
Rifampicin – pyrazinamide may enhance its
hepatotoxic effects (severe, or even
fatal, liver injury has been reported in
patients using these two drugs as a 2-
month treatment regimen for latent TB
infection).
Administration: Should be taken with food.
Pregnancy Category: C
RIFAMPICIN
Rx
Oral: 300 mg, 450 mg and 600 mg tablet/
capsule
200 mg/5 mL suspension, 120 mL
A rifamycin-derived bactericidal agent active
that is against gram-positive and gram-
negative cocci, some enteric bacteria,
mycobacteria and chlamydia, and is
used in combination with other drugs as
first-line agents for treating tuberculosis.
Indications: Tuberculosis (especially in cases
of allergy to a fixed-dose combination
where a drug is introduced separately, or
in the presence of renal or hepatic
impairment); leprosy.
Contraindications: Known hypersensitivity to
rifamycins, or any component of the
formulation; jaundice.
Dose:
Tuberculosis, by mouth, ADULT, 10 mg/kg
(range: 8-12 mg/kg) daily, not to exceed
600 mg daily; CHILD, 15 mg/kg (range:
10-20 mg/kg) daily, not to exceed 600
mg daily. (Refer to the DOH National
Tuberculosis Control Program).
Leprosy, see under Anti-Leprosy Medicines.
Dose Adjustments:
Renal Impairment:
Must not exceed recommended maximum
dose. (Refer to the DOH National
Tuberculosis Control Program).
Hepatic Impairment:
Page | 197
ANTI-INFECTIVES
Dose reduction is warranted (maximum, 8
mg/kg/day).
Precautions:
Monitor liver function and blood count in liver
disorders, alcohol dependency, the
elderly, and in prolonged therapy; daily
alcohol intake (may increase the risk of
drug-induced hepatotoxicity); renal
impairment; hepatic impairment
(impaired elimination; monitor liver
function); porphyria; it discolors soft
lenses.
Pregnancy (first trimester: very high doses are
teratogenic in animal studies; third
trimester: risk of neonatal bleeding may
be increased); and breastfeeding
(amount too small to be harmful; may
cause loose bowel actions in the baby).
IMPORTANT: Advise patient on hormonal
contraceptives to use additional means
(effectiveness is reduced); alternative
family planning advice should be
offered.
LIVER DISORDERS. Patients or their caregivers
should be told how to recognize signs of
liver disorders and advised to
discontinue treatment and seek
immediate medical attention if
symptoms such as persistent nausea,
vomiting, malaise, or jaundice develop.
NOTE: Resumption of rifampicin treatment
after a long interval may cause serious
immunological reactions, resulting in
renal impairment, hemolysis, or
thrombocytopenia – discontinue
permanently if serious adverse effects
occur.
Adverse Drug Reactions:
Common: Anorexia, cramps, diarrhea,
epigastric distress, flatulence, increased
hepatic enzymes, nausea, orange-red
coloration of body fluids (urine, tears,
saliva and sputum), pancreatitis, rash,
staining of soft contact lenses, vomiting.
Less Common: Ataxia, behavioral changes,
dizziness, edema, fatigue, flu-like
syndrome (characterized by fever, chills,
myalgia), flushing, headache, heartburn,
menstrual disturbances, numbness.
Page | 198
Rare: Acute renal failure, cerebral hemorrhage,
C. difficile-associated disease, collapse,
exfoliative dermatitis, hemolytic anemia,
hepatitis, jaundice, leukopenia,
myopathy, pemphigoid reactions,
psychosis, respiratory symptom, shock,
thrombocytopenic purpura, toxic
epidermal necrolysis.
Drug Interactions:
NOTE: Enzyme induction (See Appendix):
accelerates the metabolism of various
substrates, thus possibly decreasing
their effects.
Monitor closely with:
ACE inhibitors (e.g., captopril, enalapril) –
isolated reports of interaction with
rifampicin but minor clinical significance.
Analgesics – rifampicin increases clearance of
paracetamol, decreases levels of
diclofenac and opioids.
Anti-retroviral agents – levels of efavirenz,
ritonavir and nevirapine are decreased;
clearance of zidovudine is increased.
Anti-epileptics – levels of phenytoin and
valproic acid are reduced.
Azoles (e.g., ketoconazole) – their metabolism
is increased by rifampicin, thus
decreasing their antifungal effect.
Beta blockers (e.g., metoprolol, propranolol) –
their metabolism is increased by
rifampicin, thus decreasing their
concentration and reducing the clinical
effects.
Calcium channel blockers (e.g., Amlodipine) –
their levels are markedly reduced by
rifampicin.
Corticosteroids (e.g., hydrocortisone,
prednisone and prednisolone) – their
metabolism is increased by rifampicin,
possibly reducing their activity.
Cotrimoxazole – when used for prophylaxis in a
HIV-positive patient, its concentration
and efficacy may be decreased by
rifampicin.
Digoxin – possible reduction in the plasma
concentration of digoxin, reducing the
clinical effects.
Doxycycline – possible reduction in the plasma
concentration of doxycycline, reducing
the effects.
ANTI-INFECTIVES
Theophylline – its concentration and
therapeutic effects are decreased by
rifampicin.
Thyroid hormones (e.g., thyroxine) – rifampicin
may accelerate its metabolism (this may
increase thyroxine requirements in a
state of hypothyroidism).
Avoid concomitant use with:
Antacids (e.g., aluminum and magnesium
hydroxide) – these may reduce the
absorption of rifampicin.
Contraceptives, Oral – accelerated metabolism
of estrogens and progestogens, reducing
the contraceptive effect.
Praziquantel – its metabolism is increased by
rifampicin, reducing its concentration to
ineffective levels.
Administration: Take dose at least 30 minutes
before a meal (absorption is reduced
when taken with food).
Pregnancy Category: C
FIXED-DOSE FORMULATIONS
ISONIAZID + RIFAMPICIN
Rx
Oral: 75 mg Isoniazid + 150 mg Rifampicin
tablet
A fixed combination of isoniazid and rifampicin,
which is used for treating tuberculosis
and serves as an aid to patient
compliance.
Indication: Tuberculosis.
Contraindications: Combined preparations
may not be suitable for use in children;
see under Single Dose Formulation:
Isoniazid and Rifampicin.
Dose:
Tuberculosis, by mouth, ADULT, refer to the
DOH National Tuberculosis Control
Program.
Dose Adjustments, Precautions, Adverse Drug
Reactions, and Drug Interactions: See
under Single Dose Formulation:
Isoniazid and Rifampicin for other
information.
Administration: Take on an empty stomach
with full glass of water.
Pregnancy Category: C
ISONIAZID + RIFAMPICIN +
Rx ETHAMBUTOL
Oral: 75 mg isoniazid + 150 mg Rifampicin +
275 Ethambutol mg tablet
A fixed combination of isoniazid, rifampicin and
ethambutol, which offers ease of
administration and facilitates patient
compliance in the treatment of
tuberculosis.
Indication: Tuberculosis.
Contraindications: Combined preparations
may not be suitable for use in children;
see under Single Dose Formulation:
Isoniazid, Rifampicin and Ethambutol.
Dose:
Tuberculosis, by mouth, ADULT, refer to the
DOH National Tuberculosis Control
Program.
Dose Adjustments, Precautions, Adverse Drug
Reactions, and Drug Interactions: See
under Single Dose Formulation:
Isoniazid, Rifampicin and Ethambutol
Administration: Take on an empty stomach
with full glass of water.
Pregnancy Category: C
Oral: 75 mg Isoniazid + 150 mg Rifampicin +
400 mg Pyrazinamide + 275 mg
Ethambutol tablet
Page | 199
ANTI-INFECTIVES
ISONIAZID + RIFAMPICIN
R + PYRAZINAMIDE +
x ETHAMBUTOL
A fixed combination of isoniazid, rifampicin,
pyrazinamide and ethambutol, which
offers ease of administration and
facilitates patient compliance in the
treatment of tuberculosis.
Indication: Tuberculosis.
Contraindications: Combined preparations
may not be suitable for use in children;
see under Single Dose Formulation:
Ethambutol, Isoniazid, Pyrazinamide
and Rifampicin.
Dose:
Tuberculosis, by mouth, ADULT, refer to the
DOH National Tuberculosis Control
Program.
Dose Adjustments:
Renal and Hepatic Impairment:
For severe impairment, dose reduction may be
warranted.
Precautions, Adverse Drug Reactions, and
Drug Interactions: See under
Ethambutol, Isoniazid, Pyrazinamide,
and Rifampicin.
Administration: Should be taken on an empty
stomach; take 1 hour before, or 2 hours
after, meals.
Pregnancy Category: C
Page | 200
ANTI-LEPROSY
CLOFAZIMINE
Rx
Oral: 50 mg and 100 mg capsule
A phenazine dye, which preferentially binds to
mycobacterial DNA at the guanine base
to inhibit its growth; given for sulfone-
resistant leprosy.
Indications: Multibacillary leprosy; type 2 lepra
reactions (Erythema Nodosum
Leprosum).
Contraindication: Known hypersensitivity to
clofazimine or any component of the
formulation.
Dose:
Multibacillary leprosy (in combination with
dapsone and rifampicin), by mouth,
ADULT, 50 mg once daily, and 300 mg
once a month; CHILD 10-14 years, 50
mg on alternate days, and 150 mg once
a month; CHILD <10 years, requires
appropriate dosage adjustments (e.g.,
50 mg twice a week and, 100 mg once a
month); continue treatment for 12
months.
Type 2 lepra reactions, by mouth, ADULT and
CHILD, 200-300 mg daily in 2 or 3
divided doses for a maximum of 3
months; 4-6 weeks treatment may be
required before any effect is seen.
Refer to the Tables from the 2016 DOH
National Leprosy Control Programme
Manual of Procedures.
Dose Adjustments:
Renal and Hepatic Impairment:
Use drug with caution for mild-to-moderate
impairment; for severe impairment, the
patient should be referred to a specialist.
Precautions:
Patients with pre-existing GI symptoms and
problems (reduce the dose, increase the
dose interval or discontinue if symptoms
ANTI-INFECTIVES
develop during treatment); avoid use if
abdominal pain and diarrhea persist; DAPSONE
renal impairment; hepatic impairment; Rx
may discolor soft contact lenses; avoid
treatment with daily doses exceeding
Oral: 100 mg tablet
100 mg.
Pregnancy (use with caution during first
A sulfonamide with a broad spectrum of activity
trimester); breastfeeding (crosses
against many bacteria, but is mainly
placental barrier and excreted in breast
used for its antileprosy properties of
milk; can cause reversible skin
which it is bacteriostatic; competitively
discoloration in nursing infant).
inhibits paraaminobenzoic acid and folic
acid synthesis.
Adverse Drug Reactions:
Common: Abdominal pain, conjunctival
Indications: Paucibacillary and multibacillary
discoloration, diarrhea, dryness of skin,
leprosy; dermatitis herpetiformis.
eye irritation, ichthyosis, itch, nausea,
pink to brownish-black discoloration of
Contraindications: Known hypersensitivity to
skin, rash, red-brown coloration of body
dapsone, sulfonamides, and sulfones, or
fluids, vomiting.
any component of the formulation;
Less Common: Constipation, dizziness,
severe anemia; porphyria.
drowsiness, eosinophilic enteritis, GI
bleeding, splenic infarction, taste
Dose:
disturbance.
Dermatitis herpetiformis, by mouth, ADULT,
Rare: Enteropathy (due to the deposition of
start at 50 mg daily, increase to 300 mg
clofazimine crystals in the GI mucosa
daily (or higher to achieve full control).
and lymph nodes), phototoxicity.
NOTE: reduce dosage to minimum level
as soon as possible.
Drug Interactions:
Multibacillary leprosy (in combination with
Monitor closely with:
rifampicin and clofazimine), by mouth,
Isoniazid – this increases the plasma and
continued for 12 months, ADULT, 100
urinary concentration of clofazimine;
mg daily; CHILD 10-14 years old, 50 mg
decreases its skin concentration.
daily; CHILD <10 years old, 50 mg every
Rifampicin – its rate of absorption may be
other day.
decreased by clofazimine, possibly
Paucibacillary leprosy (in combination with
increasing the time to peak plasma level.
rifampicin), by mouth, continued for 6
months, ADULT, 100 mg daily; CHILD 10-
Avoid concomitant use with:
14 years old, 50 mg daily; CHILD <10
Dapsone – this may reduce the anti-
years old, 50 mg every other day.
inflammatory effect of clofazimine for
Refer to the Tables from the 2016 DOH
Lepra type 2 reactions.
National Leprosy Control Programme
Manual of Procedures.
Administration: Medicines used in the
treatment of leprosy should always be
Dose Adjustments:
used in combination (essential to
Renal and Hepatic Impairment:
prevent the emergence of resistance);
Use drug with caution for mild to moderate
Clofazimine is best absorbed when given
impairment; for severe impairment, the
right after a meal.
patient should be referred to a specialist.
Pregnancy Category: C
Precautions:
Sulfonamide allergy (may predispose to
dapsone allergy; begin with low dose of
dapsone and monitor closely for adverse

Page | 201
ANTI-INFECTIVES
effects); cardiopulmonary disease or HIV
and PCP (tolerate hemolytic anemia and
methemoglobinemia poorly); anemia
(treat severe anemia before the
commencement of therapy and monitor
blood counts during treatment; dapsone
causes hemolytic anemia and
methemoglobinemia); susceptibility to
hemolysis, including G6PD deficiency, or
in patients receiving drugs capable of
inducing hemolysis (including
breastfeeding affected infants);
hemoglobin M deficiency;
methemoglobin reductase deficiency; in
patients with hepatic or renal disease;
dermatologic reactions (serious
reactions are rare, but potentially
occurring); peripheral neuropathy (motor
loss and muscle weakness have been
reported with use); prolonged use may
result in fungal or bacterial
superinfection.
Pregnancy (supplementation with folic acid
may be necessary if use is warranted;
possible risk of hyperbilirubinemia in
neonates); breastfeeding (avoid use;
dapsone is excreted in substantial
amounts in breast milk).
BLOOD DISORDERS. On long-term treatment,
patients and their caregivers should be
told how to recognize blood disorders,
and advised to seek immediate medical
attention if symptoms, such as fever,
sore throat, rash, mouth ulcers, purpura,
bruising, or bleeding develop.
Adverse Drug Reactions:
Common: Asymptomatic methemoglobinemia,
GI symptoms, hemolytic anemia (occurs
in most patients taking more than 200
mg daily); rash (in HIV patients).
Less Common: Allergy, anorexia, fever,
headache, insomnia, nausea,
nervousness, vomiting.
Rare: Agranulocytosis, albuminuria, aplastic
anemia, blurred vision, Dapsone
syndrome (resembling mononucleosis),
hepatitis, Jarisch-Herxheimer reactions,
neutropenia, paresthesia, peripheral
neuropathy (with doses more than 200
mg daily); psychosis, severe skin
reactions (e.g., exfoliative dermatitis).
Page | 202
Drug Interactions:
Monitor closely with:
Cotrimoxazole – plasma concentration of both
dapsone and cotrimoxazole may
increase with concomitant use.
Rifampicin – this may reduce plasma dapsone
concentration.
Avoid concomitant use with:
Antimalarial agents (chloroquine and/or
primaquine) – these may enhance the
toxic effect; concomitant use of these
drugs with dapsone may increase the
risk of hemolytic reactions.
Clofazimine – its anti-inflammatory effect for
Lepra type 2 reactions may be reduced
by dapsone.
Administration: This may be administered with
meals if GI upset occurs; do not
administer with antacids, alkaline foods,
or drugs.
NOTE: Stop dapsone if a serious skin reaction
or muscle weakness occurs.
Pregnancy Category: C
RIFAMPICIN
Rx
Oral: 300 mg, 450 mg and 600 mg tablet/
capsule
200 mg/5 mL suspension, 120 mL
A rifamycin-derived bactericidal agent active
that is against gram-positive and gram-
negative cocci, some enteric bacteria,
mycobacteria and chlamydia.
Indication: Leprosy (paucibacillary and
multibacillary).
Contraindications: See under Antituberculosis.
Dose:
Multibacillary leprosy, by mouth, ADULT, 50-70
kg, 600 mg once a month with dapsone
(100 mg/day) and clofazimine (50
mg/day + 300 mg /month) under
ANTI-INFECTIVES
supervision; Duration of treatment: > 2
years, and when monitoring is feasible,
until skin smears are negative.
Paucibacillary leprosy, by mouth, ADULT, 50-
70 kg, 600 mg once a month with
dapsone (1oo mg/day); Duration of
treatment: > 6 months.
Refer to the Tables from the 2016 DOH
National Leprosy Control Programme
Manual of Procedures.
See under Antituberculosis for other
therapeutic information.
ANTIVIRALS
ACICLOVIR/ACYCLOVIR
Rx
Oral: 200 mg, 400 mg and 800 mg tablet
200 mg/5 mL suspension, 60 and 120
mL
An acyclic, purine nucleoside analogue, which
has a high degree of specificity, and is
active against herpes simplex virus and
varicella-zoster virus.
Indications: Initial treatment and prophylaxis of
recurrent mucosal and cutaneous
herpes (HSV1, HSV2) infections; acute
chickenpox (Varicella zoster) in
immunocompromised patients; herpes
zoster infections (shingles).
Contraindications: Known hypersensitivity to
aciclovir, valaciclovir, or any other
components of the formulation; serious
adverse reactions to individual drug or
metabolite; should not be used to treat
severe HSV infections in children with
low resistance to disease.
Dose:
Treatment of initial infection of genital herpes
simplex, by mouth, ADULT, 400 mg 3
times daily for 5-7 days; CHILD >2 years,
40-80 mg/kg/ day in 3-4 divided doses,
usually for 5 days (longer if new lesions
appear during treatment or if healing is
incomplete; CHILD <2 years, half the
adult dose.
Treatment of recurrent infection of genital
herpes simplex, by mouth, ADULT, 400
mg 3 times daily (or 800 mg twice daily)
for 5 days; or 800 mg 3 times daily for 2
days.
Prevention of genital herpes simplex, HIV-
positive, by mouth, ADULT, 400-800 mg
2 or 3 times daily.
Prevention of recurrent herpes simplex, by
mouth, ADULT, 200 mg 4 times daily or
400 mg twice daily, reduced to 200 mg
2-3 times daily if possible and
interrupted every 6-12 months for
reassessment.
Prophylaxis of herpes simplex in the
immunocompromised, by mouth, ADULT
and CHILD >2 years or >40 kg, 20
mg/kg/ dose 4 times a day for 5 days or
200-400 mg 4 times daily; CHILD <2
years, half of the adult dose.
Treatment of chickenpox (Varicella-zoster or
VZV), by mouth, in immunocompetent
hosts, ADULT, 800 mg 4-5 times daily for
5-7 days; CHILD >2 years old, at risk of
having moderate to severe varicella,
chronic cutaneous or pulmonary
disease, 80 mg/kg/day divided in 4
doses per day (maximum dose, 3.2
g/day) to start within 24 hours of rash, to
be given for 5 days.
NOTE: In immunocompetent children 2-
12 years of age, with mild to moderate
disease, no treatment needed,
Treatment of herpes zoster, by mouth, in
immunocompetent ADULT, 800 mg 5
times daily for 7-10 days.
NOTE: Therapy should be initiated as soon as
possible after a diagnosis of chickenpox
or herpes zoster, or at the first sign or
symptoms of an outbreak of genital
herpes.
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
In obese patients, parenteral dose
should be calculated on the basis of
ideal weight for height (to avoid
excessive dosage).
Page | 203
ANTI-INFECTIVES
Dose Adjustment:
Renal impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: May aggravate renal insufficiency
due to intratubular obstruction with
aciclovir microcrystals.
Use with caution in patients with dehydration,
renal disease, electrolyte abnormalities,
underlying neurologic diseases or
hepatic dysfunction; maintain adequate
hydration (especially with infusion or
high doses, or during renal impairment)
to minimize renal adverse effects
(crystals may precipitate in renal tubules
and impair renal function); renal
impairment (increased risk of
nephrotoxicity and neurological adverse
effects);
Suppressive therapy of genital herpes should
be considered only if patient is severely
affected (periodic evaluation is
recommended); and cross-resistance
may occur between agents due to their
similar mechanisms of action and
activation pathways.
Prolonged or repeated courses of aciclovir in
severely immunocompromised patients
may result in selection of resistant
viruses associated with infections which
may not respond;
The elderly (at increased risk of neurological
adverse effects; likely to have reduced
renal function); pediatrics (safety and
effectiveness in children <2 years of age
have not been adequately studied).
Pregnancy (not known to be harmful; use only
when potential benefit outweighs risk);
breastfeeding (significant amount found
in milk after systemic administration; not
known to be harmful).
Adverse Drug Reactions:
Common: Diarrhea, hallucinations (high dose),
headache, nausea, vomiting.
Page | 204
Less Common: Abdominal pain, agitation,
arthralgia, confusion, constipation,
dizziness, drowsiness, edema, fatigue,
pruritus, photosensitivity, rash, renal
impairment, sore throat, urticaria,
vertigo, weakness.
Rare: Acute renal failure, anaphylaxis, anemia,
anorexia, coma, crystalluria, dyspnea,
fatigue, fever, hepatitis, jaundice,
leukopenia, neutropenia, psychosis,
seizures, Stevens-Johnson syndrome,
thrombocytopenia, toxic epidermal
necrolysis, tremor.
Drug Interactions:
Monitor closely with:
Probenecid – this increases the half-life and
AUC of aciclovir.
Theophylline – aciclovir may increase its
concentration and risk of adverse
effects.
Zidovudine – increased effect of aciclovir.
Avoid concomitant use with:
Zoster Vaccine – its therapeutic effect may be
diminished by aciclovir.
Administration: For dosage taken 5 times daily,
take every 4 hours during waking hours.
Make sure that the patient drinks plenty
of fluids (at least 1.5-2 L daily). This
medication may make the patient feel
dizzy or confused; advise not to drive or
operate machinery if the patient is
affected.
Pregnancy Category: B
OSELTAMIVIR
Rx
Oral: 75 mg capsule (as phosphate)
This inhibits influenza virus neuraminidase,
resulting in the inability of the virus to
spread in the respiratory tract. It is active
against both Influenza A and B. It inhibits
amantadine- and rimantadine-resistant
influenza A virus.
ANTI-INFECTIVES
Indications: Prophylaxis of influenza A and B
(not a substitute for flu vaccination);
treatment of uncomplicated acute
illness due to influenza A and B infection
in patients who have been symptomatic
for no more than 2 days.
Contraindication: Known hypersensitivity to
oseltamivir or any component, or other
sialic acid-based neuraminidase
inhibitor.
Dose:
Post-exposure prophylaxis of influenza (should
be given within 2 days of exposure), by
mouth, ADULT, 75 mg/dose twice a day
for at least 7 days or for up to 6 weeks
during community outbreaks or
epidemics; CHILD >12 years, 75 mg
twice daily; CHILD >1-12 years, if <15 kg,
give 2 mg/kg/dose twice daily,
(maximum, 30 mg/dose); if >15-23 kg,
give 45 mg/dose twice a day; if >23-40
kg, give 60 mg/dose twice a day; if >40
kg, give 75 mg/dose twice a day, with
these doses given for at least 7 days or
for up to 6 weeks during epidemics..
Treatment of influenza (must be given within 2
days of onset of flu symptoms), by
mouth, ADULT, 75 mg every 12 hours for
5 days; CHILD >12 years, 75 mg twice
daily for 5 days; CHILD >1-12 years, if
<15 kg, give 2 mg/kg/dose twice daily
for 5 days, (maximum, 30 mg/dose); if
>15-23 kg, give 45 mg/dose twice a day
for 5 days; if >23-40 kg, give 60
mg/dose twice a day for 5 days; if >40
kg, give 75 mg/dose twice a day for 5
days.
Dose Adjustments:
Renal impairment:
Administer with caution in moderate to severe
renal impairment.
Precautions:
Warning: Severe hypersensitivity
reactions have been associated with use.
Most effective when used within 24-48 hours
of onset of symptoms.
Age <1 year: safety and efficacy for prophylaxis
of influenza has not been established.
Age <2 weeks: safety and efficacy for
treatment of influenza has not been
established.
Increased risk of serious skin reactions.
Reports of potentially fatal neuropsychiatric
adverse events in patients with flu.
Adverse Drug Interactions:
Common: Abdominal pain, conjunctivitis, ear
disorder, epistaxis, insomnia, nausea,
vomiting, vertigo.
Less common: Aggravation of diabetes,
anemia, arrhythmia, confusion, delirium,
hemorrhagic colitis, hepatitis, humerus
fracture, peritonsillar abscess,
pneumonia, pseudomembranous colitis,
pyrexia, rash, seizure, increased
transaminase, toxic epidermal
necrolysis, unstable angina, swelling of
face or tongue. Hypothermia also
reported.
Drug Interactions:
Monitor drug closely with:
Clopidogrel – this decreases levels of
oseltamivir.
Probenecid – this increases levels of
oseltamivir, resulting in a 2-fold increase
in exposure to oseltamivir carboxylate
(active metabolite).
Administration:
May be taken with meals to reduce GI side
effects. Capsule may be opened and
mixed with sweetened food products.
To prepare 100 mL of 6 mg/mL suspension,
put 7 mL of distilled water into a glass or
polyethylene terephthalate (PET) bottle
then empty contents of eight 75 mg
capsules (= 600 mg) into the bottle. Swirl
the suspension for at least 2 minutes
then slowly add 91 mL of syrup,
sweetened condensed milk, or yogurt.
Shake well for 30 minutes. Instruct
patient to shake mixture well before
using. Swallow mixture immediately
after preparation. Suspension can
remain stable for 5 days at room
temperature or 5 weeks if refrigerated at
2-8 degrees centigrade.
Page | 205
ANTI-INFECTIVES
Pregnancy Category: C
ATC Code: J05AH02
IMMUNE SERA AND
IMMUNOGLOBULINS
ANTI-RABIES SERUM
Rx
Inj.: 200 IU/mL, 5 mL vial (IM)
400 IU/mL, 5 mL vial (IM)
A sterile, non-pyrogenic preparation which
consists of F(ab’)2 fragments of equine
antirabies immunoglobulin of not less
than 200 IU/mL
Indication:
For the seroprophylaxis of rabies in individuals
who are suspected to have been
exposed to the rabies virus, when rabies
immunoglobulin (human) is unavailable
or unaffordable.
Contraindications:
Known hypersensitivity to products prepared
from horse serum, or any other
component within the serum; Not for IV
administration.
Dose:
Prophylaxis in individuals suspected to have
been exposed to the rabies virus, by
infiltration, ADULT and CHILD, 40 IU/kg
of body weight in and around the
cleansed wound. If infiltration of whole
volume is not possible, give the
remainder by IM injection slowly.
(Wounds in certain anatomical sites,
such as fingertips, should be infiltrated
with care so as to prevent a local
increase in pressure in the tissue).
NOTE: When the volume required to infiltrate
the wound(s) exceeds the recommended
dose, some clinicians recommend
Page | 206
diluting the calculated dose in saline to
yield a two- to-threefold increase in
solution volume to ensure that all wound
areas receive adequate infiltration.
Dose Adjustments: No information found.
Precautions:
Do not administer intravenously (due to a risk
of shock); ensure that the needle has not
penetrated a blood vessel; do not give
repeated doses once rabies vaccine is
given as this may reduce the
immunologic response to the vaccine.
Despite the high degree of purification of the
serum, a skin test is recommended
before administering rabies antiserum
(to determine possible allergic
symptoms to horse proteins).
If the recommended dosage is not strictly
observed (e.g., overdosage), there is a
risk of immunosuppressive interference
with rabies vaccine.
In patients with a history of bleeding disorders,
including thrombocytopenia, and
patients on anticoagulant therapy
(bleeding/ hematoma may occur from
IM administration).
NOTE: Immunoglobulins may interfere with the
immune response to live virus vaccines.
Adverse Drug Reactions:
Common: Acute febrile reaction, injection site
swelling and pain, serum sickness-like
re-actions.
Rare: Anaphylaxis.
Drug Interaction:
Avoid concomitant use with:
Corticosteroids – these may attenuate the
immune response to the anti-rabies
serum.
Vaccines (Live, attenuated virus) –
immunoglobulin administration may
interfere with the development of
immune response to vaccines.
Administration: Administer as soon as
possible, at the same time as the rabies
vaccine, or up to 7 days after vaccine
injection; the remaining serum should be
ANTI-INFECTIVES
administered via the IM route (into the
gluteal region) in a single injection
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
ANTI-TETANUS SERUM
Rx
Inj.: 4,000 IU/mL, 2.5 mL vial/ampul (IM)
1,500 IU/0.7 mL solution for injection,
vial and ampul (IM)
1,500 IU/mL, 1 mL and 1.5 mL
vial/ampul (IM)
A sterile, nonpyrogenic preparation obtained
from the fractionation of serum of
horses, which have been immunized
against tetanus toxin, and contains the
specific antitoxin globulins that may
neutralize the toxin formed by
Clostridium tetani.
Indications: Prophylaxis against tetanus in non-
immune individuals after serious injury
or bite when tetanus immunoglobulin
(human) is unavailable or unaffordable;
treatment of tetanus when tetanus
immunoglobulin is unavailable or
unaffordable.
Contraindications: Known hypersensitivity to
tetanus antitoxin or any other
component within the serum, and any
product prepared from horse serum.
Dose:
Post-exposure prophylaxis against tetanus, by
IM injection, 3,000-5,000 IU.
Treatment of tetanus infection, by IM injection,
ADULT and CHILD, 50,000-100,000 IU
single dose; NEWBORN, 500 units/kg or
5,000-10,000 IU in tetanus
neonatorum.
NOTE: The above doses could be given ½ IV and the
rest IM, after appropriate testing for sensitivity
and desensitization, if necessary.
Dose Adjustments: No information found.
Precautions:
WARNING: Increased risk of fatal anaphylaxis in
hypersensitive individuals.
Informed consent and skin test are required (a
negative skin or eye test is not an
absolute indication of the absence of
sensitivity); a syringe with 0.3 mL of
1:1000 aqueous solution of epinephrine
should be always at hand.
NOTE: Immunoglobulins may interfere with the
immune response to live virus vaccines which
should normally be given either at least 3
weeks before or at 3 months after
administration of an immunoglobulin.
Adverse Drug Reactions:
Common: Acute febrile reaction, injection site
swelling and pain, serum sickness-like
reactions.
Rare: Anaphylaxis.
Drug Interaction:
Avoid concomitant use with:
Vaccines (Live, attenuated virus) –
immunoglobulin administration may
interfere with the development of
immune response to vaccines.
Administration: The serum should be
administered via the IM route. If a large
volume is required, it is recommended to
administer the serum in divided doses at
different sites.
NOTE: Vaccines should be stored within the safe
temperature range of 2-8°C. Freezing is the
most common cause of vaccine damage; do not
use a defrosted vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
COBRA ANTIVENIN
Rx
Inj.: 800 IU/4.8 mL, 1 mL ampule (for IV
infusion)
A monovalent purified fraction of
immunoglobulin fragments from the
plasma of animals immunized against a
Page | 207
ANTI-INFECTIVES
snake venom or a snake venom mixture;
its use is limited to a few closely-related
species whose venoms show clinically
effective cross-neutralization.
Indications: Management of patients with Naja
spp. envenomations (e.g., N.
philippinensis, N. samarensis and N.
sumatrana); signs of neurotoxicity or
swelling involving more than half the
bitten extremity.
Contraindications: Allergy to horse-based
products, or antivenin by history or as a
result of an appropriate sensitivity test;
hypersensitivity to any component of the
formulation, including papaya or papain;
cross allergenicity with dust mite and
latex allergens.
Dose:
Naja spp. envenomations, ADULT and CHILD,
usual dose is 0.5 mL IM. But in severe
cases: initial dose of 5-10 vials IV is given
and repeated every 1-2 hours until local
manifestations, coagulation tests, and
systemic signs are observed to be
normal. The antivenin can be diluted in
500 mL isotonic fluid to run for 1-2
hours, or given undiluted IV over 10-15
minutes.
NOTE: Begin infusion slowly, watching carefully
for adverse effects. Stop the infusion
temporarily if these occur. If there is no
adverse reaction, increase the rate,
aiming to give the entire infusion over
about 15-20 minutes.
Precautions:
WARNING: Antivenins should never be
administered prophylactically to
asymptomatic patients. Pain and
fang marks are not intrinsically signs
of envenomation.
Patients sensitive to antivenin or horse serum
may develop anaphylaxis. Prior to IV or
IM antivenin administration, proper skin
test should be performed and
interpreted (therapy may be modified if
indicated).
Page | 208
In life threatening situations, pre-treat with
antihistamine (diphenhydramine, 50-
100 mg IV), followed by slow IV infusion
of very dilute antivenin. At the first sign
of hypersensitivity reaction, stop infusion
and administer subcutaneously 0.5-1.0
mL epinephrine (1:1000).
Pre-existing renal, hepatic, cardiac, or
respiratory treatment with anticoagulant
or antiplatelet drugs (increased risk of
serious outcomes, including death, from
snakebite); the elderly (may require
more vigorous treatment); children
(should not be given weight-adjusted
doses; the amount required depends on
the amount of venom to be neutralized).
Refer to Interim Practice Guidelines in
Common Poisoning for further
information.
STORAGE. Cold-chain management in
hospitals/ health facilities.
Adverse Drug Reactions:
Common: Anaphylaxis or anaphylactoid
reactions, chest discomfort, chills,
dizziness, dyspnea, edema of the face,
tongue, and throat, fever, flushing,
headache, hypotension, pruritus, rash,
serum sickness, tachypnea, urticaria.
Less Common: Abdominal pain, angioedema,
arthralgia, bradycardia, bronchospasm,
collapse, myalgia, nausea, neurological
impairment, pain at the infusion site,
sweating, tachycardia, vertigo, vomiting,
wheezing.
Rare: Cardiac arrest; encephalitis
Drug Interactions: No information found.
Administration: The treatment should begin as
soon as possible and preferably within 4-
6 hours of envenomation; monitor for 1
hour following the infusion.
The SC or IM administration is preferred.
Administer by IV only when symptoms of
poisoning are evident.
Management of the Snake Bite:
1. The cobra antivenin is most effective
when injected immediately after the
bite. When possible, test for
sensitivity to horse serum prior to
ANTI-INFECTIVES
administration (see Precautions
above).
2. Kill and keep the snake responsible
for the bite, whenever possible, to
identify the specific venom.
3. Apply a tourniquet immediately above
the bite. It should be tight enough to
impede venous and lymph flow to and
from the bitten part but allows a
finger to be inserted under it. Loosen
tourniquet every 15 minutes for 15–
30 seconds to allow blood flow.
4. If done immediately or shortly after
the bite, make short deep incisions
(¼ to ½ inch long and ½ inch deep)
over the site of the bite through the
fang marks under aseptic conditions.
Avoid principal blood vessels.
5. Suction the blood with the mouth or
with a mechanical device to draw out
the poison. If done using the mouth,
make sure there are no open lesions
on the mucous membrane. Rinse
mouth with a mild solution of
potassium permanganate or water.
6. Inject part of the antivenin into the
site of the bite and around it if done
soon after. Inject most of the
antivenin above the tourniquet, then
slowly release the tourniquet.
7. Administer saline, plasma, or blood to
combat shock. Antibiotics and
antitoxins may be needed for
infections commonly associated with
snakebites. Antihistamines may be
necessary to control manifestations
of allergy.
8. Patient should remain lying down. Do
NOT allow to patient to walk or run
around, become overheated, or take
alcohol stimulants as these hasten
blood flow.
9. Black coffee or strong tea may be
given to combat weakness or
giddiness.
10. Do NOT cauterize the wound with
strong acid, potassium
permanganate or heat.
Pregnancy Category: C
RABIES
Rx IMMUNOGLOBULIN
(HUMAN)- HRIG
Inj.: 150 IU/mL, 2 mL and 5 mL vial (IM)
150 IU/mL, 2 mL and 5 mL and 10 mL
(IM)
Human rabies immunoglobulin is a preparation
containing immunoglobulins derived
from the plasma of adult humans
immunized with rabies vaccine, which is
used as part of the management of
potential rabies (passive immunity)
following exposure of an unimmunized
individual to a suspected animal.
Indication:
Passive immunization, either post-exposure or
in suspected exposure, to rabies in
unimmunized individuals (in conjunction
with rabies vaccine).
NOTE: The Guidelines in the 2012 National
Rabies Prevention and Control Program
recommend that Rabies
Immunoglobulin be given, in conjunction
with rabies vaccine, to patients with
Category III Exposure that includes:
a. Transdermal bites (puncture wounds,
lacerations, avulsions) or
scratches/abrasions with
spontaneous bleeding;
b. Licks on broken skin or mucous
membrane;
c. Exposure to a rabies patient through
bites, contamination of mucous
membranes (eyes, oral/nasal
mucosa, genital/anal mucous
membrane) or open skin lesions with
body fluids through splattering and
mouth-to-mouth resuscitation;
d. Unprotected handling of infected
carcass;
e. Ingestion of raw infected meat;
f. Exposure to bats; and
g. All Category II exposures on head and
neck areas.
Page | 209
ANTI-INFECTIVES
Situations where HRIG is preferred are: history
of hypersensitivity to equine sera;
multiple severe exposures especially
where the dog is sick or suspected of
being rabid; and symptomatic HIV
infected patient.
Contraindications: Avoid repeat doses after
vaccine treatment is initiated; not for
intravenous administration
NOTE: Documentation of allergenic cross-
reactivity for immunoglobulins is limited.
However, because of similarities in
chemical structure and/or
pharmacologic actions, the possibility of
cross-sensitivity cannot be ruled out with
certainty.
Dose:
Passive immunization against rabies (post-
exposure or following suspected
exposure), by local wound infiltration,
ADULT and CHILD, 20 IU/kg (in a single-
dose) in and around the cleansed
wound; if wound is not visible or has
healed, or if infiltration of whole volume
is not possible, give remainder by IM
injection at a site distant from the
vaccine administration site (should
always be administered as part of rabies
vaccine regimen).
NOTE: If rabies vaccine was initiated without
rabies immunoglobulin, rabies
immunoglobulin may be administered
through the seventh day after the
administration of the first dose of the
vaccine (day 0). Administration of
immunoglobulin is not recommended
after the seventh day post vaccine since
an antibody response to the vaccine is
expected during this time period.
Precautions:
Anaphylaxis or hypersensitivity reactions
(hypersensitivity and anaphylactic
reactions, although rare, can occur);
NOTE: immediate treatment, including
epinephrine 1:1000, should be
available) - for treatment of anaphylaxis,
see Adverse Reactions.
Page | 210
In patients with isolated immunoglobulin A
deficiency or a history of systemic
hypersensitivity to human
immunoglobulins.
In patients with a history of bleeding disorders,
including thrombocytopenia, and
patients on anticoagulant therapy
(bleeding/ hematoma may occur from IM
administration).
A single dose is recommended; repeating the
dose may interfere with maximum active
immunity expected from the vaccine.
Immunoglobulins may interfere with the
immune response to live virus vaccines
which should normally be given either at
least 3 weeks before or at least 3
months after administration of an
immunoglobulin.
Pregnancy (however, pre-exposure prophylaxis
may be indicated if the risk for exposure
to rabies is significant).
Administer RIG in conjunction with rabies
vaccine.
NOTE: Not recommended for use in patients
with a history of pre-exposure
vaccination or post-exposure prophylaxis
with human diploid cell vaccine (HDCV),
purified chick embryo cell vaccine, or
rabies vaccine adsorbed, or previous
vaccination with any other rabies
vaccine and documentation of antibody
response.
Adverse Reactions:
Common: Acute febrile reaction, injection site
swelling and pain, serum sickness-like
reactions.
Rare: Anaphylaxis, nephrotic syndrome.
Treatment of anaphylaxis:
Give epinephrine 0.5 mL of 0.1 per cent
solution (1 in 1000, 1 mg/mL) for adults
and adolescents; and 0.01 mL/kg body
weight for children, injected
subcutaneously or IM.
Drug Interaction:
Avoid concomitant use with:
Vaccines (Live, attenuated virus) –
immunoglobulin administration may
ANTI-INFECTIVES
interfere with the development of
immune response to vaccines.
Live virus vaccines should normally be
given either at least 3 weeks before or at
least 3 months after administration of an
immunoglobulin.
Administration: If anatomically feasible, the full
rabies immunoglobulin dose should be
infiltrated around and into the wound(s),
even if the wound has healed. Any
remaining amount should be
administered deep IM at a site distant
from the vaccine administration site
(e.g., deltoid muscle of the upper arm or
lateral thigh muscle). The gluteal area
should be avoided to reduce the risk of
sciatic nerve damage. Do not administer
rabies vaccine in the same syringe or at
the same administration site as RIG.
WITH RABIES VACCINE. If schedule requires
rabies vaccine and rabies
immunoglobulin to be administered at
the same time, they should be
administered using separate syringes
and at separate sites. If RIG and the
rabies vaccine cannot be given on the
same day, the vaccine should be given
before RIG because the latter inhibits
production of neutralizing antibodies
induced by vaccination.
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C Unknown or
less than 3
250 IU/mL, 1 mL pre-filled syringe (IM)
250 units/mL, 1 mL and 2 mL vial (IM)
A sterile preparation of globulins derived from
the plasma of adult human donors who
have been immunized with tetanus
toxoid, which is used for the
management of tetanus-prone wounds.
Indications: Passive immunization against
tetanus in susceptible people sustaining
serious injury, punctures, cuts, animal
bites and dirty wounds in unimmunized
individuals; treatment of tetanus.
Contraindications: Hypersensitivity to human
immunoglobulins or any component of
the formulation (e.g., thimerosal);
selective IgA deficiencies.
Dose:
Management of tetanus-prone wounds, by IM
injection, ADULT and CHILD > 7 years
old, 250 IU; CHILD < 7 years old, 4 IU/kg,
some recommend 250 IU to small
children.
Treatment of tetanus infection, by IM injection,
ADULT and CHILD, 500 – 6,000 IU,
infiltration of part of the dose around the
wound is recommended.
Tetanus Prophylaxis in Wound Management
W/ CLEAN, ALL OTHER
NO. OF MINOR WOUND WOUNDS
PRIOR Tetanus TIG Tetanus TIG
TETANUS Toxoid Toxoid
TOXOID
DOSES
Yes No Yes Yes
doses

TETANUS 3 or more No. No No. No

Rx IMMUNOGLOBULIN doses

(HUMAN)
Dose Adjustments: No information found.
Inj.: 1,000 IU/mL, 1.5 mL vial (IM) Precautions:
1,500 IU/mL, 1 mL ampul (IM) In those patients with coagulation disorders or
250 IU/mL, 1 mL, 2 mL and 4 mL ampul thrombocytopenia; should not be used
(IM) for IV administration (because of the

Page | 211
ANTI-INFECTIVES
potential for anaphylactic reactions);
drug products made from human plasma
may contain infectious agents, such as
viruses, which can cause diseases.
Pregnancy and lactation (safety has not yet
been established).
TETANUS VACCINE. If schedule requires
tetanus vaccine and antitetanus
immunoglobulin to be administered at
the same time, they should be
administered using separate syringes
and separate sites.
Adverse Drug Reactions:
Common: Erythema, injection site swelling and
pain.
Less Common: Drowsiness, low grade fever,
malaise, mild pyrexia, urticaria.
Rare: Anaphylaxis, angioedema, convulsions,
headache, hives, nausea, vomiting.
Drug Interaction:
Monitor closely with:
Live, attenuated virus vaccines (e.g., measles
and poliomyelitis) and immunoglobulins
– these can influence the ability of
vaccines to induce an immune response
(reduce the efficacy of live vaccines).
Administration: It should be brought to room
temperature before use, and given
slowly by deep IM injection using an
appropriate sized needle; if a large dose
(more than 5 mL) is required, it is
advisable to give it in divided doses at
different sites; the patient should be
observed for at least 20 minutes after
administration.
Administer in the anterolateral aspect of
the upper thigh or the deltoid muscle of
the upper arm. Avoid gluteal region due
to risk of injury to the sciatic nerve. If the
gluteal region has to be used, administer
only in the upper outer quadrant.
TETANUS VACCINE. If schedule requires
tetanus vaccine and antitetanus
immunoglobulin to be administered at
the same time, they should be
administered using separate syringes
and separate sites
Page | 212
STORAGE: Vaccines should be stored within
the safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
VACCINES
BCG VACCINE
Rx
Inj.: Freeze-dried powder, 100
microgram/0.1 mL, 1 mL, 1.5 mL and
2 mL vial (ID)
500 microgram/mL vial + 1 mL diluent
in ampul (ID), 20 doses
A vaccine prepared from bacillus Calmette-
Guerin, an attenuated strain of
Mycobacterium bovis, which reduces the
incidence of meningeal and miliary TB in
early childhood.
Indication: Active immunization against TB.
Contraindications: Known hypersensitivity to
the vaccine or any of its components;
previous TB infection, or tuberculin
reactions >5 mm; HIV infection;
significant fever (give at least 1 month
after fever subsides); patients receiving
immunosuppressive therapy; primary
and secondary immune deficiency
states; generalized septic skin
conditions; burns; pregnancy.
Dose:
NOTE: Tuberculin test must be done before
vaccination (except in infants <6
months); give vaccine if induration is <5
mm 48-72 hours after dose of 10
tuberculin units.
Response to tuberculin test may be
suppressed, if given within 4-6 weeks
following vaccination with live viral
vaccines (e.g., measles, MMR, polio);
ANTI-INFECTIVES
suppressed, in patients receiving
systemic corticosteroids (e.g.
hydrocortisone) or aminocaproic acid;
altered, in malnutrition, age and
presence of disseminated TB.
Immunization against tuberculosis, by ID
injection, ADULT and CHILD >12
months, 0.1 mL; INFANT up to 12
months, 0.05 mL
NOTE: Vaccine is preferably given at birth, or
any time after birth; may be given at the
same time as other live vaccines, if not
given simultaneously, should be given 4
weeks apart; when given to infants, no
need to delay primary immunizations.
Dose Adjustments: No information found.
Precautions:
Pregnancy (first trimester: theoretical risk of
congenital malformations; but the need
for vaccination may, sometimes,
outweigh the possible risk to fetus)
Eczema and scabies (vaccine site should be
lesion-free)
Patients who are known to be at high risk for
HIV infection.
Adverse Drug Reactions:
Common: Enlargement of regional lymph
nodes, ulcer at injection site (2-6 weeks
after vaccination).
Less Common: Fainting, fever, injection site
reactions (pain, redness, itching, small
hard lump that may persist for some
weeks).
Rare: Abscess, allergic reactions including
anaphylaxis, disseminated infection,
keloid formation, lymphadenitis, osteitis.
Drug Interactions:
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
vaccine on the same day or not < 4
weeks apart from another live vaccine).
Avoid concomitant use with:
Anti-infectives – avoid giving live vaccines with
anti-infectives, especially if they are
active against the organism in the
vaccines, as the effectiveness of
vaccines may be reduced, preventing an
immune response.
Immunosuppressive agents (e.g., therapeutic
doses of corticosteroids or
antineoplastics) and during radiation
therapy – may decrease antibody
response to inactivated vaccines.
Administration: Give by ID injection (stretch
skin between thumb and finger) above
the insertion of the deltoid muscle onto
the humerus.
RECONSTITUTION AND ADMINISTRATION.
According to manufacturer’s directions.
STORAGE Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
DIPTHERIA-TETANUS
Rx TOXOIDS AND PERTUSSIS
Inj.: 0.5 mL ampul (IM)
0.5 mL pre-filled syringe (IM)
0.5 mL, 5 mL, 7.5 mL and 10 mL vial (IM)
A three-component preparation of diphtheria,
tetanus and pertussis (whole-cell)
vaccines whose rates of local and
systemic reactions are higher than
acellular pertussis vaccine.
Indication: Active immunization against
diphtheria, tetanus, and pertussis.
Contraindications: Prior systemic
hypersensitivity reaction to the
preparation or any ingredient in the
formulation (e.g., thimerosal); if there
Page | 213
ANTI-INFECTIVES
has been a severe acute neurological
illness within 7 days of pertussis
vaccination; individuals with
thrombocytopenia or any coagulation
disorders.
Dose:
Primary immunization against diphtheria,
tetanus, and pertussis, by IM injection,
ADULT, 0.5 mL; CHILD 1-6 years of age,
two 0.5 mL doses separated by an
interval of 2 months, followed by a third
dose after 6-12 months; INFANT from 6
weeks of age, three 0.5 mL doses with
an interval of at least 4 weeks between
doses.
Dose Adjustments: No information found.
Precautions:
Whole cell pertussis component associated
with more frequent minor adverse
effects than acellular pertussis
component.
Frequency of adverse effects increases with
age and number of injections (vaccines
which contain whole cell pertussis are
not recommended for adolescents and
adults); children with proven, or
suspected, underlying active or
progressive neurologic disorders; defer
vaccination if there was a seizure in the
previous 3 weeks.
Pregnancy (adult vaccine may be used if
necessary).
Arthus-type hypersensitivity: syncope (this has
been reported with use).
Acute illness; bleeding disorders; neurologic
disorders including Guillain Barre
Syndrome; thrombocytopenia; immuno-
deficiency
Adverse Drug Reactions:
Common: Crying, drowsiness, irritability, limb
swelling, restlessness.
Less Common: Fever, lethargy, malaise,
myalgia, transient injection site
reactions (pain, redness, itching,
burning, small hard lump that may
persist for some weeks).
Rare: Allergic reactions including anaphylaxis,
collapse, encephalopathy, headache,
Page | 214
hypotonic-hyporesponsive episodes,
peripheral neuropathy, seizure, urticaria.
NOTE: Immediate treatment for anaphylaxis or
hypersensitivity reactions, including
epinephrine 1:1000 should be available
during administration of the vaccine
Drug Interactions:
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
vaccine on the same day or not < 4
weeks apart from another live vaccine).
Avoid concomitant use with:
Immunosuppressive agents (e.g., therapeutic
doses of corticosteroids or
antineoplastics) and during radiation
therapy – these may decrease antibody
response to inactivated vaccines.
NOTE: Any agent which is active against the
bacterial or viral strain present in the
vaccine may interfere with the
development of a protective immune
response, but treatment with
antibacterials is not a contraindication to
immunization.
Administration:
For IM administration only into the
anterolateral aspect of the thigh of the
deltoid muscle. Do not give IV or SC.
Live vaccines should either be given
simultaneously (at different sites) or at
an interval of at least three weeks. Live
vaccines should normally be given at
least three weeks before, or at least
three months after the use of
immunoglobulin.
NOTE: Travellers should receive appropriate
vaccines regardless of the limitations if
time is short.
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
ANTI-INFECTIVES
Precautions:
HAEMOPHILUS INFLUENZA Anaphylactoid or hypersensitivity reactions
Rx TYPE B CONJUGATED (immediate treatment, including
epinephrine 1:1000 should be available
VACCINE (HIB) during vaccine use);
Syncope (has been reported with use);
Acute illness;
Inj.: 10 micrograms/0.5 mL, 1 dose vial + 0.5 Bleeding disorders (bleeding or hematoma
mL diluent with tetanus protein (IM) may occur from IM administration);
10 micrograms/0.5 mL vial + 0.9% Guillain-Barré syndrome;
sodium chloride with diphtheria CRM Immunodeficiency;
197 protein (IM) Children (apnea has occurred following
0.5 mL vial with meningococcal protein vaccination in premature infants);
(IM) Pregnancy (animal reproduction studies have
not been conducted).
An inactivated bacterial vaccine that
stimulates the production of anticapsular Adverse Drug Reactions:
antibodies and provides active immunity Common: Crying (unusual, high-pitched,
to Haemophilus influenzae type b. prolonged), drowsiness, fussiness,
irritability, lethargy, pain, restlessness,
Indications: Active immunization for the seizure, skin rash, urticaria, anorexia,
prevention of invasive disease caused by diarrhea, vomiting, thrombocytopenia,
Haemophilus influenzae type b (Hib) erythema, induration, pain, soreness,
swelling, weakness, otitis media,
Contraindications: Hypersensitivity to tracheitis, upper respiratory tract
Haemophilus b polysaccharide or any infection, fever
component of the formulation
Less Common: Abscess at injection site
Dose: (sterile), anaphylaxis, anaphylactoid
Immunization, by IM injection, ADULT, 0.5 mL reaction, apnea, angioedema, febrile
[NOTE: For adult recipients of successful seizures, Guillain-Barré syndrome,
hematopoietic stem cell transplant, hypersensitivity reaction, hypotonic /
revaccinate with a 3-dose regimen hyporesponsive episode,
beginning 6–12 months after transplant, lymphadenopathy, malaise, mass,
regardless of vaccination history; peripheral edema, pneumonia, pruritus,
administer ≥4 weeks apart]. swelling of the injected limb (extensive),
syncope, vasodepressor syncope
Primary immunization, by IM injection, CHILD,
0.5 Drug Interactions:
mL per dose; number of doses for Avoid concomitant use with:
completion of Hib series depends on Drugs that reduce therapeutic effect of Hib
products, including some combination Vaccine:
formulations, see specific product Belimumab
monographs for specific dosing Fingolimod [administer at least 2 weeks
information. apart; if vaccinated during fingolimod
therapy, revaccinate 2–3 months after
Booster immunization, by IM injection, CHILD fingolimod discontinuation]
≥12 Immunosuppressants [Cytarabine,
months, 0.5 mL as a single dose. Liposomal] [administer at least 2 weeks
Page | 215
ANTI-INFECTIVES
apart; if vaccinated during
immunosuppressant therapy,
revaccinate at least 3 months after
immunosuppressant discontinuation]
TEST INTERACTION. May interfere with urine
antigen detection test; antigenuria may
occur up to 2 weeks following
immunization.
Administration: For IM administration into the
anterolateral thigh or deltoid muscle. Do
NOT administer into buttocks due to
potential risk of injury to sciatic nerve. Do
NOT inject by IV, ID, or SC.
Shake well prior to use. Do NOT mix with
other vaccines or injections. Use
different needles and syringes for each
injection.
Administer while seated or lying down to
prevent syncope related injuries.
Pregnancy Category: C
HEPATITIS B VACCINE
Rx (RECOMBINANT DNA)
Inj.: 10 micrograms/0.5 mL monodose vial
(IM) (pediatric)
10 micrograms/0.5 mL, 5 mL vial (10
dose) vial (IM)
20 micrograms/mL monodose vial
(IM) (adult) (For more than 10 years
old)
20 micrograms/mL, 10 mL vial (10
doses per vial), adult
N.B.: Formulations of different manufacturers
are of equal or similar immunogenicity.
Follow the re-commended dose of each
manufacturer strictly
A non-infectious subunit viral vaccine, which
confers active immunity via formation of
anti-hepatitis B antibodies. The vaccine
Page | 216
is derived from hepatitis B surface
antigen (HBsAg) produced through
recombinant DNA techniques from yeast
cells.
Indication: Active immunization against
infection caused by all known subtypes
of hepatitis B virus (HBV)
Contraindications: Severe allergic or
hypersensitivity reaction to yeast,
hepatitis B vaccine, or any component of
the formulation
Dose: Primary immunization, by IM injection,
ADULT, three 1 mL doses at 0, 1, and 6
months; ADOLESCENT, CHILD, and
INFANT, three 0.5 mL doses at 0, 1, and
6 months.
Dose Adjustment:
Renal Impairment: For adult pre-dialysis and
dialysis patients ≥20 years, administer
40 micrograms per dose at 0, 1, and 6
months.
Precautions:
Anaphylactoid or hypersensitivity reactions
(immediate treatment, including
epinephrine 1:1000 should be available
during vaccine use);
Syncope (has been reported with use); Acute
illness; Bleeding disorders, including
thrombocytopenia; Multiple sclerosis;
Immunodeficiency; Severely
compromised cardiopulmonary status;
Pregnancy (animal reproduction studies have
not been conducted); Lactation (not
known if excreted into breastmilk).
Adverse Drug Reactions:
Common: Flushing, hypotension, body pain,
chills, dizziness, drowsiness, fatigue,
headache, insomnia, irritability, malaise,
paresthesia, tingling sensation, vertigo,
diaphoresis, pruritus, skin rash,
urticaria, abdominal pain, anorexia,
decreased appetite, diarrhea,
dyspepsia, nausea, stomach cramps,
vomiting, dysuria, lymphadenopathy,
angioedema, influenza, injection site
reactions (bruising, erythema,
ANTI-INFECTIVES
induration, nodule, itching, soreness,
pain, swelling, tenderness, warmth),
arthralgia, back pain, myalgia, neck pain,
neck stiffness, shoulder pain, weakness,
otalgia, cough, pharyngitis, rhinitis,
upper respiratory tract infection, fever
Less Common: Acute exacerbations of multiple
sclerosis, agitation, alopecia,
anaphylactoid reaction, anaphylaxis,
apnea, arthritis, Bell's palsy,
bronchospasm, constipation, eczema,
conjunctivitis, encephalitis, erythema
nodosum, erythema multiforme, febrile
seizures, Guillain-Barré syndrome,
herpes zoster, hypersensitivity reaction,
hypoesthesia, increased erythrocyte
sedimentation rate, keratitis, lichen
planus, limb pain, lupus-like syndrome,
meningitis, migraine, multiple sclerosis,
myasthenia, myelitis, neuritis,
neuropathy, optic neuritis, palpitations,
paralysis, paresis, periarteritis nodosa,
peripheral neuropathy, petechia,
purpura, radiculopathy, seizure, serum
sickness-like reaction, Stevens-Johnson
syndrome, syncope, systemic lupus
erythematosus, tachycardia,
thrombocytopenia, tinnitus, transverse
myelitis, uveitis, vasculitis, visual
disturbance
Drug Interactions:
Avoid concomitant use with:
Drugs that reduce therapeutic effect of HBV
vaccine: Immunosuppressants
[Cytarabine, Liposomal] [administer at
least 2 weeks apart; if vaccinated during
immuno- suppressant therapy,
revaccinate at least 3 months after
immunosuppressant discontinuation]
Administration:
For IM administration into the deltoid muscle
for adults or into the anterolateral aspect
of the thigh in infants and young
children. Do not administer to the gluteal
region.
Do not administer by IV, ID, or SC.
Shake well prior to withdrawal and use. Do not
mix with other vaccines or injections. Use
different needles and syringes for each
injection.
Administer while patient is seated or lying
down to prevent syncope related
injuries.
NOTE: For patients at risk of hemorrhage
following IM injection, administer by IM
only if, in the opinion of the physician
familiar with the patient's bleeding risk,
the vaccine can be administered by this
route with reasonable safety. Use a fine
needle (23 gauge or smaller) and apply
firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or other
similar therapy, intramuscular
vaccination can be scheduled shortly
after such therapy is administered.
Patients on anticoagulant therapy
should be considered to have the same
bleeding risks and treated as those with
clotting
Pregnancy Category: C
INFLUENZA POLYVALENT
Rx VACCINE
Inj.: 0.5 mL vial + pre-filled syringe diluent
(IM)
0.5 mL suspension in a pre-filled syringe
or ampul (IM) (adult)
15 micrograms/0.5 mL, 5 mL multidose
glass vial
N.B.: Strains as recommended by WHO
A sterile, aqueous suspension of suitable
strains of influenza virus types A and B,
which are developed separately in
embryonated hen eggs and inactivated.
This promotes immunity to seasonal
influenza virus by inducing specific
antibody production.
Indication: Active immunization against
influenza in individuals at risk.
Contraindications: Severe allergies including
anaphylactic reactions to previous doses
Page | 217
ANTI-INFECTIVES
of influenza vaccine, chicken or egg
protein, or any component of the
formulation; acute, severe febrile illness.
Dose:
Immunization, by IM injection, (annually for
high-risk persons), ADULT,
ADOLESCENT, and CHILD ≥9 years, 0.5
mL/dose as a single dose per season;
CHILD 6 months to 8 years, one or two
0.5 mL doses per season
(NOTE: For infants and children 6
months to
< 9 years old, the 2 doses need not have
been received during the same season
or consecutive seasons).
Dose Adjustments: No information found.
Precautions:
Anaphylaxis reactions to eggs (may be able to
receive influenza vaccine if egg
ovalbumin <1 microgram/dose; seek
the advice of a specialist);
Children (adverse effects, such as fever,
myalgia and malaise, may be more
severe in children <5 years than in older
children and adults);
Oculorespiratory syndrome; syncope (has been
reported with use); Acute illness;
Bleeding disorders, including
thrombocytopenia; Febrile seizures;
Guillain-Barré Syndrome; HIV infection;
Neurologic disorders;
Immunodeficiency;
Elderly (antibody responses may be lower and
decline faster);
Pregnancy (has not shown to cause fetal harm
when given to pregnant women);
breastfeeding (not known to be harmful).
Adverse Drug Reactions:
Common: Fever, headache, malaise, myalgia,
chills, chest tightness, fatigue,
diaphoresis, arthralgia, back pain,
anorexia, nausea.
Less Common: Fainting, transient injection site
reactions (pain, redness, itching,
burning, small hard lump that may
persist for some weeks), dizziness,
syncope, urticaria, weakness.
Page | 218
Rare: Allergic reactions, including asthma,
hives, angioedema, anaphylaxis;
Guillain-Barré syndrome.
NOTE: Immediate treatment for
anaphylaxis should be available,
(including epinephrine, 1:1000).
Drug Interactions:
NOTE: Monitoring for possible enhanced drug
effect or toxicity should be considered
for persons taking medications
metabolized by the cytochrome P450
system, including warfarin, theophylline
or anticonvulsant when they receive
influenza virus vaccination.
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
vaccine on the same day or not < 4
weeks apart from another live vaccine).
Phenytoin – enhanced effect of phenytoin.
Warfarin – occasionally enhanced effect of
warfarin.
Avoid concomitant use with:
Immunosuppressive agents (e.g., therapeutic
doses of corticosteroids or
antineoplastics) and during radiation
therapy – these may decrease antibody
response to inactivated vaccines.
NOTE: Any agent which is active against the
bacterial or viral strain present in the
vaccine may interfere with the
development of a protective immune
response, but treatment with
antibacterials is not a contraindication to
immunization.
Administration:
For IM administration into the deltoid muscle
for adults and older children, or into the
anterolateral aspect of the thigh for
infants and young children. Children ≥1
year with adequate deltoid muscle mass
may be vaccinated in the deltoid.
Do NOT inject into the gluteal region or
areas where there may be a major nerve
trunk.
ANTI-INFECTIVES
Shake well prior to use. Visually inspect
for particulate matter and discoloration
prior to administration.
NOTE: For patients at risk of hemorrhage
following IM injection, administer by IM
only if, in the opinion of the physician
familiar with the patient's bleeding risk,
the vaccine can be administered by this
route with reasonable safety. Use a fine
needle (23 gauge or smaller) and apply
firm pressure to the site (without
rubbing) for at least 2 minutes.
If the patient receives anti-hemophilia or
other similar therapy, intramuscular
vaccination can be scheduled shortly
after such therapy is administered.
Patients on anticoagulant therapy
should be considered to have the same
bleeding risks and treated as those with
clotting factor disorders. Pregnancy
Category: C ATC Code: J07BB01
(inactivated) J07BB03 (live attenuated)
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
MEASLES VACCINE (LIVE
Rx ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
Multidose vial + 5 mL diluent (SC)
A live, attenuated, single-antigen vaccine
prepared through chick embryo tissue
culture.
Indication: Active immunization against
measles.
Contraindications:
Hypersensitivity to any component of the
formulation; severe immunodeficiency;
febrile states; acute infectious diseases;
leukemia; severe anemia; other severe
blood disorders; severe renal
impairment; decompensated heart
diseases; pregnancy.
Dose: Immunization, by SC injection, ADULT
and CHILD, single 0.5 mL dose.
Dose Adjustments: No information found.
Precautions:
Children with a history of hypersensitivity
(anaphylaxis) to egg protein must receive
the vaccine in a setting where reactions
can be managed; tuberculin and other
skin test reactions may be temporarily
reduced; children with history of seizures
should be immunized after advising the
parents that the risk of seizure after
immunization is slightly increased (may
require treatment in reducing fever 5-12
days after giving the vaccine).
Pregnancy (first trimester: risk of congenital
malformations, but need for vaccination
may, sometimes, outweigh possible risk
to fetus; avoid MMR); thrombocytopenia.
Adverse Drug Reactions:
NOTE: Adverse reactions are considerably less
common after the second dose.
Common: Arthralgia and arthritis (in women),
fever, headache, lymphadenopathy,
rash, sore throat.
Less Common: Arthralgia and arthritis (in
children), fainting, febrile seizures,
parotid swelling, transient injection site
reactions (pain, redness, itching,
swelling/burning, small hard lump that
may persist for some weeks).
Rare: Allergic reactions including anaphylaxis,
meningitis, chronic joint symptoms,
encephalitis, purpura,
thrombocytopenia.
NOTE: Immediate treatment for
anaphylaxis should be available,
(including epinephrine, 1:1000).
Drug Interactions:
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
Page | 219
ANTI-INFECTIVES
vaccine on the same day or not < 4
weeks apart from another live vaccine).
Avoid concomitant use with:
Immunosuppressive agents (e.g., therapeutic
doses of corticosteroids or
antineoplastics) and during radiation
therapy – these may decrease antibody
response to inactivated vaccines.
NOTE: Any agent which is active against the
bacterial or viral strain present in the
vaccine may interfere with the
development of a protective immune
response, but treatment with
antibacterials is not a contraindication to
immunization.
Administration: For deep SC injection into the
anterolateral aspect of the upper thigh in
toddlers and deltoid muscle in older
children.
Administered subcutaneously,
preferably into the outer aspect of the
upper arm (special care should be taken
to ensure that the injection does not
enter a blood vessel).
Reconstitute only with the supplied diluent
using a sterile syringe and needle. Use
reconstituted vaccine immediately. If
reconstituted vaccine is not used
immediately, store in the dark at 2–8oC
for no longer than 6 hours. Discard all
opened containers after 6 hours.
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
See Measles, Mumps, and Rubella (MMR)
Vaccine (Live Attenuated) under
Vaccines – Viral Vaccines in Chapter 7:
Antiinfectives for Systemic Use for other
information.
Page | 220
MEASLES MUMPS AND
Rx RUBELLA (MMR)
VACCINE (LIVE
ATTENUATED)
Inj.: Monodose vial + 0.5 mL diluent (SC)
Multidose vial + 5 mL diluent (SC)
A bacterially sterile, freeze-dried preparation of
live, attenuated strains of measles,
mumps and rubella virus that may
contain antimicrobial agents.
Indications: Active immunization for
simultaneous vaccination against
measles, mumps, and rubella in patients
≥12 months of age
Contraindications: Hypersensitivity to measles,
mumps, and/or rubella vaccine or any
component of the formulation (including
neomycin); current febrile respiratory
illness or other febrile infection; primary
and acquired immunodeficiency states;
patients on immunosuppressive
therapy; blood dyscrasias, leukemia,
lymphomas, or other malignant
neoplasms affecting the bone marrow or
lymphatic systems; family history of
congenital or hereditary
immunodeficiency; pregnancy.
Dose:
NOTE: The minimum interval between 2 doses
is 28 days.
Immunization, by SC injection, ADULT, one or
two 0.5 mL doses administered at least
28 days apart; CHILD ≥12 months, two
0.5 mL doses, first dose is
recommended at 12–15 months of age;
second dose is recommended at 4–6
years of age, prior to entering
kindergarten or first grade; second dose
may be administered at any time
provided 28 days have elapsed.
Dose Adjustments: No information found.
Precautions:
ANTI-INFECTIVES
Anaphylactoid or hypersensitivity reactions,
Syncope (has been reported with use);
Acute illness; CNS disorders; Measles,
Mumps and Rubella exposure;
Thrombocytopenia; Tuberculosis - oculomotor nerve paralysis, optic
untreated TB (MMR can exacerbate the
condition; vaccinate when TB is being
treated); Immunodeficiencies; Elderly
(antibody responses may be lower and
decline faster); Children (safety and
efficacy of measles vaccine have not
been established in children < 12
months of age)
Children with history of seizures (may require
treatment to reduce fever 5-12 days
after vaccination); untreated TB (MMR
can exacerbate the condition; vaccinate
when TB is being treated); treatment
with immunoglobulins, whole blood
(normal immunoglobulin may interfere
with the immune response to some live
virus vaccines; do not administer MMR
vaccine for 3 months after IM
immunoglobulin or whole blood, or 9
months after IV immunoglobulin).
Pregnancy: avoid pregnancy for 28 days after
vaccination; non-immune pregnant
women should be vaccinated
postpartum.
Adverse Drug Reactions:
NOTE: Adverse reactions are considerably less
common after second dose.
Common: Fever, headache, lymphadenopathy,
rash, sore throat; arthralgia (arthritis in
women);
Others: syncope, vasculitis, acute
disseminated encephalomyelitis, ataxia,
dizziness, brain disease, encephalitis,
Guillain-Barré syndrome, irritability,
malaise, measles inclusion body
encephalitis, paresthesia,
polyneuropathy, retrobulbar neuritis,
seizure, subacute sclerosing
panencephalitis, transverse myelitis,
erythema multiforme, pruritus, Stevens-
Johnson syndrome, urticaria, diabetes
mellitus, nausea, diarrhea, pancreatitis,
parotitis, vomiting, epididymitis,
leukocytosis, orchitis, purpura,
anaphylactoid reaction,
thrombocytopenia, anaphylaxis,
angioedema, injection site reactions
(burning, induration, redness, stinging,
swelling, tenderness, vesiculation,
wheal, flare), myalgia, conjunctivitis,
neuritis, optic papillitis, retinitis, nerve
deafness, otitis media, bronchospasm,
cough, pneumonia, pneumonitis,
rhinitis, atypical measles, febrile
seizures, panniculitis,
Less Common: Arthralgia and arthritis (in
children), fainting, febrile seizures,
parotid swelling, transient injection site
reactions (pain, redness, itching,
swelling, burning, small hard lump that
may persist for some weeks).
Rare: Allergic reactions including anaphylaxis,
meningitis, chronic joint symptoms,
encephalitis, purpura,
thrombocytopenia.
NOTE: immediate treatment, including
epinephrine 1:1000 should be available
during vaccine use.
Drug Interactions:
Avoid concomitant use with:
Drugs that Increase risk of adverse or toxic
effects of MMR Vaccine: Azathioprine
Corticosteroids (Systemic) Dimethyl
Fumarate (vaccinal infection)
Immunosuppressants Mercaptopurine
Methotrexate
Drugs that Reduces therapeutic effect of MMR
Vaccine: Azathioprine [avoid doses >3
mg/kg daily], Corticosteroids (Systemic)
[avoid doses greater than an equivalent
of 2 mg/kg or 20 mg/day of prednisone
for ≥2 weeks], Dimethyl Fumarate,
Immune Globulins [consult full
interaction monograph for dose interval
recommendations],
Immunosuppressants [except
Azathioprine; Beclomethasone (Oral
Inhalation); Betamethasone (Systemic);
Budesonide (Systemic); Budesonide
(Systemic and Oral Inhalation);
Corticotropin; Cortisone; Cytarabine
(Liposomal); , Dexamethasone
(Systemic); Fludrocortisone; Fluticasone
(Oral Inhalation); Hydrocortisone
(Systemic); , Mercaptopurine;
Methotrexate; Methylpred- nisolone;
Page | 221
ANTI-INFECTIVES
Prednisolone (Systemic); Prednisone;
Triamcinolone, (Systemic) [separate
administration by at least 3 months],
Mercaptopurine [avoid doses >1.5
mg/kg daily] Methotrexate [avoid doses
>0.4 mg/kg weekly]
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
vaccine on the same day or not <4
weeks apart from another live vaccine).
NOTE: Any agent which is active against the
bacterial or viral strain present in the
vaccine may interfere with the
development of a protective immune
response, but treatment with
antibacterials is not a contraindication to
immunization.
TEST INTERACTION. Temporarily suppresses
tuberculin skin test reactivity. [Separate
administration by at least 4–6 weeks]
Administration:
For SC administration into the outer aspect of
the upper arm in patients ≥12 months.
Do not inject by IV.
Reconstitute vaccine using the provided
diluent. Gently agitate to mix thoroughly.
Discard if powder does not dissolve. Use
immediately after reconstitution. Do not
mix with other vaccines or injections. Use
different needles and syringes for each
injection.
Administer while patient is seated or lying
down to prevent syncope related
injuries.
Store the powder at 2–8°C prior to
reconstitution. Protect from light. Store
diluent in refrigerator or at room
temperature. Do not freeze diluent.
Store the lyophilized vaccine between 2
to 8˚C to maintain potency. May be
stored under refrigeration for up to 8
hours. Discard unused portions after 8
hours.
Page | 222
Administration: Administered subcutaneously,
preferably into the outer aspect of the
upper arm (special care should be taken
to ensure that the injection does not
enter a blood vessel).
NOTE: Vaccines should be stored within the
safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
MENINGOCOCCAL
Rx (Neisseria meningitides)
POLYSACCHARIDE VACCINE
Inj.: 50 micrograms/0.5 mL dose (Group A + C)
lyophilized powder, single dose + 0.5 mL
diluent syringe (IM, SC)
50 micrograms/0.5 mL dose (Group A + C)
lyophilized powder, multi-dose (10
doses) + 5 mL diluent vial (IM, SC)
50 micrograms/0.5 mL dose (Serogroup A
+ Serogroup B + Serogroup W135 +
Serogroup Y) lyophilized powder, multi-
dose (10 doses) + diluent vial (IM, SC)
An inactivated bacterial vaccine that induces
the formation of bactericidal antibodies
to meningococcal antigens. The
presence of these antibodies is strongly
correlated with immunity to
meningococcal disease caused by
Neisseria meningitidis.
Indication: Active immunization of patients 2
years and older to prevent invasive
meningococcal disease caused by
Neisseria meningitidis
Contraindication: Hypersensitivity to any
component of the formulation
ANTI-INFECTIVES
Dose:
Immunization, by SC injection, ADULT, Administration:
ADOLESCENT, and CHILD ≥ 2 years, 0.5 Administer by SC injection into the deltoid
mL per dose. region.
Precautions: Do NOT administer by ID, IM, or IV.
Anaphylactoid or hypersensitivity reactions
Syncope (has been reported with use); Administer while seated or lying down to
Acute illness; prevent syncope related injuries.
Meningococcal infections (not to be used to
treat Reconstitute using provided diluent. Shake
meningococcal infections); well.
Immunodeficiency;
Elderly (no specific data available; Store at 2–8oC. Do NOT freeze. Use single-
recommended dose vial immediately after
only when traveling to highly endemic reconstitution. Use multidose vial
areas); within 35 days of reconstitution. Do
Pregnancy (animal reproduction studies have NOT mix with other vaccines or
not injections. Use different needles and
been conducted); syringes for each injection.
Lactation (not known if excreted in breastmilk).
Pregnancy Category: C
Adverse Drug Reactions:
Common: Headache, fatigue, malaise,
drowsiness, irritability, chills, fever,
rash, diarrhea, anorexia, vomiting, POLIOMYELITIS VACCINE
injection site reactions (pain, redness, Rx (TYPES 1, 2 and 3)
induration, swelling), arthralgia
Less Common: Dizziness, Guillain-Barré [INACTIVATED]
syndrome, hypersensitivity
(angioedema, dyspnea, pruritus, rash, Inj.: 0.5 mL per dose suspension for
urticaria), anaphylaxis, myalgia, injection, single dose / multi-dose vial
nausea, paresthesia, vasovagal (IM, SC)
syncope, weakness
NOTE: immediate treatment of An inactivated viral vaccine that induces active
anaphylaxis or severe hypersensitivity immunity against poliovirus types 1, 2, and
reactions, including epinephrine 3 infection.
1:1000 should be available during
vaccine use. Indications: Active immunization against
poliomyelitis caused by poliovirus type 1, 2,
Drug Interactions: and 3.
Avoid concomitant use with:
Drugs that reduce therapeutic effect of Contraindications: Hypersensitivity to any
MeningococcalVaccine: component of the vaccine
Immunosuppressants [Cytarabine,
Liposomal] [administer at least 2 Dose:
weeks apart; if vaccinated during Immunization, by IM or SC injection, ADULT
immune- suppressant therapy, (previously unvaccinated), three 0.5 mL
revaccinate at least 3 months after doses, administer 2 doses at 1–2 month
immunosuppressant discontinuation] intervals and the third dose 6–12 months

Page | 223
ANTI-INFECTIVES
later; ADULT (incompletely vaccinated), for
adults with <3 doses of OPV and/or IPV,
administer at least one 0.5 mL dose; ADULT
(completely vaccinated by at increased risk
of exposure), one 0.5 mL dose.
Primary immunization, by IM or SC injection,
CHILD and INFANT 6 weeks to 47 months,
three 0.5 mL doses at 2, 4, and 6–18
months of age.
Booster immunization, by IM or SC injection,
CHILD 4 to 6 years, 0.5 mL as a single dose
at least 6 months after last dose;
administer final booster dose at ≥4 years of
age, regardless of number of previous
doses.
Precautions:
Anaphylactoid or hypersensitivity reactions
(immediate treatment, including
epinephrine 1:1000 should be available
during vaccine use); syncope (has been
reported with use); acute illness;
immunodeficiency.
Elderly (boosters may be necessary since
antibody titers may diminish with age).
Pregnancy (animal reproduction studies have
not been conducted).
Adverse Drug Reactions:
Common: Irritability, tiredness, fever, anorexia,
vomiting, injection site reactions
(tenderness, swelling, erythema), persistent
crying
Less Common: Agitation, anaphylactic shock,
allergic reaction, anaphylaxis,
hypersensitivity reactions, arthralgia, febrile
seizures, lymphadenopathy, headache,
myalgia, paresthesia, rash, seizures,
somnolence, urticaria
NOTE: immediate treatment, including
epinephrine 1:1000 should be available
during vaccine use.
Rare: Guillain-Barré syndrome
Immunosuppressants [Cytarabine,
Liposomal] [administer at least 2 weeks
apart; if vaccinated during
immunosuppressant therapy, revaccinate
at least 3 months after
immunosuppressant discontinuation]
TEST INTERACTION. May temporarily suppress
tuberculin skin test sensitivity (4–6 weeks).
Administration:
For IM or SC administration into the midlateral
aspect of the thigh in infants and small
children or in the deltoid area in adults or
older children.
Administer while patient is seated or lying
down to prevent syncope related injuries.
NOTE: For patients at risk of hemorrhage
following IM injection, administer by IM only
if, in the opinion of the physician familiar
with the patient's bleeding risk, the vaccine
can be administered by this route with
reasonable safety. Use a fine needle (23
gauge or smaller) and apply firm pressure to
the site (without rubbing) for at least 2
minutes.
If the patient receives anti-hemophilia or
other similar therapy, intramuscular
vaccination can be scheduled shortly after
such therapy is administered. Patients on
anticoagulant therapy should be considered
to have the same bleeding risks and treated
as those with clotting factor disorders.
Pregnancy Category: C

Drug Interactions:
Avoid concomitant use with:
Drugs that reduce therapeutic effect of
Influenza Vaccine:

Page | 224
ANTI-INFECTIVES
LIVE ATTENUATED
Rx BIVALENT ORAL POLIO
VACCINE (TYPE 1 AND 3)
Inj: 2 mg vial (20 doses)
Consists of bivalent, live attenuated
poliomyelitis virus vaccine of the Sabin
strains Type 1 and Type 3
Indication: Indicated for active immunization in
all age groups against infection caused
by poliomyelitis viruses of Type 1 and 3.
Contraindications: is contraindicated in those
with known hypersensitivity to neomycin
or polymyxin or any other component of
the vaccine, in subjects having shown
signs of hypersensitivity after previous
administration of oral poliomyelitis
vaccines.
Dose:
Primary vaccination or booster doses should
be given following official
recommendations. Given by oral
administration.
Dose Adjustments:
Renal and Hepatic Impairment:
No information.
Precautions:
Hypersensitivity reactions
Pregnancy
Gastrointestinal infections (e.g., diarrhea and
vomiting)
Fecal excretion of the vaccine viruses may
persist for several weeks and may be
transmitted to the contacts of the
vaccines; contacts of vaccines should be
warned about need for strict personal
hygiene.
Adverse Drug Reactions:
Common: Fever, vomiting, diarrhea.
Rare: Vaccine-associated paralysis.
Drug Interactions:
Can be administered at the same time as the
Haemophilus influenzae type b vaccine,
hepatitis B vaccine, diphtheria, pertussis
and/or tetanus vaccine, measles, rubella
and/or mumps vaccine, yellow fever
vaccine, or BCG vaccine if this fits into the
vaccination schedule.
Immunosuppressive treatment may reduce the
immune response, may favor the
multiplication of the vaccine viruses, and
may increase the length of excretion of
the vaccine viruses in the stools.
Administration:
For oral use only.
Do not inject.
The vaccine dose is two drops (0.1 mL
measured using a multi-dose container).
The vaccinating dose can be administered
directly in the mouth or on a sugar lump.
If a dropper is used, care must be taken not to
contaminate the dropper with the saliva.
Should be administered to breastfed infants,
preferably two hours before or after
breastfeeding, to avoid contact with the
antibodies present in the breast milk.
STORAGE: Store in the freezer (-20 °C). Do not
use after the expiration date printed on
the syringe.
After thawing, the product can be stored for 6
months in the refrigerator (2 °C to 8 °C).
RABIES VACCINE,
Rx CHICK EMBRYO CELL
(PURIFIED, INACTIVATED)
Inj.: lyophilized powder, 2.5 IU/mL, 1 dose
vial + 1 mL diluent (ID, IM)
Purified vaccine containing inactivated rabies
virus cultivated in chick embryo cells.
Page | 225
ANTI-INFECTIVES
Indications: Active immunization against
rabies; pre-exposure and post-exposure
prevention
NOTE: WHO recommends pre-exposure
immunization of individuals at high risk of
contracting rabies, including people living or
traveling to enzootic areas and those at risk
due to occupational exposure, such as
health and laboratory workers, animal
handlers, veterinary surgeons, etc.
Contraindications: Hypersensitivity to the
vaccine or any of its components; fever;
acute illness
Dose:
Pre-exposure vaccination, by IM injection,
ADULT and CHILD, three 0.5 mL doses on
days 0, 7, and 28, followed by one 0.5 mL
booster dose after 1 year and every 5 year
hence after; may administer third dose as
early as day 21 if time is limited;
by ID injection, ADULT and CHILD, three 0.1 mL
doses on days 0, 7, 28, followed by one 0.5
mL booster dose after 1 year and every 5
year hence after; may administer third dose
as early as day 21 if time is limited.
Pre-exposure vaccination, by IM injection,
ADULT and CHILD (fully immunized within
the last 5 years, with a cell culture rabies
vaccine), two 0.5 mL doses on days 0 and
3; ADULT and CHILD (non-immunized,
immunized more than 5 years ago, or
incomplete vaccination), five 0.5 mL doses
on days 0, 3, 7, 14, and 28 with 20 IU/kg of
body weight human rabies
immunoglobulins (RIG) or 40 IU/kg of body
weight equine RIG, administered at the
same time as the first injection for severe
injuries [NOTE: Administer vaccine
contralaterally to the RIG administration
sites];
by ID injection, ADULT and CHILD (fully
immunized within the last 5 years, with a
cell culture rabies vaccine), two 0.1 mL
doses on days 0 and 3; ADULT and CHILD
(non-immunized, immunized more than 5
years ago, or incomplete vaccination), one
Page | 226
0.1 mL dose at 2 sites on days 0, 3, 7, 14,
and 28 with 20 IU/kg of body weight human
rabies immunoglobulins (RIG) or 40 IU/kg of
body weight equine RIG, administered at
the same time as the first injection for
severe injuries [NOTE: Administer vaccine
contralaterally to the RIG administration
sites].
Precautions:
Anaphylactoid or hypersensitivity reactions
(immediate treatment, including
epinephrine 1:1000 should be available
during vaccine use);
Syncope (has been reported with use);
Immunodeficiency;
Elderly (boosters may be necessary since
antibody titers may diminish with age).
Pregnancy (requires dose adjustment).
SKILLED TASKS. May cause post-vaccination
dizziness. Avoid performing tasks, which
require mental alertness, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Common: Injection site reactions (pain,
erythema, edema, pruritus, induration),
fever, shivering, malaise, asthenia,
headache, dizziness, arthralgia, myalgia,
nausea, abdominal pain
Rare: Anaphylactoid reaction, urticaria, rash
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of Rabies Vaccine:
Immunoglobulins
Avoid concomitant use with:
Reduces therapeutic effect of Rabies Vaccine:
Corticosteroids (may cause failure of
vaccination)
Other Immunosuppressants (may cause
failure of vaccination)
Administration: For IM administration into the
deltoid region in adults and children or the
anterolateral thigh for children <2 years of
age. Do NOT inject into the gluteal area
ANTI-INFECTIVES
because weaker levels of neutralizing
antibodies have been observed when this
area is used.
May also administer by ID injection as an
alternative into the upper or forearm. ID
route must be administered only by medical
staff trained in this technique to ensure
vaccine is delivered by ID and NOT by SC.
Use sterile syringe with fixed needle (insulin
type). Do NOT inject by IV or SC.
Thoroughly clean bite wound prior to
administration. Immediately flush out and
wash with soap or detergent to eliminate
rabies virus at the infection site. Thoroughly
remove all traces of soap then apply 70%
alcohol solution, tincture or solution of
iodine, or 0.1% quaternary ammonium
solution.
Reconstitute using the solvent provided. Shake
gently to obtain a homogenous suspension,
appearing as a limpid liquid. Immediately
administer vaccine. Reconstituted vaccine
may be used for up to 8 hours provided it is
maintained at 2–8oC. Discard unused
portions after 8 hours.
Pregnancy Category: C
ATC Code: J07BG01
RABIES VACCINE,
Rx VERO CELL (PURIFIED)
Inj.: lyophilized powder, 2.5 IU/ 0.5 mL, vial +
diluent (ID, IM)
2.5 IU/mL suspension, 1 mL vial (IM)
A vaccine that contains inactivated rabies virus
cultivated in Vero cells.
Indications: Active immunization against
rabies; pre-exposure prophylaxis, and
post-exposure treatment.
NOTE: WHO recommends pre-exposure
immunization of individuals at increased
risk of contracting rabies, including
those at risk due to occupational
exposure (such as health and laboratory
workers, animal handlers, and veterinary
surgeons), and people living or traveling
to enzootic areas (in such areas, children
aged 5-15 years are at particular risk of
exposure).
Contraindications: Known hypersensitivity to
the vaccine or any of its components;
vaccines of nerve cell tissue origin
should not be used (due to being less
potent and are frequently associated
with adverse events);
fever; acute illness.
Dose:
NOTE: The treatment is dependent upon the
individual’s immune status and upon the
level of risk of rabies. Doses may vary
between products.
Pre-exposure prophylaxis against rabies:
By IM injection, ADULT and CHILD, 3
doses of 0.5 mL each, given on days 0,
7, and 28 (day 28 preferable, but
administration may be advanced
towards day 21 if time is limited); or,
By ID injection, 3 doses of 0.1 mL each,
given on days 0, 7, 28 (administration on
day 28 may be advanced towards day 21
if time is limited).
BOOSTER DOSES.
Periodic booster doses are
recommended only for individuals whose
occupation puts them at continuous or
frequent risk of rabies exposure. In such
cases, a booster dose should be given at
intervals dictated by regular testing for
antibodies (a concentration of virus
neutralizing antibodies of at least 0.5
IU/mL indicates protection). Where
serological testing is unavailable,
booster vaccination every 5 years may
be an acceptable alternative.
Post-exposure treatment against rabies in
unimmunized individuals, or those
Page | 227
ANTI-INFECTIVES
immunized more than 5 years ago, or
with incomplete vaccination:
By IM injection,
ADULT and CHILD, 1 dose of 0.5 mL
each, given on days 0, 3, 7, 14, and 28
(for a total of 5 doses); or, alternatively,
2 doses on day 0 (one in each deltoid
or thigh), followed by 1 dose on days 7
and 21 (for a total of 4 doses).
This is given with Human Rabies
Immunoglobulin (HRIG) at 20 IU/kg of
body weight, administered at the same
time as the first injection for severe
injuries (Note: administer the vaccine
contralaterally to the HRIG
administration site).
By ID injection,
ADULT and CHILD (8-site regimen), 1
dose of 0.1 mL administered at 8
separate sites on day 0 (one in each
upper arm, one in each lateral thigh,
one in each side of the suprascapular
region, and one in each side of the
lower quadrant region of the abdomen),
followed by 1 dose of 0.1 mL in each
upper arm on days 30 and 90; or,
alternatively, (2-site regimen), 1 dose of
0.1 mL at 2 sites on days 0, 3, 7, and
28 (for total of 8 doses).
This is given with Human Rabies
Immunoglobulin (HRIG) at 20 IU/kg of
body weight, administered at the same
time as the first injection for severe
injuries (Note: administer the vaccine
contralaterally to the HRIG
administration site).
Post-exposure treatment against rabies in fully
immunized individuals:
By IM or ID injection, ADULT and CHILD,
one 0.5 mL dose given on day 0 and
another on day 3.
NOTE: Check the antibody response to post-
exposure immunization course in
immunocompromised people as further
doses may be needed.
Dose Adjustments: No information found.
Precautions:
Caution in individuals with history of systemic
allergic reaction to any ingredient in the
Page | 228
vaccine; acute febrile illness (postpone
all vaccinations until patient is well);
once initiated, rabies prophylaxis should
not be interrupted nor discontinued
because of development of local or mild
systemic reactions (the risk of acquiring
rabies should be weighed before
deciding to discontinue vaccination).
NOTE: immediate treatment for
anaphylaxis or hypersensitivity reactions,
including epinephrine 1:1000 should be
available during vaccine use.
NOTE: If schedule requires rabies vaccine and
rabies immunoglobulin to be
administered at the same time, they
should be given using separate syringes
and separate sites.
Adverse Drug Reactions:
Common: Abdominal pain, allergic reactions,
diarrhea, dizziness, dyspnea, fainting,
headache, lymphadenopathy, malaise,
myalgia, nausea, rash, serum sickness-
like reactions, transient fever, transient
injection site reactions (pain, redness,
itching, swelling or burning, small hard
lump that may persist for some weeks),
vomiting, weakness.
Less Common: Angioedema.
Rare: Neuroparalytic events.
Drug Interactions:
Monitor closely with:
Other vaccines and immunoglobulins – these
can influence the ability of vaccines to
induce an immune response (give a live
vaccine on the same day or not < 4
weeks apart from another live vaccine).
Avoid concomitant use with:
Anti-infectives – avoid giving live vaccines with
anti-infectives, especially if they are
active against the organism in the
vaccines, as the effectiveness of
vaccines may be reduced, preventing an
immune response.
Immunosuppressive agents and during
radiation therapy – these may interfere
with the active antibody response to
rabies vaccine, and increase the risk of
the patient developing rabies.
ANTI-INFECTIVES
Administration:
Management of bite wound:
The bite wound must be thoroughly cleansed.
Immediately flush out and wash with
soap and water or detergent to eliminate
the rabies virus at the infection site.
Thoroughly remove all traces of soap
then apply 70% alcohol solution, tincture
or solution of iodine, or, 0.1% quaternary
ammonium solution.
When administered by IM injection, the vaccine
should be given in the deltoid region in
adults and children; the anterolateral
thigh is the preferred site in children < 2
years of age. Do not inject into the
gluteal area.
May also administer by ID injection as an
alternative into the upper or forearm. ID
route must be administered only by
medical staff trained in this technique to
ensure vaccine is delivered by ID and
NOT by SC. Use sterile syringe with fixed
needle (insulin type). Do NOT inject by IV
or SC.
NOTE: There may be a suboptimal response if
a vaccine is injected incorrectly (route or
area); local response may also be
increased; IM injections must be given
slowly to reduce pain.
Reconstitute using the solvent provided. Shake
gently to obtain a homogenous
suspension, appearing as a limpid liquid.
Immediately administer vaccine.
Reconstituted vaccine may be used for
up to 8 hours provided it is maintained
at 2–8oC. Discard unused portions after
8 hours.
STORAGE: Vaccines should be stored within
the safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
See monograph on Human Rabies
Immunoglobulin (HRIG) for other
information.
TETANUS TOXOID
Rx
Inj.: 0.5 mL ampul (IM)
10 mL vial (IM)
A sterile solution of tetanus toxoid in isotonic
sodium chloride solution, which is used
as a booster injection against tetanus.
Indications: Active immunization against
tetanus; tetanus prophylaxis as part of
wound management (e.g., tetanus-prone
wounds and clean wounds).
Contraindication: Known hypersensitivity to the
preparation or any of its components.
Dose:
Management of clean wounds and tetanus-
prone wounds, by IM injection, ADULT,
0.5 mL as a single dose (the dose
schedule will be dependent upon the
immune status of the patient, and the
level of contamination of the wound).
NOTE:
Tetanus prophylaxis in wound
management should be based on the
status of the wound (clean or
contaminated), and the immunization
status of the patient. Wound
management includes proper use of
tetanus toxoid and/or tetanus immune
globulin (TIG), wound cleaning, and (if
required) surgical debridement and the
proper use of antibiotics.
1. For clean wounds, fully immunized
individuals and those whose
primary immunization is complete
(with boosters up to date) do not
require tetanus vaccine.
Individuals whose primary
immunization is incomplete or
whose boosters are not up to date
require a reinforcing dose of
tetanus vaccine (followed by
further doses as required to
Page | 229
ANTI-INFECTIVES
complete the schedule). Non-
immunized individuals (or those
whose immunization status is not
known, or immunized but are now
immunocompromised) should be
given a dose of the vaccine
immediately (followed by
completion of the full course of the
vaccine if records confirm the
need).
2. For tetanus-prone wounds,
management is as for clean
wounds with the addition of a dose
of antitetanus immunoglobulin
given at a different site; the
immunoglobulin is needed only if
the risk of infection is especially
high (e.g., contamination with
manure).
each of 0.5 mL, the first at least 1 year
after completion of the primary course
and the second dose at least 1 year
later.
Reinforcing immunization of adults against
tetanus, by IM injection, ADULT, 2 doses,
each of 0.5 mL, the first 10 years after
completion of the primary course, and
the second dose 10 years later.
Immunization of unimmunized pregnant
women against tetanus, by IM injection,
ADULT, 2 doses, each of 0.5 mL, with an
interval of at least 4 weeks between
each dose (second dose at least 2 weeks
before delivery), followed by a third dose
of 0.5 mL 6 months later; and 2 booster
doses, each of 0.5 mL, the first at least
1 year after completion of the primary
course, and the second dose at least 1
year later.

W/ CLEAN, ALL OTHER Dose Adjustments: No information found.

PRIOR MINOR WOUND WOUNDS
TETANUS Tetanus TIG Tetanus TIG Precautions:
IMMUNI- Toxoid Toxoid IM injections should be given with caution in
ZATION patients with thrombocytopenia or other
Uncertain coagulation disorders; history of Guillain-
or less Yes No Yes Yes Barré syndrome (GBS) (increased risk of
than 3 recurrent GBS after subsequent doses
doses of vaccine).
NOTE: For patients at risk of hemorrhage
following IM injection, administer by IM
No. No No. No
route only if, in the opinion of the
3 or more
physician familiar with the patient's
doses Administe Adminis
bleeding risk, the vaccine can be
r only if ter only
administered by this route with
last dose if last
reasonable safety. Use a fine needle (23
was given dose
gauge or smaller) and apply firm
> 10 was
pressure to the site (without rubbing) for
years given >
at least 2 minutes.
prior 5 years
If the patient receives anti-hemophilia or
prior
other similar therapy, intramuscular
vaccination can be scheduled shortly
after such therapy is administered.
Primary immunization of unimmunized
Patients on anticoagulant therapy
adolescents and adults (including
should be considered to have the same
women of child-bearing age) against
bleeding risk.
tetanus, by IM injection, ADULT and
ADOLESCENT, 3 doses, each of 0.5 mL,
ANTITETANUS IMMUNOGLOBULIN. If schedule
with an interval of not < 4 weeks
requires tetanus vaccine and
between the first and second doses and
antitetanus immunoglobulin to be
6 months between the second and third
administered at the same time, they
doses; followed by 2 reinforcing doses,

Page | 230
ANTI-INFECTIVES
should be administered using separate
syringes and separate sites.
Adverse Drug Reactions:
Common: Nausea.
Less Common: Fainting, fever, lethargy,
myalgia, rash, transient injection site
reactions (pain, redness, itching,
swelling, burning, small hard lump that
may persist for some weeks).
Rare: Allergic reactions, including anaphylaxis;
disturbances in EEG, Guillain-Barré
syndrome, headache, hypotension,
malaise, peripheral neuropathy,
urticaria.
Drug Interaction:
Avoid concomitant use with:
Immunosuppressive agents (e.g., therapeutic
doses of corticosteroids or
antineoplastics) and during radiation
therapy – these may decrease antibody
response to inactivated vaccines.
NOTE: Any agent which is active against the
bacterial or viral strain present in the
vaccine may interfere with the
development of a protective immune
response, but treatment with
antibacterials is not a contraindication to
immunization.
Administration: Inject IM in the area of the
anterolateral thigh or deltoid muscle.
The vaccine should not be injected into
the gluteal area or areas where there
may be a major nerve trunk.
NOTE: Parenteral products should be
inspected visually for discoloration
and/or extraneous particulate matter
prior to administration whenever
solution and container permit. It should
not be used if particulate matter or
discoloration is found.
STORAGE: Vaccines should be stored within
the safe temperature range of 2-8°C.
Freezing is the most common cause of
vaccine damage; do not use a defrosted
vaccine unless freezing is the
recommended storage condition.
Pregnancy Category: C
TYPHOID VACCINE
Rx
Oral: live attenuated S. typhi (not less than
109) viable strain, enteric-coated
tablet (encapsulated)
Inj.: 25 micrograms Vi-capsular polysaccharide
S. typhi in 0.5 mL pre-filled syringe (IM)
A bacterial vaccine containing virulent strains
of Salmonella typhi that confer immunity
by the provocation of a local immune
response in the intestinal tract induced by
oral ingestion of a live strain with
subsequent aborted infection.
Indication: Active immunization against
typhoid fever caused by Salmonella
typhi
Contraindications: Hypersensitivity to any
component of the vaccine; acute febrile
illness; congenital or acquired
immunodeficient state
Dose:
Primary immunization, by mouth, ADULT and
CHILD ≥6 years, 1 capsule on alternate
days for 4 doses, completed at least 1
week prior to expected exposure; by IM
injection, ADULT and CHILD ≥2 years,
0.5 mL at least 2 weeks prior to
expected exposure.
Reimmunization, by mouth, ADULT and CHILD
≥6 years, repeat full course of primary
immunization every 5 years; by IM
injection, ADULT and CHILD ≥2 years,
0.5 mL every 2 years.
Precautions:
Anaphylactoid or hypersensitivity reactions
(immediate treatment, including
epinephrine 1: 1,000 should be
available during vaccine use; syncope;
Page | 231
ANTI-INFECTIVES
acute illness; bleeding disorders, Drugs that reduce diagnostic effect of
including thrombocytopenia; typhoid Tuberculin Test:[separate administration
fever. by at least 4–6 weeks]
Pregnancy (animal reproduction studies have Drugs that reduce therapeutic effect of Typhoid
not been conducted); Vaccine:
Lactation (not known if excreted into Antibiotics (check product/ drug
breastmilk). information); Gentian Violet;
Metronidazole (Topical); Neomycin;
Adverse Drug Reactions: Polymyxin B; Povidone-Iodine; Rifaximin;
Common: Silver Nitrate; Silver Sulfadiazine;
Following Inj. administration: Malaise, Sulfacetamide (Topical); Tobramycin
headache, generalized ache, pruritus, (Ophthalmic) [live attenuated Ty21a
nausea, vomiting, injection site strain only; [postpone vaccination until
reactions (tenderness, pain, induration, at least 3 days after cessation of
erythema, swelling), muscle tenderness, antibacterial agents]
myalgia, fever Azathioprine [avoid doses >3 mg/kg
Following Oral administration: daily] Corticosteroids, Systemic [avoid
Headache, skin rash, abdominal pain, doses greater than an equivalent of 2
nausea, diarrhea, vomiting mg/kg or 20 mg/day of prednisone for
≥2 weeks]
Less Common: Dimethyl fumarate
Following Inj. administration: Abdominal Immune Globulins [consult full
pain, anaphylaxis, angioedema, interaction monograph for dose interval
arthralgia, asthma, diarrhea, dizziness, recommendations]
flu like symptoms, Guillain-Barré Immunosuppressants [except
syndrome, hypotension, inflammation at Azathioprine; Beclomethasone (Oral
injection site (angioedema, urticaria), Inhalation); Betamethasone (Systemic);
intestinal perforation (jejunum), Budesonide (Systemic); Budesonide,
hypersensitivity reaction, loss of (Systemic and Oral Inhalation);
consciousness, lymphadenopathy, Corticotropin; Cortisone;
malaise, neck pain, serum sickness, skin Dexamethasone (Systemic); Fluticasone
rash, syncope (with and without (Oral Inhalation); Hydrocortisone
convulsions), tremor, urticaria, (Systemic); Mercaptopurine;
vasodilation, weakness Methotrexate; Methylprednisolone;
Following Oral Administration: Prednisolone (Systemic); Prednisone;
Anaphylaxis, demyelinating disease, Triamcinolone (Systemic) [separate
myalgia, pain, rheumatoid arthritis, administration by at least 3 months];
sepsis, urticaria, weakness Mercaptopurine [avoid doses >1.5
mg/kg daily]
Drug Interactions: Methotrexate [avoid doses >0.4 mg/kg
Avoid concomitant use with: weekly]
Drugs that increase risk of adverse or toxic
effects Administration:
of Typhoid Vaccine: Azathioprine, For oral administration, swallow capsules
Corticosteroids (Systemic), Dimethyl whole soon after placing into mouth
Fumarate (vaccinal infection), with a cold or lukewarm beverage
Immunosuppressants, Mercaptopurine, (≤37˚C/98.6˚F). Do NOT chew or open
Methotrexate capsule.

Page | 232
ANTI-INFECTIVES
To be taken 1 hour prior to a meal. Avoid
alcohol 1 hour before or 2 hours after
administration to prevent disruption of
the enteric coating.

For IM administration, administer as a single

0.5 mL (25 micrograms) injection into the
deltoid muscle. Younger children may also
receive the dose in the anterolateral thigh.
Do NOT inject into the gluteal muscle. Do
NOT administer by IV.

Administer while patient is seated or lying

down to prevent syncope related injuries.

NOTE: For patients at risk of hemorrhage

following IM injection, administer by IM
only if, in the opinion of the physician
familiar with the patient's bleeding risk,
the vaccine can be administered by this
route with reasonable safety. Use a fine
needle (23 gauge or smaller) and apply
firm pressure to the site (without rubbing)
for at least 2 minutes.

If the patient receives anti-hemophilia or

other similar therapy, intramuscular
vaccination can be scheduled shortly after
such therapy is administered. Patients on
anticoagulant therapy should be
considered to have the same bleeding
risks and treated as those with clotting
factor disorders.

Pregnancy Category: C

Page | 233
MUSCULO-SKELETAL SYSTEM
MUSCULO-SKELETAL
SYSTEM
ANTIINFLAMMATORY AND
ANTIRHEUMATIC PRODUCTS
NON-SELECTIVE COX INHIBITORS
ASPIRIN
Rx
Oral: 80 mg and 100 mg tablet
An irreversible, cyclooxygenase (COX) inhibitor,
which prevents platelet aggregation, and
is useful in the long- term management
of MI and the prevention of further
attacks.
Indications: Pain and inflammation associated
with musculoskeletal and joint
disorders; juvenile rheumatoid arthritis
Contraindications: Children and adolescents
<16 years (risk of Reye syndrome);
active peptic ulceration or bleeding GI
ulcers; hemophilia and other bleeding
disorders; aspirin-sensitive asthma;
thrombocytopenia; ulcerative colitis;
lactating mothers; acute hemorrhagic
stroke or intracerebral bleeding
Dose:
Pain and inflammation associated with
musculoskeletal and joint disorders, by
mouth, ADULT, initially 2.4–3.6 g daily
in divided doses; usual maintenance
dose, 3.6–5.4 g daily.
Juvenile rheumatoid arthritis, by mouth, CHILD,
80 to 100 mg/kg daily in 5 or 6 divided
doses, up to 130 mg/kg daily in acute
exacerbations if necessary.
Dose Adjustment:
Page | 234
Renal Impairment:
For mild-to-moderate renal impairment, dose
adjustments are not necessary.
For severe impairment, the drug is not
recommended.
Hepatic Impairment:
Avoid use in severe liver disease.
Precautions:
Increased risk of gastritis and GI bleeding;
Asthma;
Urticaria;
Allergic disease;
Uncontrolled hypertension;
Renal impairment (avoid use; due to sodium
and water retention – deterioration in renal
function may increase risk of GI bleeding);
Hepatic impairment (avoid in severe
impairment – there is increased risk of GI
bleeding);
G6PD-deficiency;
Dehydration;
Gout;
Elderly;
Neonates (regular use of high doses could
impair platelet function and produce
hypoprothrombinemia if neonatal vitamin K
stores are low; possible risk of Reye
syndrome).
Pregnancy (avoid analgesic doses, if possible,
in the last few weeks).
Adverse Drug Reactions:
Common: Abdominal pain, asymptomatic
blood
loss, back pain, bleeding time increased,
diarrhea, dyspepsia, dyspnea, epistaxis,
fatigue, GI irritation, headache, malaise,
melena, nausea, vomiting
Less Common: Anorexia, asthenia, confusion,
dizziness, fever, flushing, gastritis,
hemorrhage rectum, hemorrhoids, thirst,
hypoglycemia (children), hypotension,
myalgia, palpitations, syncope,
tachycardia, tinnitus, vertigo
Rare: Arrhythmia, convulsions, deafness,
edema, GI ulcer and perforation,
intracranial hemorrhage,
MUSCULO-SKELETAL SYSTEM
hypersensitivity reactions, including
Stevens-Johnson syndrome; interstitial
nephritis, iron-deficiency anemia,
myocarditis, paresthesia, renal
insufficiency, seizures,
thrombocytopenia, toxic epidermal
necrolysis
Drug Interactions:
Monitor closely with drugs that:
Enhances therapeutic effect of Aspirin:
Valproic Acid (blood coagulation; platelet
function)
Enhances therapeutic effect of the following
drugs:
Oral Hypoglycemics, Phenytoin, Valproic
Acid
Increases risk of adverse or toxic effects of
Aspirin:
Corticosteroids (GI bleeding and
ulceration)
Increases risk of adverse or toxic effects of the
following drugs:
Anticoagulant Therapy, e.g., Heparin,
Warfarin (bleeding), Valproic Acid
Avoid concomitant use with drugs that:
Increases excretion of Aspirin:
Antacids, e.g., Aluminum and
Magnesium Hydroxide
Increases risk of adverse or toxic effects of the
following drugs:
ACE Inhibitors, e.g., Enalapril (renal
impairment when aspirin is given in
doses of >300 mg daily), NSAIDs, e.g.,
Ibuprofen, Naproxen (gastric ulceration)
Reduces therapeutic effect of Aspirin:
NSAIDs, e.g., Ibuprofen, Naproxen (anti-
platelet activity; cardioprotective effect)
Reduces therapeutic effect of the following
drugs:
ACE Inhibitors, e.g., Enalapril
(hyponatremic and hypotensive effect),
Diuretics, e.g., Spironolactone (inhibition
of renal prostaglandins)
Administration: Take tablets from packaging
Immediately before use. Should be
taken with food or immediately after
meals.
Pregnancy Category: C; D in 3rd trimester
ATC Code: B01AC06
See under Antithrombotics in Blood and Blood
Forming Organs for more information.
CELECOXIB
Rx
Oral: 100 mg, 200 mg and 400 mg capsule
A diaryl-substituted, pyrazole-derived, selective
cyclo-oxygenase-2 (COX-2) inhibitor,
which is associated with less GI side
effects and susceptibility to bruising and
bleeding than nonselective NSAIDs.
Indications: Relief of the signs and symptoms
of osteoarthritis, ankylosing spondylitis
and rheumatoid arthritis; and short-term
(≤7 days) management of moderate to
severe acute injury (post-operative,
musculo- skeletal or soft tissue), or
following dental extraction.
Contraindications: Known hypersensitivity to
other NSAIDs, aspirin, sulfonamides or
any component of the formulation;
active GI disease or bleeding; heart
failure, angina, peripheral arterial
disease or cerebrovascular disease; the
perioperative setting of Coronary Artery
Bypass Graft Surgery; the third trimester
of pregnancy (risk of premature closure
of the ductus arteriosus and prolonged
parturition); breastfeeding (due to
potential for serious adverse reactions in
nursing infants); severe liver impairment
or active liver disease; severe renal
impairment; inflammatory bowel
disease; known hyperkalemia.
Page | 235
MUSCULO-SKELETAL SYSTEM
Dose:
NOTE: Risk of cardiovascular adverse events is
dose-related; do not use >200 mg daily
long-term; use the lowest effective dose
for the shortest duration of time,
consistent with patient treatment goals.
Acute dental pain, by mouth, ADULT, 400 mg,
followed by an additional 200 mg if
needed on Day 1; maintenance dose:
200 mg twice daily as needed, not to
exceed 7 days.
Ankylosing spondylitis, by mouth, ADULT, up to
200 mg daily, in one or two divided
doses twice daily.
Osteoarthritis, by mouth, ADULT, 200 mg daily
as a single dose or as two divided doses.
Pain, acute (post-operative, musculoskeletal or
soft tissue), by mouth, ADULT, 400 mg
as a single dose on the 1st day, then 200
mg once or twice daily if needed
(maximum: 7 days treatment).
Rheumatoid arthritis, by mouth, ADULT, 100
mg twice daily; may be increased to 200
mg twice daily (short-term use only).
Dose Adjustment:
Elderly:
Initiate at the lowest recommended dose of the
medicine in patients weighing <50 kg
(the AUC in elderly patients may be
increased by 50%).
Renal Impairment:
For mild-to-moderate renal impairment,
adjustment may not be necessary (but
pre-existing renal impairment increases
the risk of NSAID-induced impairment);
for severe impairment, celecoxib is
contraindicated.
Hepatic Impairment:
For mild-to-moderate hepatic impairment,
dose reduction by 50% is warranted; for
severe impairment, Celecoxib is
contraindicated.
Precautions:
WARNING:
Cardiovascular risk – NSAIDs are associated
with an increased risk of serious (and
potentially fatal) adverse
cardiovascular events, including MI,
stroke, ischemic heart disease,
cerebrovascular disease and
Page | 236
congestive heart failure. All NSAIDs
may have a similar risk. This risk may
increase with duration of use. Patients
with cardiovascular disease or risk
factors for cardiovascular disease may
be at greater risk.
Gastrointestinal risk – NSAIDs cause an
increased risk of serious GI adverse
events, including bleeding, ulceration,
and perforation of the stomach or
intestines, which can be fatal. These
events can occur at any time during
their use and without warning
symptoms. Elderly patients are at
greater risk for serious GI events.
Pre-existing renal impairment increases the
risk of NSAID-induced impairment.
In patients with hypertension, congestive heart
failure or cardiovascular disease
(NSAIDs can promote sodium and fluid
retention in a dose-dependent manner,
through reduction in glomerular filtration
rate and renal blood flow, which can
result in increased BP and/or
exacerbation of CHF); Use with caution
among patients with history of GI
diseases or bleeding, vitamin K
deficiency, or hypoprothrombinemia;
may exacerbate existing hepatic or renal
insufficiency.
NSAIDs which inhibit prostaglandin
biosynthesis interfere with platelet
function to varying degrees (patients
who may be adversely affected are those
on anticoagulants, or suffering from
hemophilia or platelet disorders).
Anaphylactoid reactions may be observed;
asthma, especially with rhinitis or nasal
polyps (NSAIDs may increase the risk of
bronchospasm); some NSAIDs are
associated with persistent urinary
symptoms, hematuria, or cystitis;
monitor stool for blood and kidney
function if NSAIDs are used chronically;
the elderly (increased risk of adverse
effects, in particular heart failure, GI
ulceration and renal impairment).
Pregnancy (there may be an increased risk for
miscarriage; risk appears highest when
the NSAIDs are taken around the time of
conception; this is contraindicated in the
third trimester); women (reconsider
MUSCULO-SKELETAL SYSTEM
NSAID use if planning for pregnancy, as significant decrease in renal function.
NSAIDs may impair fertility by preventing NSAIDs may also reduce their
or delaying ovulation – reversible). antihypertensive effect.
Patient response to NSAIDs is variable. Switch Agents with antiplatelet properties (e.g.,
to another preparation if response is NSAIDs, SSRIs) – an increased risk of
inadequate. bleeding may occur (NSAIDs may
enhance the adverse effect of these
Adverse Drug Reactions: drugs).
Common: Abdominal pain, back pain, cough, Aminoglycosides – NSAIDs may decrease the
diarrhea, dizziness, dyspepsia, fever, excretion of these drugs.
flatulence, headache, insomnia, Angiotensin II receptor blockers – these may
nasopharyngitis, nausea, peripheral enhance the adverse effect of NSAIDs,
edema, pharyngitis, rash, rhinitis,
specifically a significant decrease in
sinusitis, upper respiratory tract
renal function. NSAIDs may also reduce
infection, vomiting.
their antihypertensive effect.
Less Common: Alopecia, anemia, angina, Anticoagulants – their anticoagulant effect
anorexia, anxiety, arthrosis, bradycardia, may be enhanced by NSAIDs; at an
bronchospasm, cellulitis, chest pain, increased risk of serious bleeding.
constipation, cystitis, depression, Benzodiazepines and antidepressants – their
dermatitis, dryness of skin, dysphagia,
effects may be altered by NSAIDs.
dyspnea, facial edema, fatigue,
Beta-blockers – NSAIDs may diminish the
gastroesophageal reflux, GI ulcer,
antihypertensive effect of these drugs.
hypercholesterolemia, hyperglycemia, Digoxin – NSAIDs may increase the serum
hypertension, hypokalemia, MI, concentration of this drug.
migraine, myalgia, nervousness, pain Diuretics (e.g., thiazide diuretics, and
palpitations, paresthesia, potassium-sparing diuretics) – their
photosensitivity, pruritus, sinus therapeutic effect may be diminished by
tachycardia, somnolence, tinnitus,
NSAIDs.
urinary frequency, urticaria, ventricular
Haloperidol – NSAIDs may enhance the
hypertrophy, vertigo, xerostomia. adverse effect of this drug.
Rare: Acute renal failure, agranulocytosis, Quinolone antibiotics – NSAIDs may enhance
anaphylactoid reactions, angioedema, the neuroexcitatory and/or seizure-
aplastic anemia, cerebrovascular potentiating effect of these drugs.
accidents, CHF, cholelithiasis, colitis,
DVT, erythema multiforme, esophageal Avoid concomitant use with:
perforation, exfoliative dermatitis, Aspirin – concomitant administration with this
gangrene, GI bleeding, hepatic failure drug results in an increased rate of GI
and necrosis, hepatitis, hypoglycemia, ulceration or other complications.
hyponatremia, intestinal obstruction and Loop diuretics – their prostaglandin-mediated
perforation, intracranial hemorrhage, effect may be antagonized by NSAIDs.
jaundice, leukopenia, pancreatitis, Other NSAIDs – the use of celecoxib in addition
pancytopenia, pulmonary embolism, to any other NSAID is not recommended
renal papillary necrosis, sepsis, Stevens- because of the absence of any evidence
Johnson syndrome, suicide, syncope, demonstrating synergistic benefits and
taste disturbance, thrombocytopenia, the potential for additive adverse
thrombophlebitis, toxic epidermal reactions.
necrolysis, vasculitis, ventricular Vitamin K antagonists (e.g., warfarin) –
fibrillation. anticoagulant effect may be enhanced
Drug Interactions: by NSAIDs; increased risk of serious
Monitor closely with: bleeding.
ACE inhibitors – these may enhance the Administration: May be administered without
adverse effect of NSAIDs, specifically a regard to meals.

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MUSCULO-SKELETAL SYSTEM
NOTE: GI absorption is delayed by food and milk. Dose Adjustments:
Pregnancy Category: C; D in the 3rd trimester or Renal and Hepatic Impairment:
near delivery. The dose should be kept as low as possible;
use with caution.
ATC Code: M01AH01
Precautions:

WARNING:
Cardiovascular risks – NSAIDs are associated
IBUPROFEN with an increased risk of adverse
Rx cardiovascular thrombotic events,
including fatal MI and stroke.
Gastrointestinal events – NSAIDs may
Oral: 200 mg and 400 mg tablet
increase risk of GI irritation,
100 mg/5 mL suspension, 60 mL
inflammation, ulceration, bleeding and
perforation.
A propionic acid-derived, nonselective,
nonsteroidal anti-inflammatory
medicine, which is useful for the
Renal impairment (monitor renal function; may
management of pain due to
cause sodium and water retention;
inflammation.
deterioration in renal function possibly
leading to renal failure); hepatic
Indications: Acute pain and inflammation in
impairment (increased risk of GI
rheumatic diseases and other
bleeding and can cause fluid retention;
musculoskeletal disorders; mild to
avoid use in severe liver disease);
moderate pain, including dysmenorrhea
elderly, in allergic disorders; cardiac
and headache; pain in children; acute
disease; coagulation defects.
migraine attack.
Pregnancy (avoid use unless the potential
benefit outweighs risk; third trimester:
Contraindications: Known hypersensitivity to
with regular use, there is increased risk
ibuprofen and other NSAIDs, or any the
of closure of fetal ductus arteriosus in
components of the formulation; should
utero, and possible persistent
not be given to patients with active
pulmonary hypertension in new-born;
peptic ulceration; should preferably not
may result in delayed onset and an
be used in those with a history of the
increase in duration of labor);
disease.
breastfeeding (amount is too small to be
harmful; short courses safe in usual
Dose:
doses).
Mild to moderate pain, pyrexia and
inflammatory musculoskeletal
Adverse Drug Reactions:
disorders, by mouth, ADULT, 1.2-1.8 g
Common: Diarrhea, dizziness, dyspepsia, GI
daily in 3-4 divided doses, increased if
ulceration or bleeding, headache,
necessary to maximum 2.4 g daily (3.2 g
hemorrhage, hypertension, nausea,
daily in inflammatory disease);
raised liver enzymes, salt and fluid
maintenance dose of 0.6-1.2 g daily may
retention, vomiting.
be sufficient.
Less Common: Bronchospasm, confusion,
Pain in CHILD (not recommended for children
esophageal ulceration, heart failure,
<7 kg), by mouth, 20-40 mg/kg daily in
hyperkalemia, rash, renal impairment.
divided doses; or CHILD 8-12 years, 200
Rare: Acute renal failure, aseptic meningitis,
mg 3-4 times daily; CHILD 3-7 years, 100
blood dyscrasias, blurred vision, colitis,
mg 3-4 times daily; CHILD 1-2 years, 50
cystitis, fluid retention, hepatitis,
mg 3-4 times daily.
anaphylactic and anaphylactoid

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MUSCULO-SKELETAL SYSTEM
reactions, interstitial nephritis, MI,
nephrotic syndrome, photosensitivity
reaction, Stevens-Johnson syndrome,
stroke, tinnitus, toxic epidermal
necrolysis, vertigo.
Drug Interactions:
Monitor closely with:
ACE inhibitors – NSAIDs may reduce
antihypertensive effect of ACE inhibitors,
and may increase the risk of renal
impairment and hyperkalemia.
Angiotensin II receptor blockers – these may
enhance the adverse effect of NSAIDs;
may result in significant decrease in
renal function; NSAIDs may also
diminish the antihypertensive effect of
these drugs.
Aspirin – ibuprofen can reduce the antiplatelet
activity of low-dose aspirin and may
reduce or negate its cardioprotective
effect.
Atenolol, ciprofloxacin and levofloxacin –
possibly increased risk of convulsions.
Corticosteroids, Oral (e.g., hydrocortisone) –
these increase the risk of gastric
ulceration with NSAIDs.
Digoxin – possible exacerbation of heart
failure, reduced renal function and
increased plasma digoxin concentration.
Diuretics (e.g., loop diuretics and thiazide
diuretics) – NSAIDs reduce renal
function and may diminish diuretic
effect; risk of nephrotoxicity is increased.
Other NSAIDs – enhanced adverse effects.
Avoid concomitant use with:
Alendronate – this may increase the risk of
gastric ulceration with NSAIDs.
Antihypertensives (e.g., beta blockers, ARBs,
and nitrates) – NSAIDs may increase BP;
possible reduction of hypotensive effect.
Drugs affecting clotting process (e.g.,
ketorolac) – NSAIDs can cause GI
bleeding and affect platelet function;
possibly increased risk of bleeding.
Drugs which are renally excreted (e.g.,
calcineurin inhibitors) – NSAIDs can
impair renal function; possibly increased
risk of adverse effects of these drugs.
Drugs which increase potassium concentration
(e.g., amiloride and triamterene) –
NSAIDs can cause hyperkalemia;
combination with these drugs may
increase this risk.
Vitamin K antagonists (e.g., warfarin) –
anticoagulant effect may be enhanced
by NSAIDs; increased risk of serious
bleeding.
Administration: Should be taken with food.
Pregnancy Category: C, prior to 30 weeks
gestation; D, ≥30 weeks gestation.
ATC Code: M01AE01
MEFENAMIC ACID
Rx
Oral: 250 mg and 500 mg tablet/capsule
A fenamate-derived (anthranilic acid),
nonsteroidal anti-inflammatory
medicine, which possesses greater anti-
inflammatory and analgesic properties
than ibuprofen or aspirin.
Indications: Symptomatic relief of acute pain
and inflammation; for muscular,
traumatic and dental pain; headache of
most etiology and postoperative and
postpartum pain; the symptomatic relief
of dysmenorrhea; menorrhagia due to
dysfunctional causes or the presence of
an IUD when organic pelvic pathology
has been excluded; premenstrual
syndrome.
Contraindications: Hypersensitivity or ASA
allergy; history of aspirin triad; patients
with inflammatory bowel disease, GI
ulcers and history of GI bleeding or
perforation, related to NSAID therapy;
active or history of recurrent peptic ulcer
or hemorrhage; severe heart failure,
hepatic failure and renal failure; pain
treatment after coronary artery bypass
surgery; during the last trimester of
pregnancy.
Dose:
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MUSCULO-SKELETAL SYSTEM
Dysmenorrhea, by mouth, ADULT, 500 mg 3
times daily, to be administered on the
onset of menstrual pain and continue
while symptoms persist according to the
clinical judgment of the physician.
Menorrhagia, by mouth, ADULT, 500 mg 3
times daily, starting with the onset of
bleeding and associated symptoms and
continued according to the clinical
judgment of the physician.
Mild to moderate pain, by mouth, ADULT, 500
mg 3 times daily, in adults and
adolescents >14 years.
Premenstrual syndrome, by mouth,
ADULT, 500 mg 3 times daily, starting
with the onset of symptoms and
continued until the anticipated cessation
of symptoms according to the judgment
of the physician.
Dose Adjustments:
Renal and Hepatic Impairment:
Use drug with caution for mild to moderate
impairment; for severe impairment, the
patient should be referred to a specialist.
Precautions:
WARNING:
Cardiovascular risks – NSAIDs are associated
with an increased risk of adverse
cardiovascular thrombotic events,
including fatal MI and stroke.
Gastrointestinal events – NSAIDs may
increase risk of GI irritation,
inflammation, ulceration, bleeding and
perforation.
Undesirable effects may be minimized by using
the lowest effective dose for the shortest
duration necessary to control symptoms;
anemia, agranulocytosis, and Coombs’-
positive (hemolytic anemia are seen with
prolonged use; should not be given for
longer than 7 days).
Use with caution among patients with history of
GI diseases or bleeding; hepatic and
renal disease, hypoprothrombinemia or
vitamin K deficiency; use with caution in
patients with hypertension, CHF and
cardiovascular disease; may adversely
affect BP control; anaphylactoid
Page | 240
reactions may be seen; caution is
required for patients suffering, or with a
previous history of, bronchial asthma
(may precipitate bronchospasm).
Patient’s response to NSAIDs is variable,
switch to another preparation if the
response is inadequate; monitor stool
for blood and kidney function if NSAIDs
are to be used chronically (patients on
prolonged therapy should be kept under
surveillance with particular attention to
liver dysfunction, rash, blood dyscrasias
or development of diarrhea).
Elderly (increased frequency of adverse
reactions to NSAIDs, such as GI bleeding
and perforation).
Pregnancy (avoid during last trimester).
Adverse Drug Reactions:
Common: Diarrhea, dizziness, dyspepsia, GI
ulceration or bleeding, headache,
hemorrhage, hypertension, nausea,
raised liver enzymes, salt and fluid
retention, vomiting.
Less Common: Bronchospasm, confusion,
esophageal ulceration, heart failure,
hyperkalemia, rash, renal impairment.
Rare: Similar to Ibuprofen; see under
Ibuprofen.
Drug Interactions:
Monitor closely with:
ACE inhibitors – NSAIDs may reduce
antihypertensive effect of ACE inhibitors,
and may increase risk of renal
impairment and hyperkalemia.
Angiotensin II receptor blockers – these may
enhance the adverse effect of NSAIDs;
may result in significant decrease in
renal function; NSAIDs may also
diminish the antihypertensive effect of
these drugs.
Corticosteroids, Oral – these increase the risk
of gastric ulceration with NSAIDs.
Diuretics (e.g., loop diuretics and thiazide
diuretics) – NSAIDs reduce renal
function and may diminish diuretic
effect; risk of nephrotoxicity is increased.
Other NSAIDs – enhanced adverse effects.
MUSCULO-SKELETAL SYSTEM
Avoid concomitant use with:
Alendronate – this may increase the risk of
gastric ulceration with NSAIDs.
Antihypertensives (e.g., beta blockers, ARBs
and nitrates) – NSAIDs may increase BP;
possible reduction of hypotensive effect.
Drugs affecting clotting process (e.g.,
ketorolac) – NSAIDs can cause GI
bleeding and affect platelet function;
possibly increased risk of bleeding.
Drugs which are renally excreted (e.g.,
calcineurin inhibitors) – NSAIDs can
impair renal function; possibly increased
risk of adverse effects of these drugs.
Drugs which increase potassium concentration
(e.g., amiloride and triamterene) –
NSAIDs can cause hyperkalemia;
combination with these drugs may
increase this risk.
Vitamin K antagonists (e.g., warfarin) –
anticoagulant effect may be enhanced
by NSAIDs; increased risk of serious
bleeding.
Administration: Should be taken with food, or
taken immediately after meals.
Pregnancy Category: C; D if used for prolonged
periods, or near term.
ATC Code: M01AG01
NAPROXEN
Rx
Oral: 250 mg base (275 mg) and 500 mg
base (550 mg) tablet (as sodium salt)
A naphthylpropionic acid-derived, nonsteroidal
anti-inflammatory medicine that inhibits
prostaglandin synthesis; it is
pharmacologically related to ibuprofen
but has a longer half-life allowing for
twice daily dosing.
Indications: Rheumatoid arthritis;
osteoarthritis; ankylosing spondylitis;
juvenile idiopathic arthritis; for the relief
of signs and symptoms of tendonitis and
bursitis; acute gout; management of
pain due to inflammation (e.g., period
pain, migraine); management of primary
dysmenorrhea; inflammatory joint pain.
Contraindications: Known hypersensitivity to
naproxen, aspirin, other NSAIDs, or any
component of the formulation;
treatment of perioperative pain in the
setting of Coronary Artery Bypass Graft
surgery; active peptic ulcers; active GI
inflammatory disease.
Dose:
Acute gout, by mouth, ADULT, initial 750 mg,
followed by 250 mg every 8 hours until
the attack subsides.
Acute musculoskeletal disorders, by mouth,
ADULT, 500 mg initially, then 250 mg 2-
3 times a day.
Ankylosing spondylitis, osteoarthritis,
rheumatoid arthritis, by mouth, ADULT,
500 mg-1 g daily in 2 divided dose; may
increase to 1.5 g daily of naproxen base
if tolerating well and clinically indicated
(for a limited time period, <6 months).
For extended-release tablets, initial 750
mg-1 g once daily; may temporarily
increase to 1.5 g of naproxen base if
tolerating well and clinically indicated.
Dysmenorrhea, by mouth, ADULT, 500 mg
initially, followed by 250 mg every 6-8
hours as required.
Inflammatory joint pain, by mouth, ADULT, 500
mg twice daily.
Juvenile idiopathic arthritis, by mouth, CHILD
>2 years, 10 mg/kg/day in 2 divided
doses (up to 15 mg/kg/day has been
tolerated).
Pain (mild to moderate), acute tendonitis,
bursitis, by mouth, ADULT, initial 500
mg, followed by 500 mg every 12 hours
or 250 mg every 6-8 hours (maximum
daily dose: Day 1: 1.25 g naproxen base;
subsequent daily doses should not
exceed 1 g naproxen base).
NOTE: For relief of acute pain, naproxen
sodium may be preferred due to more
rapid absorption and onset.
Dose Adjustments:
Elderly:
Dose adjustments may be necessary.
Page | 241
MUSCULO-SKELETAL SYSTEM
Renal Impairment:
Consider dose reduction in mild impairment.
Avoid use in moderate to severe
impairment.
Hepatic Impairment:
Use drug with caution for mild to moderate
impairment; for severe impairment, the
patient should be referred to a specialist.
Precautions:
WARNING:
Cardiovascular risks – NSAIDs are associated
with an increased risk of adverse
cardiovascular thrombotic events,
including fatal MI and stroke.
Gastrointestinal events – NSAIDs may
increase risk of GI irritation,
inflammation, ulceration, bleeding and
perforation.
Anaphylactoid reactions may occur (do not use
in patients who experience
bronchospasm, asthma, rhinitis, or
urticaria with aspirin or NSAID therapy);
Cardiovascular events (risks may be increased
with the duration of use or pre-existing
cardiovascular risk factors or disease;
use the lowest effective dose for the
shortest duration of time, consistent
with individual patient goals);
CNS effects (it may cause drowsiness,
dizziness, blurred vision and other
neurologic effects which may impair
physical or mental ability); in patients
with history of GI diseases (bleeding or
ulcers), or concurrent therapy with
aspirin, anticoagulants and/or
corticosteroids, smoking, use of alcohol,
the elderly or debilitated patients;
hematologic effects (platelet adhesion
and aggregation may be decreased;
thus prolonging bleeding time);
hyperkalemia (use of NSAID may
increase the risk of hyperkalemia,
particularly in the elderly, diabetics, or
renal disease);
Skin reactions (NSAID use may cause serious
skin reactions; discontinue use at first
sign of skin rash or hypersensitivity);
aseptic meningitis; hepatic impairment;
Page | 242
Renal impairment; hypertension; asthma
(severe bronchospasm may occur);
elderly (may be at higher risk for adverse
effects from NSAIDs).
Pregnancy (naproxen crosses the placenta,
and can be detected in fetal tissue and
the serum of newborn infants following
in utero exposure; NSAID exposure may
result to various anomalies and
deformities); the chronic use of NSAIDs
in women of reproductive age may be
associated with infertility, which is
reversible upon discontinuation);
breastfeeding (small amounts are
excreted into breast milk).
SKILLED TASKS. May impair ability to perform
skilled tasks, for example operating
machinery or driving.
Adverse Drug Reactions:
Common: Abdominal pain, bleeding time
increased, constipation, diaphoresis,
diarrhea, dizziness, drowsiness,
dyspepsia, dyspnea, edema, flatulence,
fluid retention, gross bleeding or
perforation; headache, heartburn,
hemolysis, indigestion, lightheadedness,
nausea, palpitation, pruritus,
pseudoporphyria, rash, skin eruption,
stomatitis, tinnitus, ulcers, vertigo,
Risual disturbance, vomiting.
Rare: Allergic pneumonitis, aplastic anemia,
aseptic meningitis, cognitive
dysfunction, erythema multiforme,
hemolytic anemia, hepatic impairment,
non-peptic GI ulceration, Stevens-
Johnson syndrome, toxic epidermal
necrolysis, ulcerative stomatitis,
vasculitis.
Drug Interactions:
Monitor closely with:
ACE inhibitors – NSAIDs may reduce
antihypertensive effect of ACE inhibitors,
and may increase risk of renal
impairment and hyperkalemia.
Aminoglycosides – NSAIDs may decrease the
excretion of these drugs.
Angiotensin II receptor blockers – these may
enhance the adverse effect of NSAIDs;
may result in significant decrease in
MUSCULO-SKELETAL SYSTEM
renal function; NSAIDs may also
diminish the antihypertensive effect of
these drugs.
Corticosteroids, Oral – these increase the risk
of gastric ulceration with NSAIDs.
Diuretics (e.g., loop diuretics and thiazide
diuretics) – NSAIDs reduce renal
function and may diminish diuretic
effect; risk of nephrotoxicity is increased.
Other NSAIDs – enhanced adverse effects.
Quinolone antibiotics – NSAIDs may enhance
the neuroexcitatory and/or seizure-
potentiating effect of these drugs.

Avoid concomitant use with:

Alendronate – this may increase the risk of
gastric ulceration with NSAIDs.
Antihypertensives (e.g., beta blockers, ARBs
and nitrates) – NSAIDs may increase BP;
possible reduction of hypotensive effect.
Digoxin – its serum concentration may be
increased by NSAIDs.
Drugs affecting clotting process (e.g.,
ketorolac) – NSAIDs can cause GI
bleeding and affect platelet function;
possibly increased risk of bleeding.
Drugs which are renally excreted (e.g.,
calcineurin inhibitors) – NSAIDs can
impair renal function; possibly increased
risk of adverse effects of these drugs.
Drugs which increase potassium concentration
(e.g., amiloride and triamterene) –
NSAIDs can cause hyperkalemia;
combination with these drugs may
increase this risk.
Vitamin K antagonists (e.g., warfarin) –
anticoagulant effect may be enhanced
by NSAIDs; increased risk of serious
bleeding.

Administration: For conventional tablets,

administer with food, milk or antacids to
decrease GI adverse effects (drug may
cause GI upset, bleeding, ulceration and
perforation).

Pregnancy Category: C

ATC Code: M01AE02

Page | 243
NERVOUS SYSTEM
NERVOUS SYSTEM
ANALGESICS
OPIOIDS
TRAMADOL
Rx
Oral: 50 mg capsule (as hydrochloride)
A centrally-acting, synthetic opioid analgesic
that binds to mu opioid receptors and
inhibits reuptake of norepinephrine and
serotonin.
Indications: Treatment of moderate-to-severe,
acute or chronic pain.
Contraindications: Known hypersensitivity to
tramadol and opioids, or any component
of the formulation; comatose patients; in
patients with history of epilepsy; acute
intoxication with alcohol, hypnotics,
centrally-acting analgesics, opioids, or
psychotropic drugs; opioid dependency;
extended-release formulation is
contraindicated in severe hepatic and
renal impairment; suicidal patients.
Dose:
Acute moderate- to- severe pain, by mouth,
ADULT and CHILD >16 years old, 50-
100 mg every 4-6 hours PRN,
(maximum, 400 mg/day);
Chronic moderate-to-severe pain, by mouth,
ADULT and CHILD >16 years old, initially
25 mg every morning, increase by 25-50
mg/day every 3 days as separate doses
up to 50-100 mg every 4-6 hours PRN;
(maximum, 400 mg/day);
NOTE: For child <16 years, safety and efficacy
are not established. For adults >75
years, see Dose Adjustments.
Dose Adjustments:
Page | 244
Renal Impairment:
Reduce dose. For severe renal impairment,
give immediate-release preparation at
50-100 mg PO every 12 hours
(maximum, 200 mg daily). Extended-
release preparation is contraindicated.
Hepatic Impairment:
For severe hepatic impairment, give
immediate-release preparation at 50 mg
PO every 12 hours (maximum, 100
mg/day). Extended-release preparation
is contraindicated.
Elderly >75 years old:
Use with caution in the elderly. Initiate
treatment using the low end of the
range.
Maximum dose, 300 mg/day.
Precautions:
WARNING: Neonatal opioid withdrawal
syndrome can occur after prolonged use
of tramadol during pregnancy. This can
be life-threatening if not recognized and
treated.
Raised intracranial pressure (respiratory
depression due to opioids may be poorly
tolerated and may further increase ICP;
avoid use); hypotension, shock (reduced
blood volume increases hypotensive risk
and the risk of respiratory depression);
biliary colic or surgery (may cause spasm
of the sphincter of Oddi);
Epilepsy or a recognized risk of seizures, e.g.,
head injury, metabolic disorders, alcohol
and drug withdrawal, CNS infections
(increased risk of seizure; the risk
increases with doses exceeding the
recommended range); use with other
respiratory depressants and MAO
Inhibitors; Serotonin syndrome
(potentially life-threatening) may
develop.
Emotional disturbance or depression.
Pregnancy (prolonged use during pregnancy
may cause neonatal withdrawal
syndrome which can be life-
threatening).
Use with caution for obstetrical preoperative
medication or for post-delivery analgesia
in nursing mothers.
NERVOUS SYSTEM
May impair ability to perform skilled or
hazardous tasks.
Elderly (increased risk of adverse effects);
children (more susceptible to respiratory
depression).
Adverse Drug Reactions:
Common: Abdominal pain, anxiety, arthralgia,
back pain, blurred vision, chest pain,
constipation, cough, decreased appetite
and weight, depression, dermatitis,
dizziness, drowsiness, dry mouth,
dyspepsia, dyspnea, headache,
hypesthesia, increased sweating,
influenza-like illness, itch, lethargy,
miosis, nasal congestion, nausea and
vomiting, neck pain, nervousness,
orthostatic hypotension, paresthesia,
pyrexia, respiratory tract infections,
restlessness, sinus congestion,
sneezing, sore throat, urinary retention,
urinary tract infection, vasodilation.
Less Common: Agitation, appendicitis,
bradycardia, bronchospasm,
cholecystitis, cholelithiasis, confusion,
delirium, edema, flushing,
gastroenteritis, hallucinations,
hypertension, hypogonadism,
hypothermia, irritability, migraine, mood
changes, muscle rigidity, myalgia,
myocardial infarction, myoclonus,
palpitations, pancreatitis, paralytic ileus,
pneumonia, raised liver enzymes,
respiratory depression, sedation, sleep
disorder, syncope, tachycardia, tinnitus,
tremor, ureteric or biliary spasm,
urticaria, vertigo, visual disturbances.
Rare: Anaphylaxis, seizures, Syndrome of
Inappropriate Antidiuretic Hormone
(SIADH).
Drug Interactions:
NOTE: CYP-based interactions: tramadol is
metabolized by CYP2D6; administration
with drugs which affect this enzyme may
alter tramadol’s activity or toxicity (see
Appendix).
Monitor closely with:
CNS Depressants (e.g., alcohol, sedatives and
tranquilizers) – these potentiate effects
of opioids, increasing the risk of
respiratory depression, profound
sedation or coma.
Carbamazepine – this induces the metabolism
of tramadol and may reduce its activity.
Drugs which reduce blood pressure (see
Appendix – Table D) – tramadol may
enhance the hypotensive effect of other
drugs.
Drugs that may contribute to serotonin toxicity
(see Appendix – Table F) – tramadol can
contribute to serotonin toxicity; and may
increase likelihood of toxicity when given
concomitantly with these drugs.
Avoid concomitant use with:
Buprenorphine – this blocks opioid receptors;
blocking their therapeutic effect (may
reduce analgesia or precipitate
withdrawal symptoms in opioid-
dependent people).
Naloxone – this antagonizes opioids; reversing
their effects (rapid reversal may
precipitate acute withdrawal syndrome).
Naltrexone – this reversibly blocks opioid
receptors and reduces their effects (may
precipitate withdrawal symptoms at the
start of the treatment).
Ondansetron – may decrease analgesic effect
of tramadol.
Administration: May be taken with or without
food. Swallow whole, do not chew or
crush tablet.
Pregnancy Category: C
ATC Code: N02AX02
NON-OPIOIDS
Rx IBUPROFEN
Oral: 200 mg and 400 mg tablet
100 mg/5 mL suspension, 60 mL
A propionic acid-derived, nonselective,
nonsteroidal anti-inflammatory
Page | 245
NERVOUS SYSTEM
medicine, which is useful for the Renal impairment (monitor renal function; may
management of pain due to cause sodium and water retention;
inflammation. deterioration in renal function possibly
leading to renal failure); hepatic
Indications: Acute pain and inflammation in impairment (increased risk of GI
rheumatic diseases and other bleeding and can cause fluid retention;
musculoskeletal disorders; mild to avoid use in severe liver disease);
moderate pain, including dysmenorrhea elderly, in allergic disorders; cardiac
and headache; pain in children; acute disease; coagulation defects.
migraine attack. Pregnancy (avoid use unless the potential
benefit outweighs risk; third trimester:
Contraindications: Known hypersensitivity to with regular use, there is increased risk
ibuprofen and other NSAIDs, or any of of closure of fetal ductus arteriosus in
the components of the formulation; utero, and possible persistent
should not be given to patients with pulmonary hypertension in new-born;
active peptic ulceration; should may result in delayed onset and an
preferably not be used in those with a increase in duration of labor);
history of the disease. breastfeeding (amount is too small to be
Dose: harmful; short courses safe in usual
Mild to moderate pain, pyrexia and doses).
inflammatory musculoskeletal
disorders, by mouth, ADULT, 1.2-1.8 g Adverse Drug Reactions:
daily in 3-4 divided doses, increased if Common: Diarrhea, dizziness, dyspepsia, GI
necessary, to maximum 2.4 g daily (3.2 ulceration or bleeding, headache,
g daily in inflammatory disease); hemorrhage, hypertension, nausea,
maintenance dose of 0.6-1.2 g daily may raised liver enzymes, salt and fluid
be sufficient. retention, vomiting.
Pain in CHILD (not recommended for children Less Common: Bronchospasm, confusion,
<7 kg), by mouth, 20-40 mg/kg daily in esophageal ulceration, heart failure,
divided doses; or CHILD 8-12 years, 200 hyperkalemia, rash, renal impairment.
mg 3-4 times daily; CHILD 3-7 years, 100 Rare: Acute renal failure, aseptic meningitis,
mg 3-4 times daily; CHILD 1-2 years, 50 blood dyscrasias, blurred vision, colitis,
mg 3-4 times daily. cystitis, fluid retention, hepatitis,
NOTE: Not recommended for children with anaphylactic and anaphylactoid
weight of < 7 kg. reactions, interstitial nephritis, MI,
nephrotic syndrome, photosensitivity
Dose Adjustments: reaction, Stevens-Johnson syndrome,
Renal and Hepatic Impairment: stroke, tinnitus, toxic epidermal
The dose should be kept as low as possible; necrolysis, vertigo.
use with caution.
Drug Interactions:
Precautions: Monitor closely with:
ACE inhibitors – NSAIDs may reduce
WARNING: antihypertensive effect of ACE inhibitors,
Cardiovascular risks – NSAIDs are associated and may increase the risk of renal
with an increased risk of adverse impairment and hyperkalemia.
cardiovascular thrombotic events, Angiotensin II receptor blockers – these may
including fatal MI and stroke. enhance the adverse effect of NSAIDs;
Gastrointestinal events – NSAIDs may may result in significant decrease in
increase risk of GI irritation, renal function; NSAIDs may also
inflammation, ulceration, bleeding and diminish the antihypertensive effect of
perforation. these drugs.

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NERVOUS SYSTEM
Aspirin – ibuprofen can reduce the antiplatelet
activity of low-dose aspirin and may PARACETAMOL
reduce or negate its cardioprotective Rx
effect.
Atenolol, ciprofloxacin and levofloxacin –
Oral: 300 mg and 500 mg tablet
possibly increased risk of convulsions.
120 mg (125 mg)/5 mL
Corticosteroids, Oral (e.g., hydrocortisone) –
syrup/suspension, 60 mL
these increase the risk of gastric
(alcohol-free)
ulceration with NSAIDs.
250 mg/5 mL syrup/suspension, 60 mL
Digoxin – possible exacerbation of heart
(alcohol-free)
failure, reduced renal function and
100 mg/mL drops, 15 mL (alcohol-free)
increased plasma digoxin concentration.
Inj: 10 mg/mL, 50 mL and 100 mL vial
Diuretics (e.g., loop diuretics and thiazide
solution for infusion (IV)
diuretics) – NSAIDs reduce renal
Rectal: 125 mg and 250 mg suppository
function and may diminish diuretic
effect; risk of nephrotoxicity is increased.
A para-aminophenol-derived, weak COX-1 and
Other NSAIDs – enhanced adverse effects.
COX-2 inhibitor that has no significant
anti-inflammatory activity, and is
Avoid concomitant use with:
particularly useful for treating mild to
Alendronate – this may increase the risk of
moderate pain, for reducing fever, and in
gastric ulceration with NSAIDs.
patients where salicylates and other
Antihypertensives (e.g., beta blockers, ARBs,
NSAIDs are contraindicated.
and nitrates) – NSAIDs may increase BP;
possible reduction of hypotensive effect.
Indications: Mild-to-moderate pain, including
Drugs affecting clotting process (e.g.,
dysmenorrhea and tension headache;
ketorolac) – NSAIDs can cause GI
pain relief in osteoarthritis and soft
bleeding and affect platelet function;
tissue lesions; acute migraine attacks;
possibly increased risk of bleeding.
pyrexia.
Drugs which are renally excreted (e.g.,
calcineurin inhibitors) – NSAIDs can
Contraindications: Known hypersensitivity to
impair renal function; possibly increased
paracetamol or any component of the
risk of adverse effects of these drugs.
formulation; severe active liver disease;
Drugs which increase potassium concentration
prolonged or repeated administration in
(e.g., amiloride and triamterene) –
patients with anemia, or cardiac,
NSAIDs can cause hyperkalemia;
pulmonary, hepatic and renal disease.
combination with these drugs may
increase this risk.
Dose:
Vitamin K antagonists (e.g., warfarin) –
Mild-to-moderate pain, pyrexia, by mouth,
anticoagulant effect may be enhanced
ADULT, 0.5-1 g every 4-6 hours
by NSAIDs; increased risk of serious
(maximum, 4 g daily); CHILD 6-12 years,
bleeding.
250-500 mg; CHILD 1-5 years, 120-250
mg; CHILD 3 months-1 year, 60-125 mg
Administration: Should be taken with food.
or 10-15 mg/kg/dose (in children doses
may be repeated every 4-6 hours if
Pregnancy Category: C, prior to 30 weeks
necessary; maximum, 4 doses in 24
gestation; D, ≥30 weeks gestation.
hours); CHILD <3 months, see notes
below.
ATC Code: N02AJ19
By IV injection, ADULT, > 50 kg, 650 mg
every 4 hours or 1,000 mg every 6 hours
(maximum single dose: 1,000 mg per
dose; maximum daily dose: 4 grams
daily); ADULT, <50 kg, 15 mg/kg every 6

Page | 247
NERVOUS SYSTEM
hours or 12.5 mg/kg every 4 hours impairment; renal impairment; (dose-
(maximum single dose: 15 mg/kg/dose related toxicity; avoid large doses, e.g.,
or 750 mg; maximum daily dose: 75 >4 g/day).
mg/kg or 3.75 g); CHILD 2 – 12 years Pregnancy (not known to be harmful);
old, 15 mg/kg every 6 hours or 12.5 breastfeeding (small amount is present
mg/kg per dose every 4 hours in milk; short courses are safe in usual
(maximum single dose: 15 mg/kg/dose dosage; monitor infant).
or 750 mg; maximum daily dose: 75
mg/kg or 3.75 g). Adverse Drug Reactions:
Post-immunization pyrexia, by mouth, INFANT Common: Increased aminotransferases.
2-3 months, 10-15 mg/kg/dose Rare: Acute hepatitis, drug fever,
followed by a second dose, if necessary, hepatocellular necrosis, hypersensitivity
4-6 hours later (warn parents to seek reactions, hypotension, mucosal lesions,
medical advice if pyrexia persists after leukopenia, neutropenia, pancytopenia,
the second dose). renal tubular necrosis,
Treatment of acute migraine attack, by mouth, thrombocytopenia, urticarial or
ADULT, 0.5-1 g at first sign of attack, erythematous rash.
repeated every 4-6 hours if necessary,
(maximum, 4 g daily); CHILD 6-12 years, Drug Interactions:
250-500 mg at the first sign of attack, Monitor closely with:
repeated every 4-6 hours if necessary Alcohol – increased risk of hepatotoxicity with
(maximum, 4 doses in 24 hours). excessive alcohol use (≥3 drinks/day)
Caffeine – increased analgesic efficacy with
NOTE: Infants <3 months should not be given concomitant administration of caffeine.
paracetamol unless advised by a doctor; Chloramphenicol – paracetamol increases
a dose of 10 mg/kg (5 mg/kg if serum concentration levels of
jaundiced) is suitable. chloramphenicol.
Isoniazid – this enhances adverse effects of
Dose Adjustments: paracetamol.
Renal Impairment: Metoclopramide – this increases paracetamol
Longer dosing intervals and reduced total dose absorption.
may be warranted in renal impairment. Sulfonylureas – enhanced hypoglycemic effect
Avoid prolonged or repeated use. of sulfonylureas.
Anticoagulants (e.g., warfarin) – prolonged
Hepatic Impairment: regular use of paracetamol may
Use with caution and avoid prolonged or enhance their anticoagulant effect
repeated use in any type of liver disease. (increased INR and the risk of bleeding).
Contraindicated in severe active liver Avoid concomitant use with:
disease. Activated charcoal, anticholinergics and
Precautions: narcotics – their absorption is decreased
when given concomitantly with
WARNING: Massive overdose may cause paracetamol.
hepatic necrosis and, less frequently, Vaccines – these diminish the therapeutic
renal damage. Lesser overdoses can effect of paracetamol.
frequently cause reversible jaundice.
Administration: May be taken with or without
Sodium restriction (soluble paracetamol food.
products may contain large amounts of
sodium); phenylketonuria (soluble Pregnancy Category: B
products of paracetamol may contain
aspartame); alcohol dependence; ATC Code: N02BE01
overdosage; G6PD deficiency; hepatic

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NERVOUS SYSTEM
A NTI-EPILEPTICS
CARBAMAZEPINE
Rx
Oral: 200 mg tablet (immediate-release
tablet)
200 mg, and 400 mg MR (modified-
release) tablet
100 mg in 5 mL syrup, 120 ml
It is an iminostilbene that limits the firing of
action potentials evoked by a sustained
depolarization in cortical neurons by
slowing the rate of recovery of voltage-
activated Na+ channels from
inactivation.
Indications: Seizures, focal onset with or
without impaired awareness, or the
generalized onset with motor features
(tonic, clonic). Carbamazepine is usually
not effective in absence seizures (petit
mal) and myoclonic seizures (see
Precautions).
For other indications of carbamazepine: see
under Other Psycholeptic Agents and
Neuropathic Pains.
Contraindications: Hypersensitivity to
carbamazepine or related drugs (e.g.
tricyclic antidepressants), or any
component of the formulation;
atrioventricular block; bone marrow
depression; acute intermittent
porphyria; combination with
monoamine-oxidase inhibitors (MAOIs) –
before administering carbamazepine,
MAOIs should be discontinued for 2
weeks or longer (see Drug Interactions).
Dose:
NOTE: As a result of slow, controlled release of
the active substance from the MR
tablets, these are designed to be taken
in a twice-daily dosage regimen.
Epilepsy, by mouth, ADULT, initially 100-200
mg once or twice daily; slowly raise until
an optimal response is obtained
(generally at 400 mg twice or thrice
daily). CHILD, < 5 years, initial 5
mg/kg/day in 2-4 divided doses,
increase every 5-7 days by 5 mg/kg
based on response; 6-12 years, initial 10
mg/kg/day in 2-4 divided doses,
increase by 5 mg/kg/day weekly until
therapeutic levels; > 12 years, 5-10
mg/kg/day divided every 12 hours then
increase gradually to maintenance of
10-30 mg/kg/day divided every 8 or 6
hours (maximum, 1 g/day for 12-15
years old and 1.2 g/day if > 16 years
old).
Dose Adjustments:
Hepatic Impairment:
Metabolism is impaired in advanced liver
disease.
(drug is primarily metabolized in the liver).
Renal Impairment:
Use with caution; dose reduction in moderate
to severe impairment.
Elderly:
Dosage should be selected with caution.
Generally, lower dosages are started.
Precautions:
WARNING:
Hematologic: Agranulocytosis and aplastic
anemia have been reported (see below).
Neurologic: Must be used with caution in
patients with mixed seizures, including
absences, which can be exacerbated by
carbamazepine. In case of exacerbation,
the drug must be discontinued.
Transient or persistent decreased platelet or
white blood cell count can occur.
Agranulocytosis and aplastic anemia
have been associated but the overall risk
estimate is low. Obtain pre-treatment
Complete Blood Counts with platelet
counts at baseline and periodically
thereafter. Discontinue if there is
significant bone marrow depression.
If signs and symptoms of severe skin reaction
appear, carbamazepine should be
discontinued.
Baseline and periodic evaluations of hepatic
function must be performed particularly
in those with a history of liver disease
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NERVOUS SYSTEM
and the elderly. The drug must be
withdrawn immediately in cases of
aggravated liver dysfunction or active
liver disease.
The possibility of activation of latent psychosis
and, in the elderly, confusion and
agitation should be kept in mind.
Breakthrough bleeding may be seen in women
taking oral contraceptives. The reliability
of oral contraceptives may be adversely
affected by carbamazepine. Thus,
women of childbearing age must be
advised to use alternative forms of birth
control.
Pregnancy! the possibility that carbamazepine,
like all major antiepileptic drugs,
increases risk for developmental
disorders has been reported, with rare
reports of developmental disorders,
including spina bifida, with
carbamazepine. Antiepileptic drugs can
aggravate folic acid deficiency so that
supplementation is recommended
before and during pregnancy. Vitamin
K1, to be given to the mother during the
last weeks of pregnancy as well as to the
newborn to prevent bleeding disorders in
the offspring has been recommended.
Lactation: carbamazepine passes into breast
milk so that infants must be closely
observed for adverse reactions.
SKILLED TASKS. Ability to react may be
impaired by dizziness and drowsiness
especially at the start of therapy or
during dose adjustments; patients must
exercise caution when driving or
operating machinery.
Adverse Drug Reactions:
NOTE: Particularly at the start of treatment, or
if the initial dose is too high, or in the
elderly, certain adverse reactions (e.g.,
central nervous system, and
gastrointestinal symptoms, and allergy)
commonly occur.
Common: Neurologic: ataxia, dizziness,
drowsiness, fatigue, headache diplopia,
blurred vision; Skin: allergic reactions,
urticarial (may be severe); Blood:
leucopenia, thrombocytopenia, eosino-
philia; Liver: elevated gamma-GT
(usually not clinically relevant); elevated
Page | 250
alkaline phosphatase; Gastrointestinal:
nausea, vomiting, mouth dryness;
Endocrine/metabolism: edema, weight
increase, hyponatremia and reduced
plasma osmolality.
Less Common: Abnormal involuntary
movements, exfoliative dermatitis,
erythroderma, elevated transaminases,
diarrhea, constipation.
Rare: Orofacial dyskinesia, oculomotor
disorders, slurred speech, peripheral
neuritis, paresthesia, muscle weakness,
hallucinations, depression, loss of
appetite, restlessness, agitation,
confusion, lupus-erythematosus like
syndrome, pruritus, Stevens-Johnson
syndrome, acne, purpura, leukocytosis,
lymphadenopathy, folic acid deficiency,
delayed multiorgan hypersensitivity,
hypertension or hypotension,
disturbance in cardiac conduction.
Very Rare (<0.01%): Agranulocytosis, aplastic
anemia, pure red cell aplasia,
megaloblastic anemia, pancreatitis,
anaphylactic reactions, arrhythmias,
renal or urinary dysfunction.
Drug Interactions:
Monitor closely with:
Co-administration of inhibitors or inducers of
CYP 3A4, the main enzyme catalyzing
conversion of carbamazepine into the
10,11-epoxide (which is as
pharmacologically active as the parent
compound) may result in altered plasma
concentrations of carbamazepine and
either induce adverse reactions or
decrease carbamazepine plasma levels.
Agents that raise carbamazepine plasma
levels: isoniazid, diltiazem, fluoxetine,
macrolide antibiotics (e.g., erythromycin,
clarithromycin), azoles (e.g.,
fluconazole), loratadine, verapamil.
Agents that decrease carbamazepine plasma
levels: phenobarbitone, phenytoin,
theophylline, rifampicin, and possibly,
also clonazepam and valproic acid.
Clonazepam, valproic acid, alprazolam,
corticosteroids, digoxin, doxycycline,
felodipine, haloperidol, theophylline, oral
anticoagulants (warfarin), tricyclic anti-
NERVOUS SYSTEM
depressants- plasma levels can be
lowered by carbamazepine.
Phenytoin- plasma levels of phenytoin can both
be raised or lowered by carbamazepine.
Paracetamol- combination with
carbamazepine may reduce
bioavailability of
paracetamol/acetaminophen.
Isoniazid- combination with carbamazepine
increases isoniazid-induced
hepatotoxicity.
Neuroleptics (e.g., haloperidol) – combination
with carbamazepine can increase
neurological adverse reactions even in
the presence of plasma therapeutic
level.
Diuretics (e.g., hydrochlorothiazide,
furosemide) – these may cause
symptomatic hyponatremia.
Valproic acid may, on the other hand, increase
levels of the active 10,11-epoxide
metabolite so dose adjustments have to
be made.
Avoid concomitant use with:
Monoamine-oxidase inhibitors (MAOIs) –
because they are structurally related to
tricyclic antidepressants,
carbamazepine is not recommended in
combination with MAOIs.
Oral contraceptives – their plasma levels can
be lowered, or their activity diminished
by carbamazepine (alternate
contraceptive methods must be
considered).
Administration: The tablets and the syrup (to
be shaken before use) may be taken
during, after, or between meals. Tablets
should be taken with little liquid. The CR
tablets should be swallowed unchewed
with a little liquid.
Pregnancy Category: D
ATC Code: N03AFA01
VALPROIC ACID/
Rx VALPROATE
Oral: 200 mg/5 ml syrup valproic acid, 100
mL
250 mg and 500 mg divalproex sodium
tablet (sodium valproate and valproic
acid compound in a 1:1 molar
relationship) (immediate-release)
250 mg and 500 mg divalproex sodium
extended release (ER) tablet
500 mg (333 mg sodium valproate +
145 mg valproic acid) controlled
release tablet
Valproate inhibits sustained repetitive firing of
cortical neurons by prolonging recovery
of voltage-activated Na+ channels from
inactivation.
Indications: All forms of seizures, e.g., focal
onset seizures with or without impaired
awareness, multiple seizures types,
generalized seizures with motor (tonic,
clonic, myoclonic, atonic) and non-motor
features (including absence seizures)
and specific syndromes (West, Lennox
Gastaut). Manic episodes associated
with bipolar disorder (see under Other
Psycholeptic Agents).
Contraindications: Known hypersensitivity to
valproic acid or any component of the
formulation; hepatic disease or
significant hepatic dysfunction; urea
cycle disorders; hereditary
neurometabolic syndromes caused by
DNA mutations of the mitochondrial DNA
polymerase-gamma (POLG) gene (e.g.,
Alpers Huttenlocher Syndrome); active
pancreatitis.
Dose:
Epilepsy, by mouth, initiate at 10-15
mg/kg/day, gradually increase by 5-10
mg/kg/week to achieve optimal clinical
response (usual maintenance dose is
20-30 mg/kg/day). Dose above 60
mg/kg/day is not recommended.
For ADULT and CHILD >12 years,
maximum dose is 2.5 grams daily in
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NERVOUS SYSTEM
divided doses; CHILD <12 years and
>20 kg, maximum dose of 35 mg/kg
daily.
In patients previously receiving valproic acid
therapy, divalproex sodium is initiated at
the same daily dose and dosing
schedule.
Mania: see under Anti-Psychosis medicines.
Dose Adjustments:
Renal Impairment:
No adjustment necessary; protein-binding is
reduced.
Hepatic Impairment:
Avoid if possible, hepatotoxicity and hepatic
failure may occasionally occur, usually in
the first six months; avoid in active liver
disease.
Elderly:
Lower initial dose and slower increase in
dosage, regularly monitor fluid and
nutritional intake and increased
somnolence and other side effects.
Precautions:
WARNING:
Hepatic failure resulting in fatalities has
occurred, usually during the first six
months of treatment. Increased risk for
fatal hepatotoxicity is seen in: children <2
years old, patients on multiple
anticonvulsants, congenital metabolic
disorders, severe seizure disorders
accompanied by mental retardation, or
organic brain disease, hereditary
neurometabolic syndromes (see
Contraindications). Patients and
caregivers must be instructed to monitor
for and immediately report non-specific
symptoms such as malaise, weakness,
lethargy, facial edema, anorexia, and
vomiting that may precede the
hepatotoxicity. Loss of seizure control may
also be seen. The drug must be
discontinued immediately in the presence
of suspected or apparent significant
hepatic dysfunction.
Pancreatitis, which may be life-threatening, has
been reported. Some were hemorrhagic
and progressed rapidly from initial
symptoms to death. Patients and
caregivers must be instructed to monitor
Page | 252
for and immediately report symptoms of
abdominal pain, nausea, vomiting, and/or
anorexia. The drug should immediately be
discontinued.
Teratogenicity: may cause neural tube defects.
Do not use in women of child-bearing age
unless the drug is essential.
Hepatotoxicity: see Contraindications and
Warning; Liver function tests (e.g.,
SGPT/ALT, prothrombin time) must be
done pre-treatment and periodically
especially within the first six months and
in patients most at risk.
Pancreatitis: see Warning; measure plasma
amylase immediately if with abdominal
pain.
Thrombocytopenia: Platelet counts and
coagulation tests, should be done before
treatment and periodically thereafter
particularly during the first six months of
therapy, and prior to surgery or
anticoagulant therapy. Thrombocytopenia
may be dose-related. Evidence of
hemorrhage, bruising, or disordered
coagulation are indications for
discontinuation.
Pregnancy! Valproic acid may cause teratogenic
effects, such as neural tube defects (e.g.,
spina bifida). It must be considered in
women of child-bearing age only after the
risks have been carefully weighed against
the benefits. Pregnant women on valproic
acid must be immediately referred to the
specialist.
Urea cycle disorders: see Contraindications.
Hyperammonemic encephalopathy,
some- times fatal, has been reported in
patients with these disorders.
An increase in the risk of suicidal thoughts and
behavior in patients taking antiepileptic
drugs (AEDs) has been reported.
Epilepsy and other illnesses for which
AEDs are prescribed can carry the same
risk. Patients and their caregivers must
be instructed to monitor for and
immediately report any unusual change
in mood or behavior.
Pediatric Use: Children less than 2 years of age
are at increased risk for fatal
hepatotoxicity (see Warning). When used
NERVOUS SYSTEM
in this age group, it should be done with
extreme caution and as a sole agent.
SKILLED TASKS: ability to react may be
impaired by dizziness and drowsiness
especially at the start of therapy or
during dose adjustments; patients must
exercise caution when driving or
operating machinery.
Adverse Drug Reactions:
NOTE: The frequency of adverse effects,
particularly elevated liver enzymes and
thrombocytopenia, can be dose-related.
Common:
Gastrointestinal: Nausea, vomiting, abdominal
pain, diarrhea, anorexia, dyspepsia,
elevated AST/ALT (usually minor and
appear to be dose-related).
Neurologic: Somnolence, tremor, dizziness,
insomnia, nervousness, anxiety,
depression, amnesia, mood changes,
hallucinations, nystagmus, blurred
vision, amblyopia, ataxia, vertigo.
Hematologic: Thrombocytopenia, increased
bleeding time, petechiae/ecchymosis.
Respiratory: Flu syndrome, infection,
bronchitis, rhinitis, pharyngitis.
Others: Asthenia, headache, transient
alopecia, skin rash, increased appetite,
weight gain, tinnitus.
Less Common: Irregular menses, secondary
amenorrhea.
Rare: Hepatic failure (may be fatal),
pancreatitis, hyperammonemia,
Stevens-Johnson syndrome, toxic
epidermal necrolysis (see Warning and
Precautions).
Drug Interactions:
Monitor closely with:
Aspirin – this increase valproate free fraction
levels by plasma protein binding
competition.
Amitriptyline/Nortriptyline – its plasma
clearance is decreased with co-
administration of valproate. Consider
lowering dose of
amitriptyline/nortriptyline.
Carbamazepine – valproate may increase or
decrease carbamazepine levels.
Diazepam – valproate displaces diazepam
from binding sites and inhibits its
metabolism, increasing free fraction of
diazepam.
Phenobarbital – valproate inhibits its
metabolism; closely monitor for
neurologic toxicity, including CNS
depression.
Phenytoin – valproate displaces phenytoin
from binding sites and inhibits its
metabolism, increasing free fraction of
phenytoin.
Rifampin – increases oral clearance of
valproate; with need to adjust valproate
dosage.
Warfarin – in an in vitro study, valproate
increased unbound fraction of warfarin.
Its therapeutic relevance is unknown;
however, coagulation tests should be
monitored.
Avoid concomitant use with:
Carbapenem antibiotics (e.g., meropenem,
imipenem, ertapenem) – these decrease
valproate levels; can result in loss of
seizure control (alternative antibacterial
or anticonvulsant therapy should be
considered).
Administration:
Swallow tablets whole, do not chew or crush.
Taken preferably after food intake. If
dose is skipped, do not double the next
dose.
Pregnancy Category: D
ATC Code: N03AG01
DIAZEPAM
Rx
Inj.: 5 mg/mL, 2 mL ampul (IV)
Intravenous diazepam is a benzodiazepine
used in the management of seizure
activity and for anxiolysis with close
neurovital signs monitoring in severely
agitated patients.
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NERVOUS SYSTEM
Indications: Initial and immediate suppression
of convulsive and non-convulsive status
epilepticus prior to transfer to hospital;
recurrent or prolonged febrile
convulsions; recurrent generalized or
grand mal seizures associated with
poisoning and drug and acute alcohol
withdrawal.
IMPORTANT NOTE: Patients in status
epilepticus and those with generalized
tonic and/or clonic convulsions must be
immediately brought to the nearest
hospital.
Contraindications: Known hypersensitivity to
diazepam or any of the excipients;
respiratory depression; marked
neuromuscular respiratory weakness,
including unstable myasthenia gravis;
acute pulmonary insufficiency; sleep
apnea syndrome; phobic or obsessional
states; hyperkinesis; severe hepatic
impairment;
Dose: (See Precautions prior to
administration).
Status epilepticus (convulsive and non-
convulsive), by very slow IV injection,
ADULT and CHILD >12 years, 5-10 mg at
a rate not exceeding 2 mg/minute,
repeated as necessary every 5-10
minutes until seizures stop or up to a
maximum total dose of 20 mg; INFANT
>1 month and CHILD up to 12 years,
300-400 micrograms/kg at a rate not
exceeding 1 mg/minute every 15-30
minutes up to a maximum total dose of
5 mg in infants, and 10 mg for older
children (monitor closely for respiratory
depression, coma and hypotension).
Prolonged or recurrent febrile convulsions, by
slow IV injection, INFANT and CHILD, use
same dose for status epilepticus
(monitor closely for respiratory
depression, coma and hypotension).
Seizures associated with poisoning, by slow IV
injection (at a rate not exceeding 2
mg/minute), ADULT, 100-150
micrograms/kg (monitor closely for
respiratory depression, coma and
hypotension).
Page | 254
IMPORTANT PRECAUTION! Monitor closely for
respiratory depression, coma and
hypotension when giving IV diazepam.
Dose Adjustments:
Elderly or Debilitated Patients:
Reduce dose.
Renal Impairment:
No dose adjustment recommended unless
used for prolonged periods; reduce dose
in prolonged periods.
Hepatic Impairment:
Reduce maintenance dose. Contraindicated in
severe liver disease.
Precautions:
WARNING: Overdose may produce coma and
respiratory depression.
When diazepam is given intravenously, agents
for correcting hypotension and facilities
for supporting ventilation (e.g., AMBU
bag, oxygen) in cases of respiratory
depression should be available. In such
cases, the patient should be referred to
the nearest hospital immediately.
Hepatic impairment and renal impairment (can
precipitate coma in cases of severe
hepatic and renal impairment); avoid
prolonged use and abrupt withdrawal.
Respiratory disease (compromised respiratory
drive in respiratory disease or sleep
apnea may lead to hypoventilation and
hypoxemia); muscle weakness may
worsen; history of alcohol or drug abuse,
marked personality disorder; use only if
the indication is clear, such as seizure
control; porphyria.
Pregnancy (high doses during late pregnancy
or labor may cause neonatal
hypothermia, hypotonia, and respiratory
depression); breastfeeding (adverse
effects are possible; monitor infant for
drowsiness);
Adverse Drug Reactions:
Common: Intravenous: Coma or sensorial
depression, hypotension, respiratory
depression.
NERVOUS SYSTEM
Rare: Allergic reactions, including anaphylaxis;
jaundice, transient elevated liver
function tests.
Drug Interactions:
Monitor closely with:
Amlodipine – enhanced hypotensive effect.
Azole derivatives (e.g., fluconazole) – these
may inhibit diazepam’s metabolism,
increasing the risk of adverse effects.
Chlorphenamine – enhanced sedative effect.
Chlorpromazine – enhanced sedative effect.
CNS depressants (e.g., alcohol, sedatives and
tranquilizers) – possibly enhanced CNS
depression and sedative effect.
Enalapril – enhanced hypotensive effect.
Furosemide – enhanced hypotensive effect.
Hydrochlorothiazide – enhanced hypotensive
effect.
Methyldopa – enhanced hypotensive effect.
Nitrates (e.g., isosorbide dinitrate) – enhanced
hypotensive effect.
Phenytoin – diazepam may possibly increase
or decrease the concentration of this
drug.
Seizure-inducing drugs (see Appendix – Table
C for other drugs which may also cause
seizures) – these may lower seizure
threshold when given concomitantly with
benzodiazepines.
Theophylline – these may reduce sedative
effects of benzodiazepines.
Avoid concomitant use with:
Isoniazid – metabolism of diazepam inhibited.
Rifampicin – this may substantially accelerate
metabolism of diazepam, thus reducing
its concentration and clinical effect.
Administration: Give IV at a slow rate not faster
than 2 mg/minute.
NOTE: Avoid extravasation, intra-arterial and
IM injection. Avoid dilution and infusion
of injection, as diazepam has a low
solubility and adsorbs to PVC-giving sets.
Pregnancy Category: D
ATC Code: N05BA01
FOR ECLAMPSIA
MAGNESIUM SULFATE
Rx
Inj.: 250 mg/mL, 2 mL and 10 mL ampul and
20 mL vial (IM, IV)
500 mg/mL, 2 mL and 10 mL ampul (IM,
IV)
A sterile preparation that contains magnesium
as heptahydrate.
Indications: The drug of choice for the
prevention of seizures in women with
severe pre-eclampsia, and for controlling
seizures or preventing their recurrence
among eclamptic patients (see also
Chapter __ Genitourinary System and
Sex Hormones).
Contraindications: Known hypersensitivity to
magnesium and its salts; heart block;
myocardial infarction;
hypermagnesemia; deranged renal
function; myasthenia gravis.
Dose:
Control of seizures and prevention of recurrent
seizures in eclamptic patients, IV loading
dose of 4 g over 5-15 minutes followed
by maintenance IV infusion of 1 g/hour
for at least 24 hours after the last
seizure or delivery (whichever occurs
later), or by deep IM injection (used for
special situations; when IV lines are not
available), 5 g into each buttock, then 5
g every 4 hours into alternate buttocks
for at least 24 hours after the last
seizure or delivery (recurrent seizure
should be treated by further IV bolus of 2
g; 4 g if body weight is over 70 kg).
DILUTION AND ADMINISTRATION. According to
manufacturer’s directions. The
concentration of magnesium sulfate
should not exceed 20% (dilute 1 part of
magnesium sulfate injection, 50%, with
at least 1.5 parts of water for injection);
for IM injection, mix magnesium sulfate
Page | 255
NERVOUS SYSTEM
injection, 50%, with 1 mL lidocaine
injection, 2%.
Dose Adjustment:
Renal Impairment:
Dose should not exceed 20 g/48 hours (use
with caution).
Precautions:
WARNING: Magnesium toxicity causes loss of
deep tendon reflexes, followed by
respiratory depression and ultimately
respiratory arrest. In most cases,
therapy can be monitored safely by
hourly measurement of the patellar
reflex and respiratory rate (or oxygen
saturation). If deep tendon reflexes are
absent, further doses of magnesium
sulfate should be withheld until reflexes
return.
Magnesium can be reversed with
calcium gluconate. Calcium is
administered as a 10-20 mL IV of 10%
solution, and can be given as an antidote
for problematic signs associated with
hypermagnesemia.
NOTE: Magnesium is excreted by the
kidney and regular monitoring of serum
levels should be considered in women
with oliguria (urine output <100 mL/4
hours). If repeated seizures occur
despite magnesium, other pre-hospital
options include administering diazepam.
Myasthenia gravis (since Mg interferes with
neuromuscular transmission; possible
marked increase in weakness,
particularly of respiratory musculature);
hepatic impairment (avoid in hepatic
coma if there is risk of renal failure);
renal impairment (increased risk of
toxicity, e.g., hypermagnesemia).
Pregnancy (third trimester: not known to be
harmful for short-term IV administration
in eclampsia, but excessive doses may
cause neonatal respiratory depression).
Adverse Drug Reactions:
Common: Flushing, nausea, vomiting.
Less Common: Dizziness, drowsiness,
headache, thirst.
Page | 256
Rare: Arrhythmias, cardiac arrest, coma,
confusion, loss of tendon reflexes,
muscle weakness, respiratory
depression.
Drug Interactions:
Monitor closely with:
Aminoglycosides – there is additive
neuromuscular blocking effect.
CNS depressants (e.g., barbiturates, opiates or
general anesthetics) – additive central
depressant effects.
Neuromuscular blockers (e.g., tubocurarine,
vecuronium and succinylcholine) –
potentiation of neuromuscular blockade.
Nifedipine – this increases effects of
parenteral magnesium sulfate and risk
of hypotension.
Administration: For IV administration, the rate
of injection should not exceed 150
mg/minute.
Pregnancy Category: D
ATC Code: Not available
ANTI-PARKINSON DRUGS
BIPERIDEN
Rx
Oral: 2 mg tablet (as hydrochloride)
A tertiary-amine, centrally-acting
anticholinergic drug, used in the
management of Parkinsonism and is
effective for the treatment of acute EPS.
Indications: Drug-induced extrapyramidal
symptoms (except tardive dyskinesia) by
phenothiazines, butyrophenones or
reserpine; adjunctive treatment of post-
encephalitic, idiopathic or
arteriosclerotic Parkinson’s disease.
Contraindications: Hypersensitivity to
biperiden or any component of the
formulation; angle-closure glaucoma;
NERVOUS SYSTEM
untreated urinary retention; prostatic Adverse Drug Reactions:
hypertrophy; myasthenia gravis; and GI Common: Blurred vision, confusion,
obstruction or atony; toxic megacolon. constipation, decreased sweating,
disorientation, dizziness, drowsiness,
Dose: dryness of mouth, flushing,
Parkinsonism, by mouth, ADULT, 2 mg every 8 lightheadedness, mydriasis, nausea,
or 6 hours, with initial dose of 0.5- nervousness, reduced bronchial
1mg/day, gradually increase by 0.5 mg secretions, thirst, urinary hesitancy and
every 5-6 days until optimum dose. retention, vomiting.
Drug-induced extrapyramidal disorders, by Less Common or Rare: Agitation, angle-closure
mouth, ADULT, 1-4 mg/day, in single or glaucoma, arrhythmias, delirium,
2 divided doses; CHILD > 3 years, 0.02- delusions, diplopia, epigastric distress,
0.05 mg/kg/dose every 8-12 hours. excitement, hallucinations, hypotension,
memory impairment, muscular cramping
Dose Adjustments: and weakness, palpitations, paralytic
Elderly: ileus, paresthesia, psychiatric
Start with low dose and increase slowly to the disturbances, rash, bradycardia followed
lowest effective dose. by tachycardia, urticaria.

Hepatic Impairment: Drug Interactions:

For mild-to-moderate hepatic impairment,
dose reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
Avoid abrupt withdrawal in Parkinson’s disease
(to prevent acute exacerbation); may
exacerbate tardive dyskinesia caused by
antipsychotic drugs; heart diseases,
including arrhythmias, coronary heart
disease, and heart failure (may be
exacerbated); inflammatory bowel
disease (risk of paralytic ileus);
dementia (anticholinergics are best
avoided; they may worsen symptoms
and antagonize therapeutic effects of
anticholinesterases); fever or high
ambient temperature (risk of
hyperthermia); GERD (may be
aggravated); the elderly (more sensitive
to anticholinergic adverse effects;
confusion may be precipitated or
worsened); children (more susceptible to
anticholinergic side-effects); hepatic
impairment.
Pregnancy and breastfeeding (use with
caution).
SKILLED TASKS. May impair ability to perform
skilled tasks, e.g., machinery or driving.
NOTE: Concomitant use of two or more drugs
having antimuscarinic effects can
increase side-effects, such as
constipation, urine retention and
dryness of mouth, and can also lead to
confusion especially in the elderly.
Monitor closely with:
Antipsychotic drugs (e.g., phenothiazines,
haloperidol) – possible masking of
extrapyramidal symptoms, tardive
dyskinesia, in long-term therapy with
these drugs.
Fluphenazine – increased antimuscarinic
effects (but reduced plasma
concentration of fluphenazine).
Isosorbide Dinitrate – possibly reduced effect
of the sublingual ISDN (failure to
dissolve under the tongue owing to dry
mouth).
Avoid concomitant use with:
Alcohol – potentiates CNS depression.
Anticholinergic drugs or other drugs with
anticholinergic effects (see Appendix –
Table A) – these increase the risk of
adverse effects (including central
anticholinergic delirium, which is often
missed); avoid these combinations if
possible (if a combination is required,
monitor the patient, and reduce its dose
if necessary).

Page | 257
NERVOUS SYSTEM
Anticholinesterases (e.g., neostigmine and
pyridostigmine) and cisapride –
combining anticholinergics with these
drugs, which increase concentration of
acetylcholine, will antagonize the
anticholinergic effect.
Haloperidol – its therapeutic effects may be
reduced by biperiden (due to central
antagonism).
Levodopa – its absorption is possibly reduced
by biperiden.
Metoclopramide – its effects on GI activity is
antagonized by biperiden.
Administration: The tablet should be taken with
food.
Pregnancy Category: C
ATC Code: N04AA02
LEVODOPA + CARBIDOPA
Rx
Oral: 100 mg levodopa + 25 mg carbidopa per
tablet, immediate release
250 mg levodopa + 25 mg carbidopa per
tablet, immediate release
200 mg levodopa + 50 mg carbidopa per
extended release tablet
Levodopa is an aromatic amino acid and the
naturally-occurring form of dihydroxy-
phenylalanine. It is the immediate precursor
to dopamine and can pass through the
blood-brain barrier, where it is immediately
taken up by dopaminergic neurons and
converted into dopamine. It is administered
with carbidopa, a peripheral decarboxylase
inhibitor that prevents gut metabolism of
levodopa, thereby increasing dopamine in
the CNS.
Indication: Management of Parkinson’s
disease, including idiopathic parkinsonism,
Page | 258
post-encephalitic parkinsonism, and
symptomatic parkinsonism.
Contraindications: Narrow angle glaucoma;
history of melanoma.
Dose:
Parkinson’s disease, by mouth, ADULT,
Immediate-release, initially 100mg/25 mg
2 to 3 x per day, may be increased gradually
by 100 mg/25 mg every other day
(maximum, 800 mg/200 mg daily in divided
doses);
Extended-release, initially 200 mg/50 mg
once or twice a day, may be increased
gradually by 100 mg/25 mg to 200 mg/50
mg every other day (maximum, 2,450
mg/612.5 mg daily in divided doses).
Precautions:
Abnormal thinking or behavioral changes e.g.
aggressive behavior, agitation, confusion,
delirium, disorientation, delusion, paranoid
ideation and psychotic like behavior;
hallucinations (typically presents shortly
after initiation of therapy; may require dose
reduction); psychotic disorders (use with
extreme caution; at risk of exacerbating
psychosis; depression with concomitant
suicidal tendencies).
Dyskinesias (may require dosage reduction);
impulse control disorders.
Leukopenia; melanoma (monitor closely;
perform periodic skin examinations).
Neuroleptic malignant syndrome (rapid dose
reduction, or abrupt withdrawal; monitor
closely for this reaction; discontinue
immediately if signs and symptoms arise);
peripheral neuropathy.
Cardiovascular disease (use with caution);
orthostatic hypotension (monitor closely for
signs and symptoms of postural
hypotension, especially during dose
escalation).
Somnolence (evaluate for factors that may
increase these risks such as concomitant
sedating medications, and the presence of
sleep disorders; monitor for drowsiness or
sleepiness).
NERVOUS SYSTEM
Endocrine disease (use with caution in patients
with endocrine disease and when
interpreting plasma or urine catecholamine
levels; falsely diagnosed
pheochromocytoma).
Glaucoma (use with caution; monitor IOP
carefully); respiratory disease.
Peptic ulcer disease (use with caution); hepatic
and renal impairment.
Elderly (use with caution; may be more
sensitive to CNS effects, e.g.,
hallucinations).
Pregnancy (safety has not been established);
lactation (can cause reduced serum
prolactin levels, resulting in reversible
suppression of lactation).
SKILLED TASKS. May impair ability to perform
tasks, which require mental alertness, like
driving or operating machinery.
Adverse Drug Reactions:
Common: Abnormal dreams, anorexia, anxiety,
arrhythmias, chorea, confusion, dementia,
depression, dizziness, drowsiness, dry
mouth, dyskinesia, dystonia, euphoria,
fatigue, insomnia, nausea, palpitations,
postural hypotension, psychosis, syncope,
taste disturbances, vomiting.
Less Common: Ataxia, chest pain,
constipation, diarrhea, dysphagia,
flatulence, hand tremor, hoarseness,
hypersalivation, hypertension, malaise,
muscle cramps, edema, reddish
discoloration of the urine and other body
fluids, weakness, weight changes.
Rare: Abdominal pain, activation of malignant
melanoma, agitation, alopecia, blurred
vision.
Drug Interactions:
Monitor closely with:
Blood Pressure Lowering Agents: with
enhanced therapeutic effect (hypotensive
effect)
TCAs: Increases absorption of Levodopa +
Carbidopa
Antacids, Anticholinergics, TCAs e.g.,
Amytriptylline: Increases bioavailability of
Levodopa + Carbidopa:
Biperiden (choreic movements or dyskinesias),
Methylphenidate, Papaverine (hypotensive
effect): Increases risk of adverse or toxic
effects of Levodopa + Carbidopa
Drugs whose risk of adverse or toxic effects is
increased by levodopa:
Antihypertensives (orthostatic hypotension)
Bupropion
Duloxetine (hypotensive effect)
MAOIs (hypertensive reactions)
Selegiline (severe orthostatic hypotension)
Drugs that reduce therapeutic effect of
Levodopa + Carbidopa:
Benzodiazepines, Dopamine Receptor
Antagonists, Isoniazid, Methionine [with
large doses], Metoclopramide,
Multivitamins / Fluoride with ADE
[pyridoxine when used in the absence of a
dopa decarboxylase inhibitor],
Multivitamins / Minerals e.g., ADEK, Folate,
Iron, (Oral), Multivitamins / Minerals with
AE, no Iron [pyridoxine when used in the
absence of a dopa decarboxylase inhibitor],
Papaverine, Phenytoin, Pyridoxine
Antipsychotics: therapeutic effects can be
reduced by levodopa
Avoid concomitant use with:
Non-selective MAOIs: Adverse or toxic effects
(hypertensive crisis) can be increased by
Levodopa
Administration: Should be taken on an empty
stomach.
Pregnancy Category: C
ATC Code: N04BA02
Page | 259
NERVOUS SYSTEM
OTHER DRUGS FOR PARKINSONISM
DIPHENHYDRAMINE
Rx
Oral: 25 mg and 50 mg capsule (as
hydrochloride)
Inj.: 50 mg/mL, 1 mL ampul (IM, IV) (as
hydrochloride)
A monoethanolamine-derived, first-generation
H1 receptor antagonist, which exhibits
antimuscarinic and pronounced
sedative property, with low incidence of
GI side effects.
Indication: Drug-induced dystonic reaction
(Extrapyramidal Syndrome).
Contraindications: See under Anti-histamines.
Dose:
Drug-induced dystonic reaction
(extrapyramidal syndrome), by IM or IV
injection, ADULT, 25-50 mg in a single
dose, may repeat in 20-30 minutes if
necessary; CHILD, 0.5-1 mg/kg/dose.
See under Anti-Histamines for other dose
adjustments, precautions, adverse drug
reactions and other therapeutic
information.
LOCAL ANESTHETIC
LIDOCAINE
Rx
Inj.: 1%, 20 mL ampul (local infiltration) (as
hydrochloride)
2%, 5 mL and 50 mL vial (local
infiltration) (as hydrochloride)
2%, 1.8 mL carpule (with epinephrine)
(local infiltration)
Topical: 10% (as hydrochloride) spray, 50 mL
A moderately long-acting, local anesthetic,
which blocks initiation and transmission
Page | 260
of nerve impulses at the site of
application by stabilizing neuronal
membrane.
Indications:
Injection: infiltration anesthesia; peripheral
and sympathetic nerve block;
Topical: local (surface) anesthetic for oral
mucous membrane prior to oral and
dental procedures.
Contraindications: Known or suspected
hypersensitivity to lidocaine or any
component of the formulation; adjacent
skin infection or inflamed skin to the
proposed site of injection; concomitant
therapy with anticoagulants or an
abnormal bleeding tendency; severe
anemia or heart disease; spinal/epidural
anesthesia in dehydrated or
hypovolemic patients; hypersensitivity to
another local anesthetic of the amide
type (topical).
Dose:
NOTE: Administer the smallest dose and
concentration required to produce the
desired result.
NOTE: Use lower doses for debilitated or elderly
patients or in epilepsy or acute illness.
Local anesthetic for oral mucous membrane,
topical administration of spray, ADULT,
please see under Lidocaine in the
chapter on Sensory Organs.
Local or percutaneous infiltration and
peripheral nerve block, by SC or ID
injection, ADULT, 5-300 mg.
Peripheral nerve block, CHILD, 505
micrograms/kg.
NOTE: Maximum safe doses of lidocaine
for ADULT and CHILD are: 4 mg/kg for the
1% lidocaine.
Dose Adjustments:
Renal Impairment:
Reduce its dose during prolonged infusion
(>24 hours) or repeated IV doses.
Hepatic Impairment:
Consider halving its dose during prolonged
infusions (>24 hours) or repeated IV
doses.
NERVOUS SYSTEM
Precautions:
Topical:
Application to broken or inflamed skin may
lead to increased systemic absorption;
do not leave on large body areas for >2
hours.
Pregnancy (the amount of lidocaine absorbed
topically varies by dose administered,
duration of exposure, and site of
application; cumulative exposure from
all routes of administration should be
considered).
Injectable:
Severe bradycardia, heart block or impaired
cardiac conduction (local anesthetics
enhance conduction defects); severe
shock; respiratory impairment; renal
impairment; hepatic impairment;
epilepsy; porphyria; neuromuscular
diseases (e.g., myasthenia gravis)
(increases sensitivity to local
anesthetics; may increase muscle
weakness and depress respiration with
central neural blockade); neurological
disease (administration of local
anesthetics may worsen condition); the
elderly (increased sensitivity); children
<6 months (more sensitive to toxic
effects).
Solutions containing epinephrine should be
used with caution for ring block of digits
or appendages to prevent risk of
ischemic necrosis.
The elderly or debilitated patients (should be
given reduced doses commensurate
with their age and physical status).
Pregnancy (large doses should be avoided
during third trimester to diminish risk of
neonatal respiratory depression,
hypotonia and bradycardia after
paracervical block); breastfeeding.
Adverse Drug Reactions:
INJECTABLE
Common: Blurred vision, chest pain, confusion,
disturbances in vision, dizziness,
drowsiness, dyspnea, flushing,
headache, light-headedness, nausea,
paresthesia, tinnitus, tremors.
Less Common: Arrhythmias, bradycardia,
cardiac arrest, coma, heart block,
hypotension, muscle twitching,
recurrence of SVT, respiratory
depression, restlessness, seizures.
Rare: Bronchospasm, convulsions,
hypersensitivity reactions, paraplegia,
unconsciousness.
TOPICAL
Frequency Not Defined:
Application site reactions: abnormal sensation,
altered temperature sensation, burning
sensation, edema, erythema, itching,
pallor or blanching when application
time is prolonged (>2 hours), rash,
redness.
Systemic reactions (unlikely due to small dose
absorbed; may occur with repeated
doses or application to large surface
areas): angioedema, bronchospasm,
cardiovascular manifestations (e.g.,
bradycardia, hypotension), CNS
excitation and/or depression, confusion,
dizziness, double or blurred vision,
drowsiness, euphoria, nervousness,
respiratory depression, shock, tinnitus,
tremors, twitching, unconsciousness,
vomiting.
Drug Interactions:
Monitor closely with:
Beta-blockers – these may increase the serum
concentration of lidocaine (topical),
increasing the risk of toxicity.
Avoid concomitant use with:
Bupivacaine – lidocaine increases toxicity of
bupivacaine, never use combination.
Antiarrhythmics (e.g., amiodarone, sotalol and
disopyramide) – lidocaine has
proarrhythmic effect; combination with
these drugs may cause antagonistic
effect.
Diuretics (e.g., furosemide,
hydrochlorothiazide) – action of
lidocaine is antagonized by hypokalemia
caused by these drugs.
Drugs which depresses cardiac contractility
and conduction – possibly increased risk
of heart failure and significant
bradyarrhythmia.
Page | 261
NERVOUS SYSTEM
Administration: For topical use, apply a
moderately thick layer to affected area
(~1/8 inch thick), and allow time for
numbness to develop (20-60 minutes for
application).
Pregnancy Category: B
ATC Code: N01BB02
DRUGS FOR NEUROPATHIC PAIN
CARBAMAZEPINE
Rx
Oral: 200 mg tablet
200 mg and 400 mg MR (modified-
release) tablet
100 mg in 5 mL syrup, 120 mL
It is an iminostilbene that limits the firing of
action potentials evoked by a sustained
depolarization in cortical neurons
mediated by a slowing of the rate of
recovery of voltage-activated Na+
channels from inactivation.
Indications: Idiopathic trigeminal neuralgia and
painful diabetic neuropathy
Contraindications: Known hypersensitivity to
carbamazepine or structurally related
drugs (e.g. tricyclic antidepressants), or
any component of the formulation;
atrioventricular block; bone marrow
depression; acute intermittent
porphyria; combination with
monoamine-oxidase inhibitors (MAOIs)-
before administering carbamazepine,
MAOIs should be discontinued for 2
weeks or longer (see Drug Interactions).
Dose:
Idiopathic trigeminal neuralgia, by mouth,
ADULT, initial dosage of 100 mg 2 times
daily can be raised gradually until
freedom from pain is achieved (usually
at 200 mg 3-4 times daily); then,
Page | 262
gradually reduce the dose to the lowest
possible maintenance level.
Painful diabetic neuropathy, by mouth, ADULT,
start with 100 mg 1 to 2 times a day,
gradually increase depending on
response; average dose is 200 mg 2-4
times daily.
NOTE: Dizziness and drowsiness may impair
performance of skilled or manual tasks.
Dose Adjustments:
Hepatic Impairment:
Metabolism is impaired in advanced liver
disease.
Renal Impairment:
Use with caution.
Elderly:
Dosage should be selected with caution.
Generally, lower dosages are started.
See under Antiepileptic Medicines for crucial
information about Indications, Warnings
and Precautions, Drug Interactions and
other information.
GABAPENTIN
Rx
Oral 100 mg and 300 mg capsule
Gabapentin selectively binds to α2δ subunits of
voltage-sensitive calcium channels, causing
closure of N and P/Q presynaptic calcium
channels that diminishes excessive
neuronal activity and neurotransmitter
release.
Indication: Management of postherpetic
neuralgia (PHN) in adults; neuropathic pain.
Contraindication: Hypersensitivity to
gabapentin or any component of the
formulation.
Dose:
Postherpetic neuralgia, by mouth, ADULT,
Initiate at 300 mg per day then gradually
increase to 300 mg twice daily; may
NERVOUS SYSTEM
increase to 300 mg 3 times daily or higher.
Titrate dose as needed for pain relief,
usually ranging from 1,800–3,600 mg daily
in divided doses. Watch out for side effects.
Neuropathic pain, by mouth, ADULT, Initiate at
300 mg per day then gradually increase to
300 mg twice daily; may increase to 300 mg
3 times daily or higher. Titrate dose as
needed for pain relief, usually ranging from
1,800–3,600 mg daily in divided doses.
Watch out for side effects.
NOTE: Dizziness and drowsiness may impair
performance of skilled or manual tasks.
Dose Adjustments:
Geriatric:
Dose reductions may be needed based on
renal function.
Renal Impairment:
Adjust doses for renal function.
In CrCl ≥60 mL/minute, administer 300–
1,200 mg 3 times daily.
In CrCl >30 to 59 mL/minute, administer 200–
700 mg twice daily.
In CrCl >15 to 29 mL/minute, administer 200–
700 mg once daily.
In CrCl 15 mL/minute, administer 100–300
mg once daily.
In CrCl <15 mL/minute, reduce daily dose in
proportion to creatinine clearance based on
dose for CrCl 15 mL/minute (e.g., reduce
dose by one-half [range: 50–150 mg daily]
for CrCl 7.5 mL/minute).
In ESRD requiring hemodialysis, adjust dose
based on CrCl plus a single supplemental
dose of 125–350 mg after each 4 hours of
hemodialysis.
Precautions:
Mixed seizures including absences; Acute
pancreatitis (discontinue if acute
pancreatitis develops); Renal impairment;
Hemodialysis; Not recommended for
patients who need to sleep during daytime
and remain awake at night.
Elderly; Children; Pregnancy (crosses the
placenta; adverse events have been
observed in animal reproduction studies);
Lactation (use only if the benefits to the
mother outweigh the potential risk to the
infant).
SKILLED TASKS. May impair ability to perform
tasks, which require mental alertness, like
driving or operating machinery.
Adverse Drug Reactions:
Common: Dizziness, drowsiness, ataxia,
fatigue, hostility, tremor, emotional lability,
hyperkinesia, abnormality in thinking,
headache, abnormal gait, depression,
amnesia, nervousness, hyperesthesia,
lethargy, pain, twitching, vertigo, pruritus,
weight gain, skin rash, hyperglycemia,
diarrhea, nausea and vomiting, xerostomia,
constipation, abdominal pain, dyspepsia,
dry throat, dental disease, flatulence,
increased appetite, urinary tract infection,
impotence, decreased white blood cell
count, leukopenia, infection, weakness,
back pain, dysarthria, myalgia, bone
fracture, limb pain, viral infection,
nystagmus, diplopia, blurred vision,
conjunctivitis, nasopharyngitis, rhinitis,
otitis media, bronchitis, pharyngitis,
respiratory tract infection, cough, fever,
peripheral edema, vasodilatation.
Less Common: Acute renal failure, altered
serum glucose, anemia, angina pectoris,
angioedema, aphasia, aspiration
pneumonia, blindness, blood coagulation
disorder, bradycardia, brain disease, breast
hypertrophy, bronchospasm, cardiac
arrhythmia (various), cerebrovascular
accident, cardiac failure, colitis, confusion,
Cushingoid appearance, CNS neoplasm,
DRESS syndrome, drug abuse, dyspnea,
erythema multiforme, drug dependence,
facial paralysis, fecal incontinence,
gastroenteritis, glaucoma, glycosuria,
hearing loss, hematemesis, hematuria,
hemiplegia, heart block, hemorrhage,
hepatitis, hepatomegaly, herpes zoster,
hyperlipidemia, hypertension,
hyperthyroidism, hyponatremia,
hypotension, hyperventilation,
hypoventilation, hypothyroidism, jaundice,
Page | 263
NERVOUS SYSTEM
leukocytosis, lymphadenopathy, joint concomitantly]; Orphenadrine;
swelling, lymphocytosis, memory Paraldehyde; Thalidomide; Zolpidem (CNS
impairment, meningism, migraine, depressant effect) – Gabapentin may
movement disorder, myocardial infarction, enhance therapeutic effects of these drugs
myoclonus (local), nerve palsy,
nephrolithiasis, nephrosis, non-Hodgkin's TEST INTERACTION. May cause a false positive
lymphoma, palpitations, pancreatitis, result with the Ames N-Multistix SG®
ovarian failure, paresthesia, peptic ulcer, dipstick test for urine protein.
pericardial effusion, pericardial rub,
pericarditis, peripheral vascular disease, Administration: May be taken with or without
pneumonia, psychosis, pulmonary food. Administer first dose on first day at
thromboembolism, retinopathy, purpura, bedtime to avoid somnolence and
rhabdomyolysis, seasonal allergy, skin dizziness. When given 3 times daily, the
necrosis, status epilepticus, Stevens- maximum time between doses should not
Johnson syndrome, subdural hematoma, exceed 12 hours.
suicidal ideation, suicidal tendencies,
syncope, tachycardia, thrombophlebitis, Do NOT discontinue abruptly because of the
tumor growth, thrombocytopenia, possibility of increasing seizure frequency.
withdrawal syndrome. Withdraw gradually to minimize the
potential of increased seizure frequency,
Drug Interactions: unless safety concerns require a more rapid
Monitor closely with: withdrawal.
Brimonidine (Topical); Hydroxyzine;
Minocycline; Nabilone - Enhance CNS Pregnancy Category: C
Depressant effect of Gabapentin
Ethyl alcohol; Mirtazapine (CNS depressant ATC Code: N03AX12
effect); Pramipexole, Ropinirole, Rotigotine
(sedative effect) – Therapeutic effects may
be enhanced by gabapentin. PSYCHOLEPTICS
CNS Depressants [except Levocabastine,
Nasal] - Increases risk of adverse or toxic ANTIPSYCHOTIC MEDICINES
effects of Gabapentin
SSRIs e.g., Fluoxetine – Gabapentin Increases
CHLORPROMAZINE
risk of adverse or toxic effects of (e.g.,
psychomotor impairment)
Rx
Avoid concomitant use with: Oral: 50 mg, 100 mg and 200 mg tablet
Antacids [administer gabapentin at least 2 Inj.: 25 mg/mL, 1 mL ampul (IM, IV) (as
hours after antacid]; Magnesium Salts hydrochloride)
[administer gabapentin at least 2 hours
after magnesium salts]; Mefloquine - NOTE: Only for rural and municipal health units
Decreases serum concentration of with physicians who have undergone
Gabapentin training under the Mental Health
Droperidol; Magnesium salts; Perampanel; Medicines Access Program (MHMAP)
Sodium oxybate - Enhances therapeutic and qualified to prescribe
effect of Gabapentin psychopharmacologic medicines.

Buprenorphine; Hydrocodone [start with a 20–

30% lower hydrocodone dose when used
Page | 264
NERVOUS SYSTEM
An aliphatic-derived, phenothiazine that is
used for treating schizophrenia, and is
effective for other psychoses and
agitated states.
Indications: Schizophrenia and some other
psychotic disorders, mania,
psychomotor agitation and violent
behavior; adjunct in severe anxiety.
Contraindications: Known hypersensitivity to
chlorpromazine or any component of the
formulation; impaired consciousness
due to CNS depression; bone marrow
depression; severe cardiovascular
disease; subcortical brain damage;
concomitant use of CNS depressants;
pheochromocytoma; lactation.
Dose:
Schizophrenia and other psychoses, mania,
psychomotor agitation, violent behavior,
severe anxiety (adjunct), by mouth,
ADULT, initially 10 to 25 mg 3 times daily
or 75 mg at night, adjusted according to
response to usual maintenance dose of
75-300 mg daily (but up to 1 g daily may
be required in psychoses); ELDERLY (or
debilitated patients) one-third to half of
the adult dose; CHILD 6-12 years, one-
third to half of the adult dose (maximum,
75 mg daily); CHILD (childhood
schizophrenia and autism) 1-5 years,
500 micrograms/kg every 4-6 hours
(maximum, 40 mg daily).
For relief of acute symptoms, by deep IM
injection, ADULT, 25-50 mg, may repeat
in 1 hour; CHILD, refer to a specialist.
Dose Adjustment:
Hepatic Impairment:
Consider dose reduction in mild impairment.
Avoid use in moderate to severe
impairment.
Precautions:
WARNING: Patients with dementia-related
psychosis who are treated with
antipsychotic drugs are at increased risk
for death due to cardiovascular cause
(e.g., heart failure or sudden death) or
infections (e.g., pneumonia). Not for
dementia-related psychosis.
Patients >70 years of age (may cause
hypothermia); Parkinsonism; respiratory
disease; epilepsy; acute infections;
history of jaundice; hypothyroidism,
myasthenia gravis; prostatic
hypertrophy; angle-closure glaucoma;
cardiovascular and cerebrovascular
disorders; renal impairment (avoid use if
severe; start with small doses; increased
cerebral sensitivity); hepatic impairment
(avoid if severe; can precipitate coma,
hepatotoxic); the elderly (particularly in
very hot and very cold weather; reduce
dose); avoid abrupt withdrawal; the
patient should remain in supine position,
and BP monitored, for 30 minutes after
IM injection (due to risk of hypotension).
Pregnancy (third trimester: extrapyramidal
effects in neonate have been
occasionally reported).
SKILLED TASKS. May impair ability to perform
skilled tasks, e.g., operating machinery
or driving.
NOTE: Owing to the risk of contact
sensitization, pharmacists, nurses, and
other health workers should avoid direct
contact with chlorpromazine; tablets
should not be crushed and solutions
should be handled with care.
Adverse Drug Reactions:
Common: Agitation, anxiety, blurred vision,
constipation, dry mouth, extrapyramidal
side effects (e.g., Parkinsonian
symptoms, dystonia, akathisia, tardive
dyskinesia), hyperprolactinemia (e.g.,
galactorrhea, gynecomastia,
amenorrhea or infertility), mydriasis,
nausea, orthostatic hypotension,
sedation, sexual adverse effects,
tachycardia, urinary retention, weight
gain.
Less Common to Rare: Agranulocytosis,
allergic reactions, anemia, arrhythmias,
cardiac arrest, changes in ECG,
cholestatic jaundice, corneal and lens
opacities, dysarthria, dysphagia, hepatic
fibrosis, hyperthermia, hypothermia,
increased blood glucose, neuroleptic
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NERVOUS SYSTEM
malignant syndrome, neutropenia, Epinephrine – antagonism of hypertensive
photosensitivity reactions (phototoxicity, effect.
and hyperpigmentation), priapism, Seizure-inducing drugs (see Appendix – Table
SIADH, SLE, sudden death, C for other drugs which may also cause
thrombocytopenia, venous seizures) – chlorpromazine may cause
thromboembolism (VTE). seizures; administration with these
drugs may increase this risk.
Drug Interactions:
Monitor closely with: Administration: May be taken with or without
Atropine – increased antimuscarinic adverse food; may be administered with meals to
effects (but reduced plasma reduce GI discomfort.
concentration of chlorpromazine). NOTE: Avoid skin contact with injection solution
CNS depressants (e.g., alcohol, sedatives and as there is a risk of contact dermatitis.
tranquilizers) – possibly enhanced CNS Avoid using crushed tablets for this
depression. reason and to reduce risk of direct
Diazepam – enhanced sedative effect. irritation to oral mucosa. In cases where
Drugs causing hypotension (e.g. amlodipine, there is no alternative, inject deeply into
atenolol, enalapril, furosemide, a large muscle mass. Give IV doses well
hydrochlorothiazide and ISDN) – diluted and by infusion.
antipsychotics can cause orthostatic
hypotension and may result in additional Pregnancy Category: C
hypotension when given with these
drugs. ATC Code: N05AA01
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, calcineurin
inhibitors, high-dose thiazide diuretics
and somatropin) – chlorpromazine can CLOZAPINE
increase blood glucose concentration, Rx
and may increase risk of hyperglycemia
if given with these drugs.
Oral: 25 mg and 100 mg tablet
Drugs with anticholinergic effects (see
Appendix – Table A) – chlorpromazine
has anticholinergic effects; NOTE: Only for rural and municipal health units
administration with these drugs with physicians who have undergone
increases the risk of adverse effects. training under the Mental Health
Methyldopa – enhanced hypotensive effect; Medicines Access Program (MHMAP)
increased risk of extrapyramidal effects. and qualified to prescribe
Metoclopramide – increased risk of psychopharmacologic medicines.
extrapyramidal effects.
Propranolol – this may increase
chlorpromazine concentration, Clozapine is a tricyclic dibenzodiazepine and
increasing risk of toxicity. an atypical antipsychotic with weak D2
blocking action. It is the only antipsychotic
Avoid concomitant use with:
Antacids (e.g., aluminum or magnesium documented to reduce suicide risk in
hydroxide) – these reduce absorption of patients with schizophrenia. It has 5-HT2A
chlorpromazine. antagonism which gives it little to no EPS
Artemether + lumefantrine – these may result and tardive dyskinesia risk, and dose not
to potentially hazardous interactions elevate prolactin. It is often reserved as a
when given concomitantly with last-line option due to the risk of developing
chlorpromazine. life-threatening and occasionally fatal

Page | 266
NERVOUS SYSTEM
agranulocytosis, as well as an increased
risk of seizures.
Indications: Management of treatment-
resistant schizophrenia; for reducing the
risk of recurrent suicidal behavior in
patients with schizophrenia and
schizoaffective disorder.
Contraindications: Uncontrolled epilepsy,
paralytic ileus, myeloproliferative disorders,
history of clozapine-induced
agranulocytosis or severe
granulocytopenia; severe CNS depression;
coma, bone-marrow disorders, alcoholic
and toxic psychoses, severe cardiac
disorders (e.g., myocarditis), history of
circulatory collapse.
Dose:
Treatment-resistant schizophrenia and for
reducing risk of recurrent suicidal behavior
in patients with schizophrenia and
schizoaffective disorder, by mouth, ADULT,
initially 25 mg daily in 2 divided doses,
slowly increase by 25–50 mg daily each day
to a target dose of 300–450 mg daily in
divided doses by the end of 2 weeks;
administer doses above 300 mg once daily
in divided doses; dose increases beyond
450 mg once daily should be done no more
frequently than once or twice weekly in
increments not exceeding 100 mg daily up
to a maximum dose of 900 mg once daily; if
dosing is interrupted for ≥48 hours, re-
initiate therapy at 12.5 mg once or twice
daily to minimize the risk of hypotension,
bradycardia, and syncope.
NOTE: Recommended dose is between 300–
800 mg once daily for at least 8 weeks as
an adequate trial in treatment-resistant
schizophrenia. If despite adequate dosing
and adherence there is no adequate
response, perform therapeutic drug
monitoring. Plasma levels above 350
nanograms/mL have been associated with
treatment response.
Dose Adjustments:
Geriatric:
May tolerate lower doses better. Initiate with
12.5 mg once daily for 3 days, then increase
to 25 mg once daily for 3 days as tolerated,
may further increase, as tolerated, in
increments of 12.5–25 mg daily every 3
days to desired response, up to a maximum
of 700 mg daily.
Renal Impairment:
Avoid in severe impairment.
Hepatic Impairment:
Avoid in symptomatic liver disease, progressive
liver disease and hepatic failure. Monitor
hepatic function regularly.
Precautions:
WARNING:
Agranulocytosis. Associated with a
significant risk of potentially life-
threatening agranulocytosis. Reserved
use in the treatment of severely-ill
patients with schizophrenia who fail to
show an acceptable response to
adequate courses of standard
antipsychotic drug treatment, or for
reducing the risk of recurrent suicidal
behavior in patients with schizophrenia
and schizoaffective disorder who are
judged to be at risk of re-experiencing
suicidal behavior. Patients must have
a baseline absolute neutrophil count
(ANC) before initiation of treatment, as
well as regular ANCs during treatment
and for at least 4 weeks after
discontinuation of treatment.
Seizures. Use caution when administering
to patients with a history of seizures or
other predisposing factors. Advise
patients not to engage in any activity
where sudden loss of consciousness
could cause serious risk to themselves
or others.
Page | 267
NERVOUS SYSTEM
Fatal myocarditis and cardiomyopathy.
Discontinue immediately when
myocarditis is suspected. Re-challenge
with clozapine patients with clozapine-
related myocarditis or cardiomyopathy.
Orthostatic hypotension, with or without
syncope, can occur. Rarely, collapse
can be profound and be accompanied
by respiratory and/or cardiac arrest. In
case of a brief interval off clozapine,
i.e. 2 or more days since the last dose,
resume treatment with 12.5 mg once
or twice daily.
Use with caution when administered
concurrently with benzodiazepine or
any other psychotropic drug since
collapse, respiratory arrest and cardiac
arrest has occurred in this
combination.
Elderly patients with dementia-related
psychosis treated with antipsychotic
drugs are at an increased risk of
death. Clozapine is not approved for
use in patients with dementia-related
psychosis.
Anticholinergic effects (e.g., constipation,
xerostomia, blurred vision, urinary
retention; use is associated with increased
risk of paralytic ileus, bowel obstruction,
fecal impaction, bowel perforation, and in
rare cases death); fever (benign transient
temperature elevation >38°C or 100.4°F);
neuroleptic malignant syndrome; impaired
temperature regulation.
CNS depression; extrapyramidal symptoms
e.g. acute dystonic reactions,
pseudoparkinsonism, akathisia, and
tardive dyskinesia; risk of dystonia may be
greater with increased doses); falls; suicidal
ideation; QT prolongation (ventricular
arrhythmias; cardiac arrest and sudden
death).
Dyslipidemia; eosinophilia; hyperglycemia
(associated with ketoacidosis,
hyperosmolar coma, or death); sialorrhea
(drooling, skin irritation and infections,
aspiration pneumonia, chronic sleep
Page | 268
disturbances with daytime fatigue and
somnolence, painful swelling of the salivary
glands, and symptomatic aerophagia with
resultant gas bloating, pain, and flatus may
also develop); thromboembolism (deep vein
thrombosis and pulmonary embolism,
some fatal).
Esophageal dysmotility or aspiration;
hepatotoxicity (severe, life-threatening,
sometimes fatal, including hepatic failure,
hepatic necrosis, and hepatitis); weight
gain.
Acute infectious or inflammatory processes;
benign ethnic neutropenia; cardiovascular
disease; glaucoma; prostate; renal
impairment.
Smokers (decreases clozapine concentration;
may require twice the daily dose to obtain
an equivalent concentration; smoking
cessation may cause toxicity in patients
stabilized on clozapine; monitor change in
smoking patterns).
Elderly (more susceptible to adverse effects;
potentially inappropriate in the elderly;
avoid use in patients ≥65 years with
dementia due to an increased risk of
mortality and cerebrovascular accidents, a
greater rate of cognitive decline, and
potential to cause or exacerbate SIADH or
hyponatremia, unless all non-
pharmacologic options have failed or are
not possible or the patient is threatening
substantial harm to self or to others).
Pregnancy (risk of abnormal muscle
movements and withdrawal symptoms in
newborns with fetal exposure during the
third trimester); lactation (monitor infant for
possible adverse effects).
SKILLED TASKS. May impair ability to perform
tasks, which require mental alertness, like
driving or operating machinery.
Adverse Drug Reactions:
Common: Tachycardia, hypotension,
hypertension, syncope, drowsiness,
sedation, dizziness, insomnia, headache,
agitation, restlessness, vertigo, akinesia,
disturbed sleep, nightmares, akathisia,
NERVOUS SYSTEM
confusion, seizure (dose related), fatigue, Rare: Changes in body thermoregulation.
tremor, hypersalivation (can be severe),
diaphoresis, skin rash, weight gain, Drug Interactions:
sialorrhea, constipation, nausea, vomiting, Monitor closely with:
dyspepsia, xerostomia, abdominal distress, Antihypertensives, CNS Depressants (central
heartburn, diarrhea, leukopenia, effects) – Clozapine enhances
neutropenia, eosinophilia, urine therapeutic effects
abnormality, hypokinesia, muscle rigidity, Methylphenidate, Metoclopramide (sleepiness
visual disturbance. and dizziness)
Less Common: Agranulocytosis, abnormal Lithium (neurotoxic effect)- Increases risk of
electroencephalogram, angioedema, adverse or toxic effects of Clozapine
aspiration, bradycardia, cardiac arrhythmia, Acetylcholinesterase Inhibitors
cardiac failure, cardiomyopathy (usually (extrapyramidal symptoms),
dilated), cataplexy, cerebrovascular Antihypertensives (hypotension)
accident, cholestasis, colitis, deep vein Glucagon (GI adverse effects)
thrombosis, delirium, diabetes mellitus, Topiramate, Myelosuppressive Agents
dyschromia, dysphagia, enlargement of (bone marrow suppression)
salivary glands, erythema multiforme, fecal QTc-prolonging Agents (torsades de
impaction, gastroenteritis, pointes)
granulocytopenia, esophageal dysmotility, Serotonin Modulators (neuroleptic
hepatic cirrhosis, hepatic fibrosis, hepatic malignant syndrome; serotonin syndrome)
insufficiency, hepatic necrosis, hepatitis, SSRIs (psychomotor impairment) –
hypersensitivity reaction, hepatotoxicity, Clozapine increases risk of adverse or toxic
hyperglycemia associated with ketoacidosis effects of these drugs
or hyperosmolar coma or death, Nitroglycerin – Clozapine decreases
hyperuricemia, hyponatremia, interstitial absorption (decreases dissolution of
nephritis (acute), intestinal obstruction, sublingual nitroglycerin tablets)
jaundice, ketoacidosis, leukocytosis, liver Antidiabetics, Phenylephrine, Prokinetics,
injury, liver steatosis, lower respiratory tract Secretin
infection, mitral valve insufficiency, Amphetamines (stimulant effect)
myasthenia syndrome, myocardial Anticholinergics (anticholinergic effect)
infarction, myocarditis, myoclonus, Epinephrine (reverses pressor effect)
neuroleptic malignant syndrome, nocturnal Guanethidine (antihypertensive effects) –
enuresis, obsessive compulsive disorder, Clozapine reduces therapeutic effects of
obstructive orthostatic hypotension, these drugs
palpitations, sleep apnea, pancreatitis
(acute), paralytic ileus, paresthesia, Avoid concomitant use with:
pheochromocytoma (pseudo), periorbital Increases risk of adverse or toxic effects of the
edema, pleural effusion, pneumonia, following drugs:
priapism, pulmonary embolism, prolonged Agranulocytosis-inducing Drugs
QT interval (dose-dependent), renal failure, (agranulocytosis)
psychosis (exacerbated), retrograde Other Antipsychotics (increased
ejaculation, rhabdomyolysis, sepsis, skin hospitalization rates and length of stay;
photosensitivity, sialadenitis, status increased mortality; QTc prolongation;
epilepticus, SJS, systemic lupus torsades de pointes)
erythematosus, syncope, tardive
dyskinesia, thrombocytopenia, Administration: May be taken with or without
thrombocytosis, torsade de pointes, food.
vasculitis, weight loss.
Page | 269
NERVOUS SYSTEM
Do NOT discontinue abruptly because of the
possibility of withdrawal and rebound
psychosis. Perform discontinuation or
cross-titration gradually over 1–2 weeks to
minimize the potential of withdrawal,
rebound psychosis, extrapyramidal side
effects, cholinergic rebound, rebound
insomnia, and unwanted pregnancy, unless
safety concerns require a more rapid
withdrawal.
Pregnancy Category: B
ATC Code: N05AH02
FLUPHENAZINE
Rx
Inj.:25 mg/mL (as decanoate), 1 mL ampule
and 10 mL vial (IM)
NOTE: Only for rural and municipal health units
with physicians who have undergone
training under the Mental Health
Medicines Access Program (MHMAP)
and qualified to prescribe
psychopharmacologic medicines.
Fluphenazine is a phenothiazine typical
antipsychotic formulated as a long-acting
injectable for use in patients with
schizophrenia who have difficulty with
adherence to oral medications. It blocks
brain dopamine (D2) receptors in the
mesolimbic system and decreases the
release of hypothalamic and hypophyseal
hormones.
Indications: Management of psychotic
disorders
Contraindications: Comatose state; CNS
depression; children <12 years; hepatic
disease; blood dyscrasias; bone marrow
suppression; subcortical brain injury with or
without hypothalamic damage; marked
cerebral atherosclerosis;
Page | 270
pheochromocytoma; pregnancy (third
trimester); lactation
Dose:
Psychotic disorders, by IM injection, ADULT
(stabilized on oral fluphenazine), 12.5
mg/0.5 mL to 25 mg/1 mL into the deltoid
or gluteal muscle; determine subsequent
doses and intervals based on patient’s
response; average dosing is usually 6.25–
25 mg every 2 weeks or 50 mg/2 mL not
longer than every 4 weeks; if doses >50 mg
are needed, increase cautiously in 12.5 mg
up to a maximum of 100 mg per dose.
Dose Adjustments:
Geriatric:
Use with caution and initiate with lower dose
Renal Impairment:
Use with caution and titrate slower. Monitoring
is recommended.
Hepatic Impairment:
Avoid in hepatic failure. Can precipitate coma.
Phenothiazines are hepatotoxic.
Precautions:
WARNING: NOT approved for the treatment
of patients with dementia-related
psychosis. Elderly patients with
dementia-related psychosis treated
with antipsychotic drugs are at an
increased risk of death, mostly
associated with cardiovascular
diseases (e.g. heart failure, sudden
death) or infections (e.g. pneumonia).
Altered cardiac conduction (life-threatening
arrhythmias); orthostatic hypotension;
cardiovascular disease; respiratory
disorder; blood dyscrasias (agranulocytosis,
neutropenia, and leukopenia, some fatal).
Anticholinergic effects (e.g., constipation,
xerostomia, blurred vision, urinary
retention); pheochromocytoma;
hyperprolactinemia; temperature regulation
(impaired core body temperature
NERVOUS SYSTEM
regulation); neuroleptic malignant tachycardia, variable blood pressure,
syndrome. akathisia, bizarre dream, cerebral edema,
CNS depression; extrapyramidal symptoms depression, disruption of body temperature
(pseudoparkinsonism, acute dystonic regulation, dizziness, drowsiness, dystonia,
reactions, akathisia, and tardive excitement, headache, hyperreflexia,
dyskinesia; risk of dystonia may be greater lethargy, Parkinsonian-like syndrome,
with increased doses); Parkinson disease; tardive dyskinesia, restlessness, dermatitis,
seizure disorder; ocular effects (cause eczema, erythema, pruritus, skin
pigmentary retinopathy, and lenticular and photosensitivity, seborrhea, skin
corneal deposits); glaucoma. pigmentation, skin rash, urticaria
Esophageal dysmotility or aspiration; hepatic amenorrhea, change in libido, galactorrhea,
effects (liver damage and jaundice of the gynecomastia, increased serum prolactin,
cholestatic type of hepatitis); hepatic menstrual disease, SIADH (syndrome of
impairment; renal impairment; masking. inappropriate antidiuretic hormone
Elderly (increased risk of tardive dyskinesia, secretion), weight gain anorexia,
especially among women; potentially constipation, paralytic ileus, salivation,
inappropriate in the elderly; avoid use in xerostomia, bladder paralysis, ejaculatory
patients ≥65 years with dementia due to an disorder, impotence, mastalgia,
increased risk of mortality and agranulocytosis, eosinophilia, leukopenia,
cerebrovascular accidents, a greater rate of lens disease, nonthrombocytopenic
cognitive decline, and potential to cause or purpura, urinary incontinence,
exacerbate SIADH or hyponatremia, unless pancytopenia, thrombocytopenia,
all nonpharmacologic options have failed or hepatotoxicity, muscle spasm (neck),
are not possible or the patient is systemic lupus erythematosus, tremor
threatening substantial harm to self or to (fingers), blurred vision, corneal changes,
others). glaucoma, retinitis pigmentosa, polyuria,
Pregnancy (risk of abnormal muscle asthma, laryngeal edema, nasal
movements and withdrawal symptoms in congestion.
newborns with fetal exposure during the Rare: Cholestatic jaundice, cornea and lens
third trimester); lactation (tardive pigmentation, blood dyscrasias
dyskinesia, dystonia, and sedation have (leukocytosis or leukopenia, eosinophilia,
been observed in nursing infants). thrombocytopenia, agranulocytosis),
seizures, changes in body
SKILLED TASKS. May impair ability to perform thermoregulation, neuroleptic malignant
tasks, which require mental alertness, like syndrome.
driving or operating machinery.
NOTE: Patients taking this drug may
Adverse Drug Reactions: experience weight gain and/or sedation.
Common: Neuroleptic-induced deficit
syndrome, akathisia, priapism, Drug Interactions:
extrapyramidal symptoms, parkinsonism, Monitor closely with:
tardive dyskinesia, tardive dystonia, CNS depressants – with additive effects
galactorrhea, amenorrhea, sedation, dry
mouth, urinary retention, decreased Atropine or related compounds – with additive
sweating, sexual dysfunction, syncope, red cholinergic effects
to red-brown urine, photosensitivity, long-
term skin pigmentation changes. Anticholinergics (anticholinergic effects) –
Less Common: Jaundice, cardiac arrhythmia, enhances effects of fluphenazine
edema, hypertension, hypotension,

Page | 271
NERVOUS SYSTEM
Antihypertensives [except Guanethidine], Beta
Blockers [except Atenolol, Nadolol]
Vasopressors, e.g. Epinephrine (lowers
blood pressure)
Thiopental (hypotensive effect; CNS
excitatory effect) – Fluphenazine enhances
therapeutic effect of these drugs
Diuretics (hypotension)
Epinephrine (low blood pressure)
Methylphenidate, Metoclopramide
(sleepiness and dizziness)
Lithium (neurotoxic effect)- Increases risk of
adverse or toxic effects of Fluphenazine:
Diuretics (hypotension)
Glucagon (GI adverse effects)
Hypotension-associated Agents
(hypotension)
Photosensitizing Agents (photosensitizing
effect)
QTc-prolonging Agents (torsades de
pointes) Serotonin Modulators (neuroleptic
malignant syndrome; serotonin syndrome)
SSRIs (psychomotor impairment)
Topiramate (hyperthermia) - Fluphenazine
increases risk of adverse or toxic effects
Antacids - Reduces absorption of Fluphenazine
Nitroglycerin – Drug decreases absorption
(decreases dissolution of sublingual
nitroglycerin tablets)
Amphetamines (stimulant effect)
Levodopa, Dopamine Agonists, Prokinetics,
Secretin – with reduced therapeutic effect
of these drugs:
Avoid concomitant use with:
Potassium Salts (Oral) – delayed gastric
emptying time
CNS Depressant [high dose] (CNS depression)
– enhances effects of fluphenazine
Other Antipsychotics - Fluphenazine increases
risk of adverse or toxic effects (e.g.,
increased hospitalization rates and length
of stay; increased mortality; QTc
prolongation; torsades de pointes)
Page | 272
Administration: Administer by IM injection
using a dry syringe and needle of ≥21
gauge. A wet needle or syringe may cause
the solution to become cloudy. Z-track
injection techniques are recommended to
limit leakage after injections.
Do NOT discontinue abruptly because of the
possibility of withdrawal and rebound
psychosis. Discontinue or cross-titrate
gradually to minimize the potential of
withdrawal, rebound psychosis,
extrapyramidal side effects, cholinergic
rebound, rebound insomnia, and unwanted
pregnancy, unless safety concerns require a
more rapid withdrawal.
Pregnancy Category: C
ATC Code: N05AB02
HALOPERIDOL
Rx
Oral: 2 mg, 5 mg, and 10 mg tablet
Inj.: 5 mg/mL, 1 mL ampul (IM)
50 mg/mL, 1 mL (oily) ampul (IM)
(as decanoate)
NOTE: Only for rural and municipal health units
with physicians who have undergone
training under the Mental Health
Medicines Access Program (MHMAP)
and qualified to prescribe
psychopharmacologic medicines.
A butyrophenone-derived, first-generation
(typical) antipsychotic drug having
potent dopamine receptor antagonist
activity, and is characterized by fewer
autonomic (sedative and
antimuscarinic) effects; but has greater
extrapyramidal side-effects.
Indications: Schizophrenia, acute and chronic
psychoses; mania; short-term adjunctive
management of psychomotor agitation,
violent behavior and severe anxiety;
Tourette’s syndrome.
NERVOUS SYSTEM
Contraindications: Comatose states; impaired
consciousness due to CNS depression;
Parkinson’s syndrome or preexisting
Parkinson-like symptoms; bone marrow
depression; porphyria;
pheochromocytoma; basal ganglia
disease; poorly controlled seizures.
Dose:
Acute psychotic conditions, by IM injection,
ADULT, initially 2-10 mg (half of the adult
dose in elderly or debilitated patients; up
to 18 mg in severely affected patients);
subsequent doses every 4-8 hours
according to response (up to every hour
if necessary) up to a maximum of 18 mg
daily; CHILD, use is not recommended.
Chronic psychoses, by mouth, ADULT, 1-5 mg
2 or 3 times daily (maximum, 30 mg
daily); long-acting IM, 50-300 mg every 4
weeks; by mouth, CHILD >5 years,
initially 0.25-0.5 mg once daily, increase
to 0.15 mg/kg daily (maximum, 5 mg).
Schizophrenia and other psychoses, mania,
short-term adjunctive management of
psychomotor agitation, violent behavior
and severe anxiety, by mouth, ADULT,
1.5-3 mg 2-3 times daily (half of the
adult dose in elderly or debilitated
patients; 3-5 mg 2-3 times daily in
severely affected or resistant patients;
up to 30 mg daily in resistant
schizophrenia); CHILD, 25-50
micrograms/kg daily in 2 divided doses
(maximum, 10 mg daily).
Tourette’s syndrome, by mouth, CHILD >5
years, initially 0.25-0.5 mg once daily,
increase to 0.05 mg/kg daily (maximum,
5 mg).
NOTE: May be given in 2 or 3 divided doses.
Dose Adjustments:
Elderly:
Halve the adult dose.
Renal Impairment:
For mild to moderate renal impairment, dose
reduction is warranted due to increased
cerebral sensitivity (start with small
dose); for severe impairment, the patient
should be referred to a specialist.
Precautions:
WARNING: Patients with dementia-related
psychosis who are treated with
antipsychotic drugs are at increased risk
for death due to cardiovascular cause
(e.g., heart failure or sudden death) or
infections (e.g., pneumonia). Not for
dementia-related psychosis.
Avoid abrupt withdrawal of treatment (should
always be gradual, and closely
monitored to avoid risk of acute
withdrawal syndromes or rapid relapse);
in patients with Parkinson’s disease
(may be exacerbated), epilepsy (and
conditions predisposing to seizure
disorders), depression, myasthenia
gravis, prostatic hypertrophy,
hypothyroidism, or a susceptibility to
angle-closure glaucoma; dose
adjustment may be necessary if the
patient started or stopped smoking
during treatment; thyrotoxicosis;
arteriosclerosis, and cardiovascular
disorders (an ECG may be required),
including risk for prolonged QT interval;
metabolic disturbances (hypokalemia,
hypocalcemia or hypomagnesemia);
cerebrovascular disorders, respiratory
disease, acute infections.
Hepatic impairment (avoid use; antipsychotic
drugs can precipitate coma if used in
hepatic impairment); leukopenia (blood
count is required if with unexplained
fever or infection); photosensitization
may occur with higher doses (patients
should avoid direct sunlight); history of
jaundice; hypotension (when
administered IM).
Elderly, particularly in very hot or very cold
weather (associated with a small
increased risk of mortality, and an
increased risk of stroke or transient
ischemic attack; risk of postural
hypotension, and to hyper- and
hypothermia); children and adolescents.
Pregnancy (third trimester: depresses
neonatal respiration; extrapyramidal
effects and withdrawal syndrome have
been reported); breastfeeding (possible
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NERVOUS SYSTEM
risk of adverse effects; monitor infant for CNS depressants (e.g., alcohol, sedatives, and
drowsiness). tranquilizers) – haloperidol causes CNS
SKILLED TASKS. May impair ability to perform depression; administration with these
skilled tasks, such as operating drugs may lead to enhanced adverse
machinery or driving. effects (e.g., sedation).
Codeine – enhanced sedative and hypotensive
Adverse Drug Reactions: effect.
NOTE: Haloperidol has less sedative effects, Drugs increasing blood glucose concentration
and fewer hypotensive and (e.g., glucocorticoids, other
anticholinergic symptoms. antipsychotics, calcineurin inhibitors,
Common: Constipation, depression, dryness of high-dose thiazide diuretics and
mouth, EPS, specifically acute dystonia somatropin) – haloperidol can increase
and akathisia; increased weight, blood glucose concentration, and may
injection site reactions, masked facies, increase risk of hyperglycemia if given
muscle rigidity, Parkinsonism, salivary with these drugs.
hypersecretion, sedation, sexual Drugs which reduce blood pressure (see
dysfunction, somnolence, tremor. Appendix – Table D) – antipsychotics
Less Common: Dyspnea, edema, nausea, can cause hypotension and, if given with
vomiting. these drugs, may have enhanced
Rare: Agranulocytosis, anaphylaxis, hypotensive effects.
bronchospasm, convulsions, Fluoxetine – increased plasma haloperidol
gynecomastia, headache, hepatitis, concentration.
hypersensitivity reactions, hypertension, Lithium – increased risk of extrapyramidal
hyperthermia, hypoglycemia, effects.
hypothermia, inappropriate antidiuretic Metoclopramide – increased risk of
hormone secretion, neuroleptic extrapyramidal effects.
malignant syndrome, photosensitivity Morphine – enhanced hypotensive and
reactions and pigmentation, priapism, sedative effects.
psychotic disorders, QT prolongation, Procainamide – increased risk of ventricular
Stevens-Johnson syndrome, sweating, arrhythmias.
toxic epidermal necrolysis, weight loss. Quinidine – increased risk of ventricular
arrhythmias.
Drug Interactions: Reserpine – increased risk of extrapyramidal
NOTE: Haloperidol is a substrate for CYP effects.
enzymes (see Appendix); its plasma Ritonavir – possibly increased haloperidol
concentration may be affected by concentration.
various drugs, which act as enzyme
inducers or inhibitors. Avoid concomitant use with:
Anticholinergic drugs or other drugs with
Monitor closely with: anticholinergic effects (see Appendix –
Amitriptyline – increased plasma amitriptyline Table A) – haloperidol has
concentration; may increase the risk of anticholinergic effects; administration
ventricular arrhythmias with these drugs increases the risk of
Carbamazepine – antagonism of adverse effects (including central
anticonvulsant effect (convulsive anticholinergic delirium that is often
threshold lowered); accelerated missed); avoid these combinations if
metabolism of haloperidol, reducing its possible (if a combination is required,
plasma concentration. monitor the patient and reduce dose if
Clomipramine – its plasma concentration is necessary).
increased, possibly increased risk of Artemether + lumefantrine – these may result
ventricular arrhythmias. to potentially hazardous interactions

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NERVOUS SYSTEM
when given concomitantly with
haloperidol.
Atropine – this may reduce effects of
haloperidol.
Biperiden – this may reduce effects of
haloperidol.
Dopamine – antagonism of hypertensive
effect.
Dopamine agonists (e.g., cabergoline,
pergolide and levodopa) – antagonism;
haloperidol can reduce their therapeutic
effect.
Drugs which prolong QT interval (see Appendix
– Table B) and other Antimalarials – the
QT interval may increase if haloperidol is
given with these drugs; increasing the
risk of arrhythmias.
Ephedrine – antagonism of hypertensive
effect.
Epinephrine – antagonism of hypertensive
effect.
Ethosuximide – antagonism of anticonvulsant
effect (convulsive threshold lowered).
Levodopa – haloperidol antagonizes the
effects of levodopa.
Phenobarbital – antagonism of anticonvulsant
effect (convulsive threshold lowered);
accelerated metabolism of haloperidol,
reducing its plasma concentration.
Phenytoin – antagonism of anticonvulsant
effect (convulsive threshold lowered).
Rifampicin – accelerated metabolism of
haloperidol, reducing its plasma
concentration.
Seizure-inducing drugs (see Appendix – Table
C) – antipsychotics can possibly lower
seizure threshold; administration with
these drugs may increase the risk of
seizures.
Valproic acid – antagonism of anticonvulsant
effect (convulsive threshold lowered).
Administration: May be taken with or without
food; may be taken with meals to
minimize GI irritation; patients should
remain supine, and the BP monitored,
for 30 minutes after IM injection. For
long-acting injection, divided injection
volumes >3 mL in half, and give at 2
sites.
Pregnancy Category: C
ATC Code: N05AD01
LITHIUM CARBONATE
Rx
Oral: 450 mg MR tablet
NOTE: Only for rural and municipal health units
with physicians who have undergone
training under the Mental Health
Medicines Access Program (MHMAP)
and qualified to prescribe
psychopharmacologic medicines.
The mechanism of action of Lithium Carbonate
is unclear, but is effective in managing
mania, bipolar disorder, and recurrent
unipolar depression.
Indications: First-line treatment of manic
episodes of bipolar disorder; maintenance
treatment for bipolar disorder with a history
of mania; maintenance treatment for
manic-depressive patients with a history of
mania; manic episodes of manic-depressive
illness.
Contraindications: Severe kidney disease;
severe cardiovascular disease; Brugada
syndrome; severe debilitation; severe
dehydration; sodium depletion.
Dose:
Treatment for bipolar disorder I (acute mania,
acute depression), by mouth, ADULT,
initially 450 mg twice daily, slowly titrate
dose based on efficacy, tolerability, and
serum lithium concentrations to an average
of 900–1,800 mg daily in 2 divided doses;
maintenance treatment of bipolar disorders
I and II, initially 500 mg daily, increase
gradually every 7 days until target blood
level is reached; maximum of 600-1200 mg
daily.
Manic episodes of bipolar disorder, by mouth,
ADULT, initially 450 mg twice daily, slowly
titrate dose based on efficacy, tolerability,
and serum lithium concentrations to an
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NERVOUS SYSTEM
average of 1,800 mg daily in 2 divided
doses; CHILD ≥12 years, initially 1.8 g daily
in 2–3 divided doses.
Dose Adjustments:
Geriatric:
Lower doses and lower serum lithium
concentrations are often adequate and
advisable.
Renal Impairment:
Not recommended for use in patients with
severe renal impairment.
In CrCl 10–50 mL/minute and in patients on
continuous renal replacement therapy
(CRRT), administer 50–75% of dose.
In CrCl <10 mL/minute, administer 25–50% of
dose.
In End-stage renal disease (ESRD) with
hemodialysis, administer dose after
dialysis.
Precautions:
WARNING: Lithium toxicity is closely
related to serum lithium levels and can
occur at doses close to therapeutic
levels. Facilities for prompt and
accurate serum lithium determinations
should be available before initiating
therapy. Monitor trough lithium plasma
levels frequently (1.0 and 1.5 mEq/L
for acute treatment and 0.6 and 1.2
mEq/L for chronic treatment)
CNS depression; depression; suicidal ideation;
heart failure, e.g., reversible myocardial
toxicity; cardiovascular disease;
hypercalcemia; hypothyroidism; thyroid
disease; renal effects e.g. renal impairment,
dehydration.
Debilitated patients and Elderly (lithium
toxicity); women (hypothyroidism).
SKILLED TASKS. May impair ability to perform
tasks, which require mental alertness, like
driving or operating machinery.
Page | 276
Adverse Drug Reactions:
Common: AV block or other conduction issues,
bradyarrhythmia, ECG changes,
arrhythmias, QTc prolongation, ataxia,
dysarthria, delirium, tremor, memory
problems, diarrhea, acne, psoriasis,
alopecia, hypothyroidism, weight gain,
nausea, dry mouth, polyuria, benign
leukocytosis.
Less Common: End stage renal disease,
hypothyroidism (children, adolescents),
abnormal T waves, bradycardia, chest
tightness, circulatory shock, cold
extremities, edema, hypotension,
myxedema, startled response, sinus node
dysfunction, syncope, ataxia, blackout
spells, cogwheel rigidity, coma, confusion,
dizziness, drowsiness, dystonia, EEG
pattern changes, extrapyramidal reaction,
fatigue, hallucination, headache,
hyperactive deep tendon reflex, hypertonia,
involuntary choreoathetoid movements,
lethargy, memory impairment, local
anesthesia, loss of consciousness, metallic
taste, pseudotumor cerebri, psychomotor
retardation, reduced intellectual ability,
restlessness, salty taste, sedation, seizure,
slowed intellectual functioning, slurred
speech, stupor, tics, vertigo, worsening of
organic brain syndromes, blue-gray skin
pigmentation, dermal ulcer, exacerbation of
psoriasis, folliculitis, pruritus, skin rash,
xerosis, albuminuria, dehydration, diabetes
insipidus, euthyroid goiter, glycosuria,
hypercalcemia, hyperparathyroidism,
increased radioactive iodine uptake,
hyperthyroidism, polydipsia, weight loss,
abdominal pain, anorexia, dental caries,
diarrhea, dysgeusia, dyspepsia, excessive
salivation, flatulence, gastritis, vomiting,
sialadenitis, sialorrhea, swelling of lips,
xerostomia, impotence, incontinence,
leukocytosis, angioedema, joint swelling,
muscle hyperirritability, neuromuscular
excitability, polyarthralgia, tremor, blurred
vision, exophthalmos, nystagmus, transient
scotoma, tinnitus, oliguria, polyuria, fever.
Rare: Lithium toxicity, renal impairment
(interstitial nephritis), nephrogenic diabetes
NERVOUS SYSTEM
insipidus, acute tubular necrosis,
cardiovascular changes, sick sinus
syndrome, bradycardia, hypotension,
nephrotic syndrome, T wave flattening and
inversion, pseudotumor cerebri, seizures,
chronic kidney disease, syndrome of
irreversible lithium-effectuated
neurotoxicity (SILENT), myasthenia gravis.
NOTE: Patients taking this drug may
experience weight gain and/or sedation.
Drug Interactions:
Monitor closely with:
Linezolid, Opioids, SSRIs e.g., Fluoxetine
(serotonergic effect)
Neuromuscular Blockers (prolonged
effects) Potassium Iodide (hypothyroid
effect)
QTc-prolonging Agents – Lithium enhances
therapeutic effect of the following drugs
Antipsychotics, CCBs e.g., Amlodipine,
Carbamazepine, Fosphenytoin, MAOIs
[except Moclobemide], Methyldopa,
Phenytoin, Metronidazole, Sargramostim
(myeloproliferative effects) - Increase risk of
adverse or toxic effects of lithium carbonate
Haloperidol (encephalopathic syndrome),
Linezolid, Opioids,
Serotonin Modulators [except Nicergoline]
(serotonin syndrome)
SSRIs e.g. Fluoxetine (serotonin syndrome)
Metoclopramide (serotonin syndrome;
neuroleptic malignant syndrome)
TCAs e.g., Amitriptyline (neurotoxic effect)
Tramadol (seizures) – Lithium Increases
risk of adverse or toxic effects
Amphetamines (stimulatory effect)
Desmopressin – Lithium reduces their
therapeutic effect
Administration: Should be taken with food.
Maintain normal fluid and salt intake during
therapy.
Pregnancy Category: D
ATC Code: N05AN01
OLANZAPINE
Rx
Oral: 5 mg and 10 mg tablet
10 mg orodispersible tablet (ODT)
NOTE: Only for rural and municipal health units
with physicians who have undergone
training under the Mental Health
Medicines Access Program (MHMAP)
and qualified to prescribe
psychopharmacologic medicines.
A dibenzodiazepine-derived, second-
generation (atypical) antipsychotic,
which is a D1, D2, D4, 5-HT2, histamine-1-
, and muscarinic-receptor antagonist,
and is a homologue of clozapine.
Indications: Schizophrenia and related
psychoses; monotherapy or combination
therapy for mania, and prevent
recurrence in bipolar disorder.
Contraindications: Known hypersensitivity to
olanzapine or any component of the
formulation; myeloproliferative
disorders; severe CNS depression;
comatose states; lactation; for IM, heart
surgery.
Dose:
Bipolar I disorder (manic or mixed episodes),
by mouth, ADULT, start at 10 mg or 15
mg once daily; ADULT (in combination
with lithium or valproate), start at 10 mg
once daily; ADOLESCENT, start at 2.5-5
mg once daily adjusted to 10 mg once
daily.
Depressive episodes associated with bipolar I
disorder (in combination with fluoxetine),
by mouth, ADULT, start at 5 mg once
daily; CHILD and ADOLESCENT, start at
2.5 mg once daily.
Monotherapy for mania, by mouth, ADULT and
CHILD 12-18 years, 15 mg daily adjusted
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NERVOUS SYSTEM
to usual range of 5-20 mg daily (doses diabetes (risk of ketoacidosis); weight
>15 mg is given only after gain, hyperlipidemia;
reassessment; maximum, 20 mg daily). hyperprolactinemia.
NOTE: Olanzapine monotherapy is not Leukopenia, neutropenia, and agranulocytosis
indicated for the treatment of depressive (monitor CBC frequently; discontinuation
episodes associated with bipolar I should be considered at the first sign of
disorder and resistant depression decline in WBC with the absence of other
(treatment). causative factors); myeloproliferative
Resistant depression (treatment), by mouth, disease; bone marrow depression; blood
ADULT (in combination with fluoxetine), dyscrasia.
start at 5 mg once daily. Hepatic impairment (avoid use; antipsychotic
Schizophrenia, by mouth, ADULT >18 years, drugs can precipitate coma if used in
start at 5-10 mg once daily adjusted to hepatic impairment); history of jaundice.
usual range of 5-20 mg daily (doses >10 Neurologic disorders; cerebrovascular disease;
mg daily is given only after Parkinson’s disease (may be
reassessment; maximum, 20 mg daily); exacerbated), epilepsy (and conditions
CHILD, refer to a specialist. predisposing to seizure disorders),
depression, myasthenia gravis,
Dose Adjustments: Alzheimer’s disease; neuroleptic
Elderly: malignant syndrome (discontinue
If olanzapine is necessary, use low dose. immediately and monitor closely).
Renal Impairment: Prostatic hypertrophy; susceptibility to angle-
For mild to moderate renal impairment, dose closure glaucoma; severe respiratory
reduction is warranted due to increased disease; breast cancer; paralytic ileus;
cerebral sensitivity (start with small photosensitization may occur with higher
dose). For severe impairment, the doses (patients should avoid direct
patient should be referred to a specialist. sunlight).
Elderly, particularly in very hot or very cold
Precautions: weather (associated with a small
increased risk of mortality and an
WARNING: Elderly patients with dementia- increased risk of stroke or transient
related psychosis treated with ischemic attack; risk of postural
antipsychotic drugs (including hypotension, and to hyper- and
olanzapine) are at an increased risk of hypothermia); hypovolemia;
death due to cardiovascular (e.g., heart dehydration.
failure, sudden death) or infections (e.g., Pregnancy (in the third trimester: neonatal
pneumonia). lethargy, tremor, hypertonia,
Not for dementia-related psychosis. extrapyramidal effects and withdrawal
syndrome have been reported; use only
Withdrawal after therapy should always be if potential benefit outweighs risk);
gradual and closely monitored (to avoid breastfeeding (avoid use).
risk of acute withdrawal syndromes and NOTE: Check glucose tolerance if patient gains
rapid relapse); dose adjustment may be weight.
necessary if smoking was started, or SKILLED TASKS. May impair ability to perform
stopped, during treatment; skilled tasks, such as operating
cardiovascular disorders (an ECG may machinery or driving.
be required); suicide attempt (possibility
of suicide is inherent; requires close Adverse Drug Reactions:
supervision of high-risk patients). Common: Abdominal pain, abnormal gait,
Hyperglycemia (may be extreme in some akathisia, constipation, dizziness,
cases; associated with ketoacidosis, drowsiness, dry mouth, fatigue,
hyperosmolar coma and death); hallucinations, headache,

Page | 278
NERVOUS SYSTEM
hyperglycemia, increased appetite, mild
antimuscarinic effects, peripheral
edema, personality disorder, postural
hypotension, sedation and delirium after
long-acting injection; somnolence,
tremor, type 2 diabetes mellitus, weight
gain.
Less Common: Bradycardia, elevation of liver
aminotransferases, EPS, QT
prolongation, urinary incontinence.
Rare: Angle-closure glaucoma, hepatitis,
hypercholesterolemia, hyperlipidemia,
hypothermia, leukopenia, neuroleptic
malignant syndrome, neutropenia,
pancreatitis, priapism, rhabdomyolysis,
seizure, thrombocytopenia, urinary
retention, VTE.
Drug Interactions:
NOTE: Olanzapine is a substrate for CYP
enzymes (see Appendix); its
concentration may be affected by
various drugs, which act as enzyme
inducers or inhibitors.
Monitor closely with:
Antihypertensive agents – enhanced
antihypertensive effect.
Carbamazepine – this may increase
olanzapine’s metabolism, decreasing its
concentration and possibly its activity.
CNS depressants (e.g., alcohol, sedatives and
tranquilizers) – olanzapine causes CNS
depression; administration with these
drugs may enhance its adverse effects
(e.g., sedation).
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, other
antipsychotics, calcineurin inhibitors,
high-dose thiazide diuretics and
somatropin) – olanzapine can increase
blood glucose concentration, and may
increase risk of hyperglycemia if given
with these drugs.
Drugs which reduce blood pressure (see
Appendix – Table D) – antipsychotics
can cause hypotension and, if given with
these drugs, may have enhanced
hypotensive effects.
Lorazepam – increased somnolence with IM
olanzapine.
Ritonavir – this may increase the metabolism
of olanzapine, reducing its concentration
and possibly its activity.
Avoid concomitant use with:
Anticholinergic drugs or other drugs with
anticholinergic effects (see Appendix –
Table A) – olanzapine has
anticholinergic effects; administration
with these drugs increases the risk of
adverse effects (including central
anticholinergic delirium that is often
missed); avoid these combinations if
possible (if a combination is required,
monitor the patient and reduce dose if
necessary).
Dopamine agonists (e.g., cabergoline,
pergolide and levodopa) – antagonism;
olanzapine can reduce their therapeutic
effect.
Seizure-inducing drugs (see Appendix – Table
C) – antipsychotics can possibly lower
seizure threshold; administration with
these drugs may increase the risk of
seizures.
Administration: May be taken with or without
food. For long-acting IM, inject deep into
the gluteal muscle.
Pregnancy Category: C
ATC Code: N05AH03
RISPERIDONE
Rx
Oral: 1 mg, 2 mg, 3 mg and 4 mg tablet
1 mg and 2 mg orodispersible tablet
1 mg/mL oral solution, 100 mL
Inj.: 25 mg and 37.5 mg MR powder for
suspension, vial + 2 mL diluent in pre-
filled syringe (IM)
NOTE: Only for rural and municipal health units
with physicians who have undergone
training under the Mental Health
Medicines Access Program (MHMAP)
and qualified to prescribe
psychopharmacologic medicines.
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NERVOUS SYSTEM
NOTE: (IM) for use only by physicians who have
completed training in the proper
administration of risperidone.
A benzisoxazole-derived, second-generation
(atypical) antipsychotic having less side
effects, and is efficacious in treatment-
resistant patients and against negative
symptoms, such as emotional
withdrawal, poverty of speech and
movement, anhedonia and loss of
initiative.
Indications: Schizophrenia and related
psychoses (acute and chronic); short-
term treatment of acute mania;
maintenance treatment of bipolar I
disorder; persistent aggression;
behavior disturbance in dementia.
Contraindications: Known hypersensitivity to
risperidone and paliperidone, or any
component of the formulation; marked
CNS depression from any cause.
Dose:
Behavior disturbance in dementia, by mouth,
ADULT, 0.25 mg twice daily, increasing
by 0.25 mg daily every 2 or more days
(usual dose range: 0.5-1 mg twice daily).
Mania, by mouth, ADULT, initially 2 mg once
daily, increased if necessary in steps of
1 mg daily (usual dose range 1-6 mg
daily); ELDERLY, initially 500
micrograms twice daily increased in
steps of 500 micrograms twice daily to
1-2 mg twice daily; CHILD, refer to a
specialist.
Mania (maintenance), long-acting IM, ADULT,
25 mg every 2 weeks; increase if
necessary to maximum of 37.5-50 mg
every 2 weeks.
NOTE: Give supplemental oral antipsychotic for
the first 3 weeks. Do not adjust dose
more frequently than every 4 weeks.
Effects of a dose increase will not be
seen for 3 weeks.
Persistent aggression (in Alzheimer’s
dementia), by mouth, ADULT, initially
250 micrograms twice daily, increased
according to response in steps of 250
micrograms twice daily on alternate
Page | 280
days; usual dose, 500 micrograms twice
daily (up to 1 mg twice daily).
Psychoses (acute/chronic), by mouth, ADULT,
2 mg in 1-2 divided doses on first day
then 4 mg in 1-2 divided doses on
second day (slower titration appropriate
in some patients); usual dose range 4-6
mg daily; doses above 10 mg daily only if
benefit is considered to outweigh risk
(maximum, 16 mg daily); ELDERLY,
initially 500 micrograms twice daily
increased in steps of 500 micrograms
twice daily to 1-2 mg twice daily.
Schizophrenia, by mouth, ADULT, 1 mg twice
daily, increasing by 1 mg twice daily each
day (usual range: 4-6 mg daily; daily
doses greater than 4 mg increase the
risk of EPS); long-acting IM, ADULT, 25
mg every 2 weeks; increase if necessary
to maximum of 37.5-50 mg every 2
weeks. NOTE: Give supplemental oral
antipsychotic for the first 3 weeks. Do
not adjust dose more frequently than
every 4 weeks. Effects of a dose increase
will not be seen for 3 weeks.
Dose Adjustments:
Elderly:
Halve the usual starting and incremental
doses.
Renal Impairment:
For mild to moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Hepatic Impairment:
For mild to moderate hepatic impairment, use
half the usual starting and incremental
doses; for severe impairment, the
patient should be referred to a specialist.
Precautions:
WARNING: Elderly patients with dementia-
related psychosis treated with
antipsychotic drugs are at an increased
risk of death due to either cardiovascular
cause (e.g., heart failure or sudden
death) or infections (e.g., pneumonia).
Risperidone should not be used in
patients with dementia-related
psychosis.
NERVOUS SYSTEM
Altered cardiac conduction (life-threatening
arrhythmias have occurred; use caution
with history of cardiac abnormalities);
this may cause anticholinergic effects;
increased incidence of cerebrovascular
events, including stroke, in the elderly
with dementia-related psychosis; low
white cell count or previous blood
dyscrasias (may increase risk of
clinically significant dyscrasia).
EPS; neuroleptic malignant syndrome; tardive
dyskinesia; hyperglycemia and diabetes
mellitus (antipsychotics may increase
blood glucose); hyperprolactinemia.
Orthostatic hypotension; potential for cognitive
and motor impairment; dyslipidemia;
esophageal aspiration; disruption of
body temperature regulation;
Parkinson’s disease (risk of aggravation
and potential for drug interactions);
epilepsy (antipsychotics may alter EEG
or lower seizure threshold; use with
caution in people with, or at risk of,
seizures); hyperthyroidism (increases
risk of dystonia); risk factors for
prolonged QT interval (increase the risk
of arrhythmia and sudden death,
particularly when given IV); shock (drug-
related hypotension may worsen
symptoms); suicidal ideation; sedation;
weight gain; psychological and physical
dependence.
Pregnancy, refer to a specialist (avoid
antipsychotics if possible, or use the
lowest effective doses when
antipsychotic treatment is necessary);
breastfeeding (avoid its use if possible;
should not breastfeed during therapy or
for 12 weeks after the last injection).
Adverse Drug Reactions:
Common: Abdominal pain, akathisia, anxiety,
cough, dizziness, fatigue, fever,
headache, increased appetite,
insomnia, nausea, sedation, tremor,
vomiting, weight gain.
Less Common: Allergic reaction, anemia,
angioedema, AV block first-degree;
bradycardia, chest pain, EPS (other than
akathisia), hyperkinesia, hypertension,
hypotension, incontinence, palpitation,
peripheral edema, QT prolongation,
rash, rhinitis, sexual adverse effects,
somnolence, tachycardia.
Rare: Dyslipidemia, exacerbation of type 2 DM;
hepatotoxicity, stroke, TIA, tardive
dyskinesia, water intoxication due to
SIADH or polydipsia.
Drug Interactions:
NOTE: Risperidone is a substrate for CYP
enzymes (see Appendix); its
concentration may be affected by
various drugs, which act as enzyme
inducers or inhibitors.
Monitor closely with:
Acetylcholinesterase inhibitors (Central) –
these may enhance the central
neurotoxic effect of antipsychotics.
Antacids – there is decreased absorption when
these are given with risperidone within 1
to 2 hours.
Anticholinergics – risperidone may enhance
the adverse effect of other
anticholinergics.
Carbamazepine – this may decrease the
serum concentration of risperidone.
CNS depressants (e.g., alcohol, sedatives and
tranquilizers) – risperidone causes CNS
depression; administration with these
drugs may enhance its adverse effects
(e.g., sedation).
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, other
antipsychotics, calcineurin inhibitors,
high-dose thiazide diuretics and
somatropin) – risperidone can increase
blood glucose concentration, and may
increase risk of hyperglycemia if given
with these drugs.
Drugs which prolong QT interval (see Appendix
– Table B) – the QT interval may increase
if risperidone is given with these drugs;
increasing the risk of arrhythmias.
Drugs which reduce blood pressure (see
Appendix – Table D) – antipsychotics
can cause orthostatic hypotension and,
if given with these drugs, may have
enhanced hypotensive effects.
Loop diuretics – may enhance the adverse
effect of risperidone.
Avoid concomitant use with:
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NERVOUS SYSTEM
Dopamine agonists (e.g., cabergoline,
pergolide and levodopa) – antagonism;
risperidone can reduce their therapeutic
effect.
Seizure-inducing drugs (see Appendix – Table
C) – antipsychotics can possibly lower
seizure threshold; administration with
these drugs may increase the risk of
seizures.
Administration: Give long-acting IM deep into
either the deltoid or gluteal muscle;
avoid inadvertent injection into
vasculature. Injection should alternate
between the two arms or buttocks. Oral
dosage forms may be administered
without regard to meals.
Pregnancy Category: C
ATC Code: N05AX08
ANXIOLYTICS
DIAZEPAM
Rx
Oral: 5 mg tablet
Diazepam is a benzodiazepine that exerts
anxiolytic, sedative, muscle-relaxant,
anticonvulsant, and amnestic effects
due to its facilitation of the action of
gamma aminobutyric acid (GABA), an
inhibitory neurotransmitter in the central
nervous system.
Indications: Short-term management of anxiety
disorders, symptoms of anxiety, skeletal
muscle relaxant, acute agitation, tremor,
impending delirium tremens,
hallucinosis in acute alcohol withdrawal.
Contraindications: Known hypersensitivity to
diazepam or any of the excipients;
respiratory depression; marked
neuromuscular respiratory weakness,
including unstable myasthenia gravis;
acute pulmonary insufficiency; sleep
apnea syndrome; phobic or obsessional
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states; hyperkinesis; severe hepatic
impairment;
NOTE: Oral diazepam is not recommended for
chronic psychosis, this should not be
used alone in depression or in anxiety
with depression.
SKILLED TASKS. May impair ability to perform
skilled tasks, e.g., operating machinery
or driving.
Dose:
(See Precautions prior to administration)
Anxiety (symptoms/disorders), by mouth,
ADULT, 2 to 10 mg 2 to 4 times daily if
needed.
Skeletal muscle relaxant (adjunct therapy), by
mouth, ADULT, 2-10 mg 3 to 4 times
daily.
Dose Adjustments:
Elderly or Debilitated Patients:
Reduce dose.
Renal Impairment:
No dose adjustment recommended unless
used for prolonged periods; reduce dose
in prolonged periods.
Hepatic Impairment:
Reduce maintenance dose. Contraindicated in
severe liver disease.
Precautions:
WARNING: Overdose may produce coma
and respiratory depression.
Hepatic impairment and renal impairment (can
precipitate coma in cases of severe
hepatic and renal impairment); avoid
prolonged use and abrupt withdrawal.
Respiratory disease (compromised respiratory
drive in respiratory disease or sleep
apnea may lead to hypoventilation and
hypoxemia); muscle weakness may
worsen; history of alcohol or drug abuse,
marked personality disorder; use only if
the indication is clear, such as seizure
control; porphyria.
Pregnancy (high doses during late pregnancy
or labor may cause neonatal
hypothermia, hypotonia, and respiratory
depression); breastfeeding (adverse
effects are possible; monitor infant for
drowsiness);
NERVOUS SYSTEM
Adverse Drug Reactions: OTHER PSYCHOLEPTIC AGENTS
Common: Intravenous: Coma or sensorial
depression, hypotension, respiratory
depression. CARBAMAZEPINE
Rare: Allergic reactions, including anaphylaxis; Rx
jaundice, transient elevated liver
function tests.
Oral: 200 mg tablet
Drug Interactions: 200, and 400 mg MR (modified-release)
Monitor closely with: tablet
Amlodipine – enhanced hypotensive effect. 100 mg in 5 mL syrup, 120 ml
Azole derivatives (e.g., fluconazole) – these
may inhibit diazepam’s metabolism, It is an iminostilbene that limits the firing of
increasing the risk of adverse effects. action potentials evoked by a sustained
Chlorphenamine – enhanced sedative effect. depolarization in cortical neurons by
Chlorpromazine – enhanced sedative effect. slowing the rate of recovery of voltage-
CNS depressants (e.g., alcohol, sedatives and activated Na+ channels from
tranquilizers) – possibly enhanced CNS inactivation.
depression and sedative effect.
Enalapril – enhanced hypotensive effect. Indications: Second-line treatment of acute
Furosemide – enhanced hypotensive effect. mania and long-term mania.
Hydrochlorothiazide – enhanced hypotensive
effect. Contraindications: Hypersensitivity to
Methyldopa – enhanced hypotensive effect. carbamazepine or related drugs (e.g.,
Nitrates (e.g., isosorbide dinitrate) – enhanced tricyclic antidepressants), or any
hypotensive effect. component of the formulation;
Phenytoin – diazepam may possibly increase atrioventricular block; bone marrow
or decrease the concentration of this depression; acute intermittent
drug. porphyria; combination with
Seizure-inducing drugs (see Appendix – Table monoamine-oxidase inhibitors (MAOIs) –
C for other drugs which may also cause before administering carbamazepine,
seizures) – these may lower seizure MAOIs should be discontinued for 2
threshold when given concomitantly with weeks or longer (see Drug Interactions).
benzodiazepines.
Theophylline – these may reduce sedative Dose:
effects of benzodiazepines. NOTE: As a result of slow, controlled release of
the active substance from the CR
Avoid concomitant use with: tablets, these are designed to be taken
Isoniazid – metabolism of diazepam inhibited. in a twice-daily dosage regimen.
Rifampicin – this may substantially accelerate Acute mania/mixed mania, by mouth,
metabolism of diazepam, thus reducing ADULT/CHILD ≥13 years, start 200 mg
its concentration and clinical effect. daily (increase by 200 mg weekly to 400
– 600 mg daily in 2 divided doses,
Administration: Therapy with oral diazepam maximum of 1200 mg daily).
should replace parenteral
administration as soon as possible. Dose Adjustments:
Hepatic Impairment:
Pregnancy Category: D Metabolism is impaired in advanced liver
disease.
ATC Code: N05BA01 (drug is primarily metabolized in the liver).
Renal Impairment:

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NERVOUS SYSTEM
Use with caution; dose reduction in moderate
to severe impairment.
Elderly:
Dosage should be selected with caution.
Generally, lower dosages are started.
Precautions:
WARNING:
Hematologic: Agranulocytosis and aplastic
anemia have been reported (see below).
Neurologic: Must be used with caution in
patients with mixed seizures, including
absences, which can be exacerbated by
carbamazepine. In case of exacerbation,
the drug must be discontinued.
Transient or persistent decreased platelet or
white blood cell count can occur.
Agranulocytosis and aplastic anemia
have been associated but the overall risk
estimate is low. Obtain pre-treatment
Complete Blood Counts with platelet
counts at baseline and periodically
thereafter. Discontinue if there is
significant bone marrow depression.
If signs and symptoms of severe skin reaction
appear, carbamazepine should be
discontinued.
Baseline and periodic evaluations of hepatic
function must be performed particularly
in those with a history of liver disease
and the elderly. The drug must be
withdrawn immediately in cases of
aggravated liver dysfunction or active
liver disease.
The possibility of activation of latent psychosis
and, in the elderly, confusion and
agitation should be kept in mind.
Breakthrough bleeding may be seen in women
taking oral contraceptives. The reliability
of oral contraceptives may be adversely
affected by carbamazepine. Thus,
women of childbearing age must be
advised to use alternative forms of birth
control.
Pregnancy: the possibility that carbamazepine,
like all major antiepileptic drugs,
increases risk for developmental
disorders has been reported, with rare
reports of developmental disorders,
including spina bifida, with
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carbamazepine. Antiepileptic drugs can
aggravate folic acid deficiency so that
supplementation is recommended
before and during pregnancy. Vitamin
K1, to be given to the mother during the
last weeks of pregnancy as well as to the
newborn to prevent bleeding disorders in
the offspring has been recommended.
Lactation: carbamazepine passes into breast
milk so that infants must be closely
observed for adverse reactions.
SKILLED TASKS. Ability to react may be
impaired by dizziness and drowsiness
especially at the start of therapy or
during dose adjustments; patients must
exercise caution when driving or
operating machinery.
Adverse Drug Reactions:
NOTE: Particularly at the start of treatment, or
if the initial dose is too high, or in the
elderly, certain adverse reactions (e.g.,
central nervous system and
gastrointestinal symptoms, and allergy)
commonly occur.
Common: Neurologic: ataxia, dizziness,
drowsiness, fatigue, headache diplopia,
blurred vision; Skin: allergic reactions,
urticarial (may be severe); Blood:
leucopenia, thrombocytopenia,
eosinophilia; Liver: elevated gamma-GT
(usually not clinically relevant); elevated
alkaline phosphatase; Gastrointestinal:
nausea, vomiting, mouth dryness;
Endocrine/metabolism: edema, weight
increase, hyponatremia and reduced
plasma osmolality.
Less Common: Abnormal involuntary
movements, exfoliative dermatitis,
erythroderma, elevated transaminases,
diarrhea, constipation.
Rare: Orofacial dyskinesia, oculomotor
disorders, slurred speech, peripheral
neuritis, paresthesia, muscle weakness,
hallucinations, depression, loss of
appetite, restlessness, agitation,
confusion, lupus-erythematosus like
syndrome, pruritus, Stevens-Johnson
syndrome, acne, purpura, leukocytosis,
lymphadenopathy, folic acid deficiency,
delayed multiorgan hypersensitivity,
NERVOUS SYSTEM
hypertension or hypotension,
disturbance in cardiac conduction.
Very Rare (<0.01%): Agranulocytosis, aplastic
anemia, pure red cell aplasia,
megaloblastic anemia, pancreatitis,
anaphylactic reactions, arrhythmias,
renal or urinary dysfunction.
Drug Interactions:
Montor closely with:
Coadministration of inhibitors or inducers of
CYP 3A4, the main enzyme catalyzing
conversion of carbamazepine into the
10,11-epoxide (which is as
pharmacologically active as the parent
compound) may result in altered plasma
concentrations of carbamazepine and
either induce adverse reactions or
decrease carbamazepine plasma levels.
Agents that raise carbamazepine plasma
levels: isoniazid, diltiazem, fluoxetine,
macrolide antibiotics (e.g., erythromycin,
clarithromycin), azoles (e.g.,
fluconazole), loratadine, verapamil.
Agents that decrease carbamazepine plasma
levels: phenobarbitone, phenytoin,
theophylline, rifampicin, and possibly,
also clonazepam and valproic acid.
Clonazepam, valproic acid, alprazolam,
corticosteroids, digoxin, doxycycline,
felodipine, haloperidol, theophylline, oral
anticoagulants (warfarin), tricyclic anti-
depressants- plasma levels can be
lowered by carbamazepine.
Phenytoin- plasma levels of phenytoin can both
be raised or lowered by carbamazepine.
Paracetamol- combination with
carbamazepine may reduce
bioavailability of
paracetamol/acetaminophen.
Isoniazid- combination with carbamazepine
increases isoniazid-induced
hepatotoxicity.
Neuroleptics (e.g., haloperidol) – combination
with carbamazepine can increase
neurological adverse reactions even in
the presence of plasma therapeutic
level.
Diuretics (e.g., hydrochlorothiazide,
furosemide) – these may cause
symptomatic hyponatremia.
Valproic acid may, on the other hand, increase
levels of the active 10,11-epoxide
metabolite so dose adjustments have to
be made.
Avoid concomitant use with:
Monoamine-oxidase inhibitors (MAOIs) –
because they are structurally related to
tricyclic antidepressants,
carbamazepine is not recommended in
combination with MAOIs.
Oral contraceptives – their plasma levels can
be lowered, or their activity diminished
by carbamazepine (alternate
contraceptive methods must be
considered).
Administration: The tablets and the syrup (to
be shaken before use) may be taken
during, after, or between meals. Tablets
should be taken with little liquid. The CR
tablets should be swallowed unchewed
with a little liquid.
Pregnancy Category: D
ATC Code: N03AF01
VALPROIC ACID/
Rx VALPROATE
Oral: 200 mg/5 ml syrup valproic acid, 100
mL
250 mg and 500 mg divalproex sodium
tablet (sodium valproate and valproic
acid compound in a 1:1 molar
relationship) (immediate-release
tablet)
250 mg and 500 mg extended release
(ER) tablet
500 mg (333 mg sodium valproate +
145 mg valproic acid) controlled
release tablet
Valproate inhibits sustained repetitive firing of
cortical neurons by prolonging recovery
of voltage-activated Na+ channels from
inactivation.
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NERVOUS SYSTEM
Indications: First-line treatment for acute
mania (divalproex), mixed episodes
(divalproex, divalproex ER).
See Anticonvulsants for more information on
other indications of valproate.
Contraindications: Known hypersensitivity to
valproic acid or any component of the
formulation; hepatic disease or
significant hepatic dysfunction; urea
cycle disorders; hereditary
neurometabolic syndromes caused by
DNA mutations of the mitochondrial DNA
polymerase-gamma (POLG) gene (e.g.,
Alpers Huttenlocher Syndrome); active
pancreatitis.
Dose:
Acute mania, by mouth, ADULT, immediate
release: for less acute mania, initially
250-500 mg once daily on the first data
and slowly titrate dose based on efficacy
and tolerability. For more severe cases,
initially 750-1000 mg/day in divided
doses and increase dose rapidly to
desired clinical effect up to maximum of
60mg/kg/day. Due to half-life, the
immediate release formulation is ideally
dosed as twice daily, while the extended-
release formulation may be given once
daily with a corresponding dose increase
of about 8-20% when converting from
the immediate release formulation due
to decreased bioavailability compared to
the immediate release formulation,
controlled release: initially 25 mg/kg
once daily and increase dose rapidly to
desired clinical effect up to a maximum
of 60 mg/kg/day.
Start 500 mg daily (Increase slowly to 1000-
2000 mg daily, maximum of 60
mg/kg/day).
Precautions:
WARNING:
Hepatic failure resulting in fatalities has
occurred, usually during the first six
months of treatment. Increased risk for
fatal hepatotoxicity is seen in: children
<2 years old, patients on multiple
anticonvulsants, congenital metabolic
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disorders, severe seizure disorders
accompanied by mental retardation, or
organic brain disease, hereditary
neurometabolic syndromes (see
Contraindications). Patients and
caregivers must be instructed to monitor
for and immediately report non-specific
symptoms such as malaise, weakness,
lethargy, facial edema, anorexia, and
vomiting that may precede the
hepatotoxicity. Loss of seizure control
may also be seen. The drug must be
discontinued immediately in the
presence of suspected or apparent
significant hepatic dysfunction.
Pancreatitis, which may be life-threatening,
has been reported. Some were
hemorrhagic and progressed rapidly
from initial symptoms to death. Patients
and caregivers must be instructed to
monitor for and immediately report
symptoms of abdominal pain, nausea,
vomiting, and/or anorexia. The drug
should immediately be discontinued.
Teratogenicity: may cause neural tube defects.
Do not use in women of child-bearing age
unless the drug is essential.
Hepatotoxicity: see Contraindications and
Warning; Liver function tests (e.g.,
SGPT/ALT, prothrombin time) must be
done pre-treatment and periodically
especially within the first six months and
in patients most at risk.
Pancreatitis: see Warning; measure plasma
amylase immediately if with abdominal
pain.
Thrombocytopenia: Platelet counts and
coagulation tests, should be done before
treatment and periodically thereafter
particularly during the first six months of
therapy, and prior to surgery or
anticoagulant therapy.
Thrombocytopenia may be dose-related.
Evidence of hemorrhage, bruising, or
disordered coagulation are indications
for discontinuation.
An increase in the risk of suicidal thoughts and
behavior in patients taking antiepileptic
drugs (AEDs) has been reported.
Epilepsy and other illnesses for which
AEDs are prescribed can carry the same
NERVOUS SYSTEM
risk. Patients and their caregivers must
be instructed to monitor for and
immediately report any unusual change
in mood or behavior.
Pediatric Use: Children less than 2 years of age
are at increased risk for fatal
hepatotoxicity (see Warning). When used
in this age group, it should be done with
extreme caution and as a sole agent.
Pregnancy ! Valproic acid may cause
teratogenic effects, such as neural tube
defects (e.g., spina bifida). It must be
considered in women of child-bearing
age only after the risks have been
carefully weighed against the benefits.
Pregnant women on valproic acid must
be immediately referred to the specialist.
Urea cycle disorders: see Contraindications.
Hyperammonemic encephalopathy,
sometimes fatal, has been reported in
patients with these disorders.
SKILLED TASKS: ability to react may be
impaired by dizziness and drowsiness
especially at the start of therapy or
during dose adjustments; patients must
exercise caution when driving or
operating machinery.
Dose Adjustments:
Renal Impairment:
No adjustment necessary; protein-binding is
reduced.
Hepatic Impairment:
Avoid if possible, hepatotoxicity and hepatic
failure may occasionally occur, usually in
the first six months; avoid in active liver
disease.
Elderly:
Lower initial dose and slower increase in
dosage, regularly monitor fluid and
nutritional intake and increased
somnolence and other side effects.
Adverse Drug Reactions:
NOTE: The frequency of adverse effects,
particularly elevated liver enzymes and
thrombocytopenia, can be dose-related.
Common:
Gastrointestinal: Nausea, vomiting, abdominal
pain, diarrhea, anorexia, dyspepsia,
elevated AST/ALT (usually minor and
appear to be dose-related).
Neurologic: Somnolence, tremor, dizziness,
insomnia, nervousness, anxiety,
depression, amnesia, mood changes,
hallucinations, nystagmus, blurred
vision, amblyopia, ataxia, vertigo.
Hematologic: Thrombocytopenia, increased
bleeding time, petechiae/ecchymosis.
Respiratory: Flu syndrome, infection,
bronchitis, rhinitis, pharyngitis.
Others: Asthenia, headache, transient
alopecia, skin rash, increased appetite,
weight gain, tinnitus.
Less Common: Irregular menses, secondary
amenorrhea.
Rare: Hepatic failure (may be fatal),
pancreatitis, hyperammonemia,
Stevens-Johnson syndrome, toxic
epidermal necrolysis (see Warning and
Precautions).
Drug Interactions:
Monitor closely with:
Aspirin – this increase valproate free fraction
levels by plasma protein binding
competition.
Amitriptyline/Nortriptyline – its plasma
clearance is decreased with co-
administration of valproate. Consider
lowering dose of
amitriptyline/nortriptyline.
Carbamazepine – valproate may increase or
decrease carbamazepine levels.
Diazepam – valproate displaces diazepam
from binding sites and inhibits its
metabolism, increasing free fraction of
diazepam.
Phenobarbital – valproate inhibits its
metabolism; closely monitor for
neurologic toxicity, including CNS
depression.
Phenytoin – valproate displaces phenytoin
from binding sites and inhibits its
metabolism, increasing free fraction of
phenytoin.
Rifampin – increases oral clearance of
valproate; with need to adjust valproate
dosage.
Warfarin – in an in vitro study, valproate
increased unbound fraction of warfarin.
Its therapeutic relevance is unknown;
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NERVOUS SYSTEM
however, coagulation tests should be
monitored.
Avoid concomitant use with:
Carbapenem antibiotics (e.g., meropenem,
imipenem, ertapenem) – these decrease
valproate levels; can result in loss of
seizure control (alternative antibacterial
or anticonvulsant therapy should be
considered).
Administration:
Swallow tablets whole, do not chew or crush.
Taken preferably after food intake. If
dose is skipped, do not double the next
dose.
Pregnancy Category: D
ATC Code: N03AG01
ESCITALOPRAM
Rx
Oral: 10 mg tablet (as oxalate)
Escitalopram is a furancarbonitrile and S-
stereoisomer of citalopram. It induces
allosteric serotonin transporter (SERT)
inhibition which results in a significant
increase of serotonin.
Indications: Management of major depressive
disorder, generalized anxiety disorder.
Contraindications: Known QTc prolongation,
congenital long QTc syndrome.
Dose:
Generalized anxiety disorder, by mouth,
ADULT, initially 10 mg once daily. May
increase to 20 mg once daily if necessary.
Continue treatment for up to 12 months
after initial response.
Major depressive disorder, by mouth,
ADULT/CHILD> 12 years, initially 10 mg
once daily. May increase to 20 mg once
daily after at least 1 week (ADULT) or at
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least 3 weeks (CHILD>12 years) if
necessary. Continue treatment for at least
6 months to 1 year.
NOTE: For all indications, allow a sufficient
duration of therapy for around 4-8 weeks on
the maximum tolerable dose before
switching the antidepressant.
Dose Adjustments:
Geriatric:
10 mg once daily; use with caution as per the
Beers Criteria due to association of SSRIs
with falls and fractures in service
users/patients 65 years and older and
should be avoided such service
users/patients who have a history of falls or
fractures, as well as having the potential to
cause or exacerbate syndrome of
inappropriate antidiuretic hormone
secretion (SIADH) or hyponatremia monitor
sodium concentration closely when
initiating or adjusting the dose in older
adults.
Renal Impairment:
Use with caution
Hepatic Impairment:
Initially 5 mg once daily. Increase to 10 mg
once daily after 2 weeks
Precautions:
WARNING: Antidepressants increased the risk
of suicidal thinking and behavior
(suicidality) in children, adolescents, and
young adults with major depressive
disorder (MDD) and other psychiatric
disorders. Balance the risk with the clinical
need. Appropriately monitor patients of all
ages who are started on antidepressant
therapy and closely observe for clinical
worsening, suicidality, or unusual changes
in behavior. Advise families and caregivers
of the need for close observation and
communication with the health care
provider. Escitalopram is not approved for
NERVOUS SYSTEM
use in pediatric service/patients younger
than 12 years.
Electroconvulsive therapy (ECT): Use with
caution; no clinical studies have assessed
the combined use of escitalopram and
electroconvulsive therapy; may increase the
risks (e.g., cognitive adverse effects)
associated with electroconvulsive therapy;
consider discontinuing, when possible, prior
to ECT treatment.
Use with caution in patients with history of
seizures.
Use with caution in patients with bipolar
disorder unless treated with concomitant
mood stabilizing agent.
Monitor patients for activation of suicidal
ideation, especially children and
adolescents.
Do not use if patients are taking a MAO
inhibitor
Drug-induced
hypokalaemia/hypomagnesaemia
(malignant arrhythmias)
Concomitant administration or w/in 14
days of MAOIs withdrawal (serotonin
syndrome; fatal)
QTc prolonging agents e.g., pimozide
(additive effect; fatal; monitor)
Avoid concomitant use with:
Linezolid (may cause serotonin syndrome)
MAOIs (may cause serotonin syndrome)
Methylene blue (may cause serotonin
syndrome)
Pimozide (may precipitate torsades de pointes)
Administration: May be taken with or without
food
Pregnancy Category: Category C
ATC Code: N06AB10

STORAGE AND STABILITY: Store at 25°C.

Excursions permitted to 15-30°C. Protect
from light. FLUOXETINE
Rx
See General Precautions under Selective
Serotonin Reuptake Inhibitors in Chapter
Oral: 20 mg dispersible tablet/capsule
10: Nervous System for other precautions.
A selective serotonin reuptake inhibitor (SSRI)
Adverse Drug Reactions: that is less sedating, and has fewer
Common: Abnormal dreams, fatigue, anticholinergic and cardiotoxic effects
paresthesia, pyrexia, restlessness, than tricyclic antidepressants; it also has
sinusitis, yawning. longer half-life than the other SSRIs.
Less Common: Alopecia, bruxism, confusion,
epistaxis, menstrual disturbances, Indications: Moderate to severe depression;
mydriasis, edema, pruritus, syncope, anxiety disorders (e.g., panic disorder
tachycardia, taste disturbance, tinnitus. and obsessive-compulsive disorder).
Rare: Aggression, bradycardia,
Contraindications: Known hypersensitivity to
depersonalization.
fluoxetine or any of its components;
manic phase; patients receiving MAO
Drug Interactions: inhibitors currently or in the past two (2)
Monitor closely with: weeks (due to serotonin toxicity).
Tramadol, buspirone, tryptophan (serotonin
syndrome) Dose:
NSAIDs (bleeding) Depression, by mouth, ADULT, initially 20 mg
Oral anticoagulants (altered anticoagulant once daily, increased as necessary after
effects) 3-4 weeks to maximum of 60 mg daily

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NERVOUS SYSTEM
(40 mg daily in the elderly, but 60 mg
can be used); usual maintenance dose
in the range, 20-60 mg once daily (20-40
mg once daily in the elderly); CHILD, refer
to a specialist for management.
Obsessive-compulsive disorder, by mouth,
ADULT, >18 years, 20 mg daily;
increased gradually if necessary to a
maximum of 60 mg daily; ELDERLY,
usually maximum of 40 mg daily, but 60
mg can be used (review treatment if
response is inadequate after 10 weeks).
Panic disorder, by mouth, ADULT, 10 mg once
daily; do not exceed 20 mg daily.
NOTE: Consider the long duration of action of
fluoxetine when adjusting dosage.
Dose Adjustments:
Renal Impairment:
Use drug with caution for mild-to-moderate
renal impairment; for severe
impairment, the patient should be
referred to a specialist.
Hepatic Impairment:
For mild-to-moderate hepatic impairment, use
lower or less frequent dose; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: Antidepressants increase the risk of
suicidal thinking and behavior in
children, adolescents, and young adults
(18-24 years of age) with major
depressive disorder (MDD) and other
psychiatric disorders.
SSRIs should be used in caution in patients
with epilepsy (reduced seizure threshold;
avoid if poorly controlled, discontinue
use if convulsions develop).
Cardiac disease, may cause QT prolongation,
diabetes mellitus, susceptibility to angle-
closure glaucoma, a history of mania or
bleeding disorders (e.g., GI bleeding),
and if used with other drugs that
increase the risk of bleeding; people at
high risk of bleeding (age >80, or with
previous upper GI bleeding) or taking
drugs known to increase risk of GI
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bleeding, such as regular aspirin or
NSAIDs (likelihood of serious bleeding
may be increased; avoid combinations or
monitor clinical course carefully); renal
and hepatic impairment.
Bipolar disorder (all antidepressants may
provoke a manic episode when used in
patients with bipolar disorder).
Children and adolescents (increased risk of
suicide).
Avoid abrupt withdrawal (the dose should be
tapered over at least a few weeks).
Hyponatremia, mydriasis, hypoglycemia
reported.
Pregnancy (this should not be used unless the
potential benefit outweighs the risk;
increased risk of congenital heart
defects and neonatal withdrawal
symptoms); breastfeeding (present in
milk; avoid use).
SKILLED TASKS. May impair ability to perform
skilled tasks, for example operating
machinery or driving.
Adverse Drug Reactions:
Common: Agitation, anxiety, diarrhea,
dizziness, drowsiness, dry mouth,
headache, insomnia, myalgia, nausea,
rash, rhinitis, sexual dysfunction,
sweating, tremor, weakness, weight gain
or loss.
Less Common: Abnormal platelet aggregation
or hemorrhaging complication (e.g.,
bruising, epistaxis, GI and vaginal
bleeding), extrapyramidal symptoms
(including tardive dyskinesia,
tachycardia, hyponatremia (as part of
SIADH), hypotension, mydriasis.
Rare: Akathisia, blood dyscrasias, elevated
liver enzymes, galactorrhea, hepatic
failure, hepatitis, paresthesia, seizures,
taste disturbance.
Drug Interactions:
Monitor closely with:
Analgesics (Opioids) – these may enhance the
serotonergic effect of SSRIs (may cause
serotonin syndrome).
Agents with antiplatelet properties (NSAIDs) –
SSRIs may enhance the antiplatelet
effect of these drugs.
NERVOUS SYSTEM
CNS depressants (e.g., alcohol) – these may
enhance the adverse effect of SSRIs
(specifically, the risk of psychomotor
impairment may be enhanced).
Salicylates (e.g., aspirin) – their toxic effect
may be enhanced by the SSRIs;
increased risk of bleeding may result.
Vitamin K antagonists (e.g., warfarin) – their
anticoagulant effect may be enhanced
by the SSRIs.
Avoid concomitant use with:
Amiodarone – increased QTc interval.
Drugs which may contribute to serotonin
toxicity (e.g., MAO inhibitors) – may
increase likelihood of the said toxicity
(occasionally, the use of opioids which
do not usually affect serotonin
metabolism may result in serotonin
toxicity).
Seizure-inducing drugs (see Appendix – Table
C) – SSRIs can lower the seizure
threshold; administration with the said
drugs may decrease it further.
Tramadol – SSRIs may enhance the
neuroexcitatory and/or seizure-
potentiating effect of this drug.
Administration: Take this in the morning.
NOTE: Food reduces the incidence of the
common symptoms of nausea and
diarrhea associated with SSRI use.
Pregnancy Category: C
ATC Code: N06CA03
SERTRALINE
Rx
Oral: 50 mg tablet (as hydrochloride)
A selective serotonin reuptake inhibitor (SSRI)
that has pharmacokinetic parameters
similar to those of TCAs, and has short
half-life.
Indications: Treatment of major depression,
dysthymia and post-traumatic stress
disorder; obsessive-compulsive
disorder; panic disorder.
Contraindications: Known hypersensitivity to
sertraline or any component of the
formulation; should not be used if the
patient enters a manic phase; use of
MAO inhibitors to treat psychiatric
disorders (concurrently or within 14 days
of stopping sertraline or a MAO inhibitor).
Dose:
Depressive illness, by mouth, ADULT, initially
50 mg daily, increased if necessary by
increments of 25 to 50 mg at intervals of
at least 1 week to maximum of 200 mg
daily; (usual maintenance dose, 50 mg
daily).
Obsessive-compulsive disorder, by mouth,
ADULT, initially 50 mg daily, increased if
necessary in steps of 25 to 50 mg at
intervals of at least 1 week (maximum,
200 mg daily); CHILD, refer to a
specialist.
Panic disorder, post-traumatic stress disorder,
or social anxiety disorder, by mouth,
ADULT >18 years, initially 25 mg daily,
increased after 1 week to 50 mg daily; if
response is partial and if drug is
tolerated, increase the dose in steps of
25 to 50 mg at intervals of at least 1
week (maximum, 200 mg daily).
Dose Adjustments:
Renal Impairment:
Use with caution.
Hepatic Impairment:
Reduce dose or increase dose interval in mild
or moderate impairment;
Precautions:
WARNING: Antidepressants increase the risk of
suicidal thinking and behavior in
children, adolescents, and young adults
(18-24 years of age) with major
depressive disorder (MDD) and other
psychiatric disorders.
Possibility of a suicide attempt is inherent in
major depression and may persist until
remission occurs (prescriptions should
be written for the smallest quantity
consistent with good patient healthcare;
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NERVOUS SYSTEM
observe for clinical worsening and
suicidal ideation).
QTc prolongation; SSRIs should be used in
caution in patients with epilepsy
(reduced seizure threshold; avoid use if
poorly controlled or discontinue use if
convulsions develop); cardiac disease,
diabetes mellitus, susceptibility to angle-
closure glaucoma and a history of mania.
Bipolar disorder (all antidepressants may
provoke a manic episode when used in
patients with bipolar disorder); CNS
depression.
People at high risk of bleeding (age >80 or
previous upper GI bleeding), or taking
drugs known to increase risk of GI
bleeding, such as regular aspirin or
NSAIDs (likelihood of serious bleeding
may be increased); avoid combinations
or monitor clinical course carefully).
Children and adolescence (increased risk of
suicide).
Uric acid nephropathy.
Avoid abrupt withdrawal (the dose should be
tapered over at least a few weeks).
Hyponatremia and mydriasis reported.
Pregnancy, refer to a specialist (should not be
used unless potential benefit outweighs
the risk; increased risk of congenital
heart defects and neonatal withdrawal
symptoms); breastfeeding (present in
milk; avoid use if possible).
SKILLED TASKS. May impair ability to perform
skilled tasks, for example operating
machinery or driving.
Adverse Drug Reactions:
Common: Agitation, anxiety, chest pain,
constipation, diaphoresis, diarrhea,
dizziness, drowsiness, dryness of mouth,
dyspepsia, fatigue, headache,
hypesthesia, impotence, insomnia,
malaise, myalgia, nausea, nervousness,
palpitation, rash, rhinitis, sexual
dysfunction, somnolence, sweating,
tremor, weakness, weight gain or loss,
xerostomia.
Less Common: Abdominal pain, abnormal
platelet aggregation or hemorrhaging
complications (e.g., bruising, epistaxis,
GI and vaginal bleeding), EPS (including
Page | 292
tardive dyskinesia, tachycardia,
hyponatremia, hypotension, mydriasis).
Rare: Akathisia, allergic reaction including
Stevens-Johnson syndrome,
anaphylactoid reaction, angioedema,
atrial arrhythmia, AV block, blood
dyscrasias, bradycardia, diabetes
mellitus, elevated liver enzymes, hepatic
failure, hepatitis, hyperprolactinemia,
hypothyroidism, lupus-like syndrome,
neuroleptic malignant syndrome, optic
neuritis, pancreatitis, paresthesia,
photosensitivity, QT prolongation, renal
failure, seizure, serotonin syndrome,
SIADH, ventricular tachycardia.
Drug Interactions:
Monitor closely with:
Agents with antiplatelet properties (NSAIDs) –
SSRIs may enhance the antiplatelet
effect of these drugs.
Analgesics (Opioids) – these may enhance the
serotonergic effect of SSRIs (may cause
serotonin syndrome).
CNS depressants (e.g., alcohol) – these may
enhance the adverse effect of SSRIs
(specifically, the risk of psychomotor
impairment may be enhanced).
Hypoglycemic agents – SSRIs may enhance
their hypoglycemic effect (due to their
possibly increased concentration).
Salicylates (e.g., aspirin) – their toxic effect
may be enhanced by the SSRIs;
increased risk of bleeding may result.
Serotonin agonists and sympathomimetics –
increased risk of serotonin syndrome
when used with these drugs.
Thiazide diuretics – SSRIs may enhance their
hyponatremic effect.
Thyroid products – their therapeutic effect may
be diminished by SSRIs.
Vitamin K antagonists (e.g., warfarin) – their
anticoagulant effect may be enhanced
by the SSRIs.
Avoid concomitant use with:
Drugs which may contribute to serotonin
toxicity (e.g., MAO inhibitors) – may
increase likelihood of the said toxicity
(occasionally, the use of opioids which
do not usually affect serotonin
NERVOUS SYSTEM
metabolism may result in serotonin
toxicity).
Seizure-inducing drugs (see Appendix – Table
C) – SSRIs can lower the seizure
threshold; administration with the said
drugs may decrease it further.
Tramadol – SSRIs may enhance the
neuroexcitatory and/or seizure-
potentiating effect of this drug.
Tricyclic antidepressants – sertraline may
enhance the adverse effect of these
drugs (due to their possibly increased
serum concentration).
Administration: Administer once daily either in
the morning or evening; if somnolence is
noted, administer at bedtime.
NOTE: Food often reduces the incidence of the
common symptoms of nausea and
diarrhea associated with SSRI use.
Pregnancy Category: C
ATC Code: N06AB06
ANTIVERTIGO
BETAHISTINE
Rx
Oral: 8 mg and 16 mg tablet (as
hydrochloride/ dihydrochloride)
Betahistine is a partial agonist of histamine at
H1 receptors and antagonist at H3
receptors. It produces excitatory effects on
neuronal activity of cortical and subcortical
structures agonism and decrease vestibular
sensory input and increases release of
histamine from the hypothalamus via H3-
receptor antagonism.
Indications: Management of Ménière’s disease
Contraindications: Presence or history of active
peptic ulcer disease, pheochromocytoma
Dose:
Meniere’s disease (to decrease episodes of
vertigo), by mouth, ADULT, 8-16 mg thrice
daily or 24 mg twice daily. The usual dosage
range is 24-48 mg daily in divided doses.
Dose Adjustments:
Geriatric:
Use with caution due to likelihood of decreased
hepatic/renal function.
Renal Impairment:
Has not been studied; use with caution.
Hepatic Impairment:
Has not been studied, but betahistine
primarily undergoes hepatic
metabolism; use with caution.
Precautions:
Disease-related concerns:
Asthma; Cardiovascular disease
(ventricular extrasystoles, hypotension,
tachycardia); Hepatic impairment;
Peptic ulcer;
STORAGE AND STABILITY: Do not store
above 25°C. Store the tablets in the
original package.
Adverse Drug Reactions:
Common: headache, nausea, dyspepsia.
Rare: confusion, convulsions, drowsiness,
hallucination, paresthesia,
hypotension, tachycardia, ventricular
premature contractions, pruritus, skin
rash, Stevens-Johnson syndrome,
urticaria, abdominal distension,
abdominal pain, bloating, peptic ulcer,
vomiting, anaphylaxis, angioedema,
hypersensitivity reaction, dyspnea.
Drug Interactions:
Monitor closely with:
Reduces therapeutic effect of the following:
Beta-2 agonists e.g. Salbutamol
Reduces therapeutic effect of Betahistine:
Antihistamine [except Levocabastine]
Administration: Administer with or without
meals; administer with meals if adverse
Page | 293
NERVOUS SYSTEM
GI effects occur. Food intake slows
down absorption of betahistine.

Pregnancy Category: Not available

ATC Code: N07CA01

Page | 294
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
MEN, a single 2 g dose or 500 mg/day in
ANTIPARASITICS, 2 divided doses for 10 days.

INSECTICIDES AND Dose Adjustments:

REPELLENTS Renal Impairment:
Dose adjustment is not usually necessary.
However, consider reducing dose during
long-term therapy. For severe
ANTIPROTOZOALS impairment, the patient should be
referred to a specialist (as metabolites
may accumulate, possibly causing
AGENTS AGAINST AMOEBIASIS AND adverse effects).
OTHER PROTOZOAL AGENTS Hepatic impairment:
For severe liver disease, reduce total daily
dose to one-third or one-half, and give
once daily (risk of drug accumulation
METRONIDAZOLE
Rx and toxicity in severe impairment,
especially if renal impairment is also
present).
Oral: 250 mg and 500 mg tablet
Precautions:
125 mg base/mL (200 mg/5 mL (as
Treatment with disulfiram may cause psychotic
benzoate)) suspension, 60 mL
reactions; treatment with fluorouracil
(avoid combination); disulfiram-like
A nitroimidazole, antiprotozoal drug, which has
reaction with alcohol.
potent antibacterial activity against
Hepatic impairment and hepatic
anaerobes, including Bacteroides and
encephalopathy.
Clostridium spp.
Renal impairment; congestive heart failure;
history of blood dyscrasias; history of
Indications: For amoebiasis; giardiasis;
CNS disorders, and seizures
trichomoniasis. (For other indications,
(nitroimidazoles are neurotoxic and may
see under Metronidazole in the Section
aggravate existing neurological
on Anti-Infectives).
disease); clinical and laboratory
monitoring recommended in courses
Contraindications: Known hypersensitivity to
lasting longer than 10 days.
metronidazole or any component of the
Pregnancy (avoid use in early pregnancy; if this
formulation; chronic alcohol
is to be administered, avoid high-dose
dependence.
regimens; take in divided doses if
possible); breastfeeding (significant
Dose:
amounts in milk; may cause bitterness in
Amebiasis (Entamoeba histolytica), by mouth,
milk; use in divided doses if given after
CHILD, 35-50 mg/kg divided in 3 doses
breastfeeding rather than single daily
per day for 7-10 days. ADULT, 500 – 750
doses; avoid large doses; use an
mg 3 x a day for 7 – 10 days.
alternative drug if possible).
Giardiasis, by mouth, CHILD, 15 mg/kg divided
into 3 doses per day for 5-7 days. ADULT,
Adverse Drug Reactions:
15 mg/kg per day in 3 divided doses for
Common: Abdominal pain, anorexia, CNS
5-7 days, or 2 g once daily for 3 days,
effects (e.g., dizziness), constipation or
400 mg 3 x a day for 5 days, or 500 mg
diarrhea, GI disturbances, headache,
2 x a day for 7-10 days.
metallic taste, nausea, vomiting.
Urethritis and vaginitis due to Trichomonas, by
mouth, WOMEN, a single 2 g dose or 500
mg/day in 2 divided doses for 10 days;

Page | 295
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Less Common: Drowsiness, furry tongue (due
to growth of Candida), glossitis,
paresthesia, stomatitis.
Rare: Agranulocytosis, anaphylactic shock,
angioedema, aplastic anemia,
cholestatic hepatitis, C. difficile-
associated disease, darkening of urine,
seizures, hypersensitivity reactions,
jaundice, leukopenia (on prolonged or
high dosage regimens), myalgia, myopia,
optic neuritis, pancreatitis, peripheral
neuropathy, psychotic disorder, raised
liver enzyme, Stevens-Johnson
syndrome, thrombocytopenia, urethral
discomfort.
Drug Interactions:
Monitor closely with:
Contraceptives, Oral – their efficacy may be
reduced by metronidazole.
Phenobarbital – this may increase metabolism
of metronidazole, and reduce its
concentration with possible treatment
failure (monitor clinical effect as there
may be a need to increase its dose,
possibly by 2-3 times).
Avoid concomitant use with:
Alcohol – this results in a disulfiram-like
reaction (abdominal pain, flushing,
headache, nausea, vomiting,
tachycardia); (avoid alcoholic drinks
during, and for at least 24 hours after
treatment).
Administration: Tablets should be swallowed
whole with water, during or after a meal;
oral suspension should be taken one
hour before a meal or on an empty
stomach.
Pregnancy Category: B
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ANTI-MALARIALS
ARTEMETHER +
Rx LUMEFANTRINE (AL)
Oral: 20 mg artemether + 120 mg
lumefantrine tablet
A fixed-dose, antimalarial combination of an
oil-soluble, artemisinin analog and a
fluorene-derived aryl alcohol that is used
for uncomplicated P. falciparum malaria.
Indications: For acute, uncomplicated malaria
caused by P. falciparum, P. malariae, or
P. knowlesi, alone or with other
Plasmodium spp., in areas with
significant drug resistance; 2nd line drug
for treatment of uncomplicated P. vivax
or P. ovale infections.
Contraindications: Known hypersensitivity to
lumefantrine, halofantrine or
artemether, and other artemisinin
compounds; family history of sudden
death or congenital prolongation of QT
interval; history of arrhythmias, clinically-
relevant bradycardia, or CHF
accompanied by reduced left ventricular
ejection fraction; pregnancy (not for use
in the first trimester); breastfeeding
(discontinue breastfeeding during and
for 1 week after stopping treatment;
present in milk in animal studies).
Dose:
Uncomplicated malaria due to P. falciparum or
P. malariae (in combination with
primaquine tablet, 15 mg (0.24 mg base
per kg) on Day 1; 3 tablets per adult > 60
kg), by mouth.
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Day 1 Day Day kg and 1 tablet
2 3 INFANT after 8
ADULT 4 tablets 4 tablets 2 6-11 hours
and followed by times a day months
CHILD 4 tablets old
>35 kg after 8
hours
CHILD 25 3 tablets 3 tablets 2 Mixed malarial infection due to P. falciparum
to < 35 followed by times a day and P. vivax with or without P. malariae
kg 3 tablets (in combination with primaquine tablet
after 8 0.25 mg base per kg on Days 1 – 14), by
hours mouth.
CHILD 15 2 tablets 2 tablets 2
to < 25 followed by times a day Day 1 Day Day
kg 2 tablets 2 3
after 8 ADULT 4 tablets 4 tablets 2
hours followed by times a day
CHILD 5 1 tablet 1 tablet 2 4 tablets
to < 15 followed by times a day after 8
kg and 1 tablet hours
INFANT after 8 CHILD 25 3 tablets 3 tablets 2
6-11 hours to < 35 followed by times a day
months kg 3 tablets
old after 8
hours
CHILD 15 2 tablets 2 tablets 2
Uncomplicated malaria due to P. vivax or P. to < 25 followed by times a day
ovale (in combination with primaquine kg 2 tablets
tablet, 0.25 mg base per kg starting on after 8
Day 1), or, malaria due to P. knowlesi hours
(alone), plus primaquine tablet 0.25 mg CHILD 5 1 tablet 1 tablet 2
base per kg on Days 1 – 14 by mouth. to < 15 followed by times a day
kg 1 tablet
Day 1 Day Day after 8
2 3 hours
ADULT 4 tablets 4 tablets 2
followed by times a day
4 tablets NOTE: Refer to DOH Public Health Program on
after 8 Malaria for latest treatment guidelines.
hours
CHILD 25 3 tablets 3 tablets 2 Dose Adjustments:
to < 35 followed by times a day Renal and Hepatic Impairment:
kg 3 tablets Same dosage as in patients with normal
after 8 function may be used in patients with
hours mild-to-moderate impairment; for severe
CHILD 15 2 tablets 2 tablets 2 impairment, the patient should be
to < 25 followed by times a day referred to a specialist.
kg 2 tablets
after 8 Precautions:
hours Patients with cardiac conduction defects
CHILD 5 1 tablet 1 tablet 2 (including congenital QT prolongation,
to < 15 followed by times a day arrhythmias, or other conditions that

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ANTIPARASITICS, INSECTICIDES AND REPELLENTS
may prolong the QT interval);
concomitant administration of drugs that
prolong the QT interval; avoid in acute
porphyria, severe and/or complicated
malaria and first trimester of pregnancy;
electrolyte disturbances; monitor
patients unable to take food (greater risk
of recrudescence); severe renal and
hepatic impairment (monitor ECG and
plasma potassium concentration).
SKILLED TASKS. Dizziness may impair ability to
perform skilled tasks, e.g., operating
machinery or driving.
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, arthralgia,
asthenia, cough, diarrhea, dizziness,
fatigue, headache, itch, myalgia,
nausea, palpitations, prolonged QT
interval, pruritus, pyrexia, rash, sleep
disorder, vomiting, weakness.
Less Common: Ataxia, clonus, hypesthesia,
paresthesia.
Rare: Hepatitis, hypersensitivity reactions.
Drug Interactions:
Monitor closely with:
Drugs which prolong QT interval (see Appendix
– Table B) and other Antimalarials – QT
interval may be prolonged when given
concomitantly with this combination,
increasing the risk of arrhythmia.
Hormonal Contraceptives – their
effectiveness may be reduced by this
combination (use an additional method
of birth control).
Avoid concomitant use with:
CYP3A4 inducers (see Appendix) – can result
in decreased concentration of
artemether and/or lumefantrine, and
potential loss of anti-malarial efficacy.
Drugs metabolized by CYP2D6 (see Appendix)
– potential risk for QT prolongation.
Administration: Take the tablets with food or
high-fat meal to increase absorption. If
patient vomits out the dose within 1 to 2
hours, give another dose.
Pregnancy Category: C
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CHLOROQUINE
Rx
Oral: 250 mg (150 mg base) tablet (as
phosphate/ diphosphate)
An aminoquinoline antimalarial, which has
rapid schizontocidal activity against
blood forms of Plasmodium ovale and P.
malariae, and against susceptible
strains of P. vivax and P. falciparum. It
influences hemoglobin digestion by
increasing intravesicular pH in malaria
parasite cells and interferes with the
nucleoprotein synthesis of the patient.
Indications: Prophylaxis of malaria; treatment
of non-chloroquine resistant acute
malaria caused by P. malariae, P. vivax,
and P. ovale (followed in P. vivax and P.
ovale infections by primaquine to
eliminate intrahepatic forms).
Contraindications: Known hypersensitivity to 4-
aminoquinoline compounds (e.g.,
hydroxychloroquine and chloroquine) or
any component of the formulation; in
patients with history of epilepsy; retinal
damage or impaired visual field.
Dose:
NOTE: All doses are in terms of chloroquine
base.
Prophylaxis of malaria, by mouth, ADULT, 300
mg as base once weekly starting 1 week
before exposure continuing throughout
on a weekly basis and for at least 4
weeks after exposure; CHILD, 5 mg/kg
weekly.
Uncomplicated malariae due to P. vivax or P.
ovale, by mouth, ADULT, initially 600 mg
as base followed by 300 mg 6-8 hours
later in Day 1, then, single doses of 300
mg daily on Days 2-3; CHILD, initially 10
mg base/ kg (maximum: 600 mg base)
followed by 500 mg base/kg after 6
hours (max: 300 mg base ) then single
doses of 5 mg base/kg on Days 2 – 3.
Congenital and neonatal malaria, by mouth,
CHILD 10 mg /kg on Days 1 – 2, and 5
mg/ kg on Day 3.
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Relapse malaria, by mouth, ADULT and CHILD,
10 mg/kg on Days 1 – 2, and 5 mg/kg
on Day 3.
Mixed malarial infection due to P. vivax and P.
malariae, by mouth, ADULT and CHILD,
10 mg/kg on Days 1 – 2, and 5 mg/kg
on Day 3 (in combination with
primaquine 0.25 mg as base / kg per
day taken as a single dose for Days 1 –
14).
NOTE: Refer to DOH Public Health Program on
Malaria for latest treatment guidelines.
Dose Adjustment:
Renal Impairment:
For mild-to-moderate renal impairment, dose
reduction is warranted; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
G6PD deficiency (potential risk of hemolysis);
Porphyria cutanea tarda (treating this
condition with higher doses of
chloroquine has caused hepatotoxicity);
psoriasis may be worsened; epilepsy
(tonic-clonic seizures have been
reported); risk factors for prolonged QT
interval (may prolong QT interval and
increase the risk of arrhythmias); may
aggravate myasthenia gravis;
neurological disorders; renal
impairment; hepatic impairment (avoid
concurrent therapy with hepatotoxic
drugs); severe GI disorders.
Pregnancy (in the first trimester of pregnancy,
quinine in combination with clindamycin
for 7 days is the treatment of choice –
this combination can be used
throughout pregnancy; in acute malaria
and third trimester: benefit of
prophylaxis and treatment outweighs
risk).
NOTE: If clindamycin is not available, then
quinine should be given as
monotherapy.
Breastfeeding (at doses used for malaria
prophylaxis; amount in milk is probably
too small to be harmful, and inadequate
for reliable protection against malaria in
the breastfed infant; avoid breastfeeding
when used for rheumatic disease).
NOTE: If patient continues to deteriorate after
chloroquine medication – suspect
resistance and administer quinine IV as
emergency measure.
Adverse Drug Reactions:
Common: GI disturbances, itch, lack of
appetite, pruritus, skin eruptions, weight
loss.
Less Common: Anxiety, confusion, dizziness,
drowsiness, headache, hypotension,
irreversible retinopathy, paresthesia,
personality changes, psychotic episodes,
reversible corneal opacities, sleep
disorders, vertigo, visual disturbances.
Rare: Agranulocytosis, arrhythmias, bleaching
of hair, blood dyscrasias, blue-black
pigmentation of mucous membranes
and skin, bone marrow suppression,
convulsions, hair loss, hearing loss,
hypersensitivity reactions, pancytopenia,
porphyria, prolonged QT interval,
psoriasis, neuromyopathy, seizure, rash,
Stevens-Johnson syndrome,
thrombocytopenia, tinnitus, toxic
epidermal necrolysis.
Drug Interactions:
NOTE: Chloroquine has a long half-life;
consequently, the potential for drug
interactions may persist for weeks after
it has been stopped.
Monitor closely with:
Antacids (e.g., aluminum or magnesium
hydroxide) – these may reduce the
absorption of chloroquine.
Digoxin – the serum levels of digoxin may be
increased by chloroquine.
Praziquantel – its metabolism may be
increased by chloroquine, reducing its
concentration and therapeutic effects
(increase the dose if necessary).
Avoid concomitant use with:
Artemether + Lumefantrine – these may result
to potentially hazardous interactions
when given concomitantly with
chloroquine.
Drugs which prolong QT interval (see Appendix
–Table B) and other Antimalarials – QT
interval may be prolonged when given
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ANTIPARASITICS, INSECTICIDES AND REPELLENTS
concomitantly with chloroquine,
increasing the risk of arrhythmia.
Administration: To avoid nausea and vomiting,
tablets should be administered after
meals.
NOTE: If part or all of a dose is vomited, same
amount should immediately be
readministered.
Pregnancy Category: C
PRIMAQUINE
Rx
Oral: 26.3 mg (15 mg base) tablet (as
diphosphate)
An aminoquinoline antimalarial used for the
radical cure and terminal prophylaxis of
infections with P. vivax and P. ovale.
Indications: Radical cure in relapsing
infections of P. vivax and P. ovale
malaria; elimination of intrahepatic
forms of P. vivax and P. ovale (after
standard chloroquine therapy);
elimination of P. falciparum gametocytes
(after standard therapy with a blood
schizontocide).
Contraindications: Known hypersensitivity to
primaquine or any component of the
formulation; G6PD deficiency in infants
(risk of hemolysis); infants <1 year
(methemoglobinemia); patients with
conditions that predispose to
granulocytopenia (including active
rheumatoid arthritis and systemic lupus
erythematosus); pregnancy (treatment
with primaquine should be delayed until
after delivery; third trimester: neonatal
hemolysis and methemoglobinemia),
and breastfeeding.
Dose:
NOTE: All doses are in terms of primaquine
base.
Uncomplicated malaria due to P. falciparum or
P. malariae in combination with
Page | 300
artemether-lumefantrine), by mouth,
ADULT and CHILD, 0.25 mg base per kg
per day as a single dose per day 1.
Uncomplicated malaria due to P. vivax or P.
ovale, first-line treatment (in
combination with chloroquine 10 mg/kg
on Days 1 - 2, then, 5 mg/kg on Day 3),
by mouth, ADULT and CHILD, 0.25 mg
base/kg per day as a single dose for
Days 1 – 14.
Relapse malaria due to hypnozoites of P. vivax
(in combination with chloroquine 10
mg/kg on Days 1 – 2, then, 5 mg/kg on
Day 3; or, with artemether-lumefantrine),
by mouth, ADULT and CHILD, 0.75
mg/kg per day on Days 1 – 14
(maximum dose: 30-45 mg/day).
Severe malaria due to P. vivax or P. ovale (in
combination with artemether-
lumefantrine).
Mixed malarial infection due to P. falciparum
and P. vivax with or without P. malariae
(in combination with artemether-
lumefantrine).
Mixed malarial infection due to P. vivax and P.
malariae (in combination with
chloroquine tablet 10 mg/kg on Days 1
– 2, then, 5 mg / kg on Day 3), by mouth,
ADULT and CHILD, 0.25 mg base /kg per
day as a single dose for Days 1 – 14.
Relapse malaria due to P. vivax (in combination
with chloroquine 150 mg base tablet, 2
tablets weekly for 8 weeks), by mouth,
ADULT (lactating women), 0.25 mg/kg
daily on Days 1 – 14 (maximum: 30-35
mg daily).
NOTE: Refer to DOH Public Health Program on
Malaria for latest treatment guidelines.
Dose Adjustment:
Renal Impairment:
Same dosage as in patients with normal
function may be used in patients with
mild-to-moderate renal impairment; for
severe impairment, the patient should
be referred to a specialist.
Precautions:
G6PD deficiency (exclude before radical
treatment for P. vivax and P. ovale
malaria; but this is not necessary before
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
single-dose gametocytocidal treatment); Indications: Prophylaxis and treatment
for patients receiving other potentially (supplement to quinine or artesunate) of
hemolytic drugs that depress myeloid multidrug-resistant P. falciparum
elements of the bone marrow (monitor malaria.
blood count: if either
methemoglobinemia or hemolysis Contraindications: See under Antimicrobial
occurs, withdraw treatment and consult (Oral and Parenteral).
a physician).
Dose:
2nd line treatment of uncomplicated malaria
Adverse Drug Reactions: due to P. falciparum or P. malariae,
Common: Abdominal pain, anorexia, dizziness, second-line treatment (in combination
headache, leukocytosis, nausea, with quinine sulfate, 10 mg/kg every 8
vomiting. hours for 7 days and primaquine tablet,
Less Common: Hemolytic anemia, 15 mg (0.24 mg base per kg on day 1);
methemoglobinemia. 3 tablets for adults > 60 kg), by mouth,
Rare: Agranulocytosis, anemia, arrhythmias, ADULT, 100 mg 2 x a day for 7 days.
granulocytopenia, hemoglobinuria, Prophylaxis of chloroquine-resistant malaria,
hypertension, interference with visual beginning 1-2 days before travel to
accommodation, leukopenia, pruritus. malarious area up to 4 weeks after
leaving, by mouth, ADULT, 100 mg daily;
Drug Interactions: CHILD > 8 years old, 2.2 mg base/kg
Monitor closely with: daily.
Chloroquine – its metabolism may be inhibited Chloroquine-resistant falciparum malaria,
by primaquine. acute attack, by mouth, ADULT, 200 mg
Avoid concomitant use with: daily for at least 7 days, with or after
Artemether + Lumefantrine – these may result treatment with quinine.
to potentially hazardous interactions
when given concomitantly with NOTE: Refer to DOH Public Health Program on
primaquine. Malaria for latest treatment guidelines.

Administration: Take with food to avoid Administration:

stomach upset and pain. Capsules should be swallowed whole with
plenty of water (a full glass of water).
Pregnancy Category: C Remain sitting or standing for at least 30
minutes to prevent esophageal irritation
or damage.
OTHER ANTI-MALARIALS May be given with food to counter gastric
irritation. Do NOT give with milk.

DOXYCYCLINE See under section on Anti-infectives for

Rx Systemic Use for other information.

Pregnancy Category: D
Oral: 100 mg capsule (as hyclate)
ATC Code: JO1AA02
A broad-spectrum and long-acting tetracycline
antibiotic used for infections caused by
chlamydia, spirochetes and other
pathogens, and for malarial prophylaxis.

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ANTIPARASITICS, INSECTICIDES AND REPELLENTS
ANTIHELMINTICS
PRAZIQUANTEL
Rx
Oral: 600 mg tablet
A quinoline-derived, broad-spectrum
anthelmintic, which is effective, as a
single dose, in the treatment of
schistosome infections of all species,
and other trematode and cestode
infections, including cysticercosis.
Indications: Intestinal schistosomiasis; urinary
schistosomiasis; intestinal, liver, and
lung fluke infections; cestode infections.
Contraindications: Known hypersensitivity to
praziquantel or any component of the
formulation; ocular cysticercosis.
Dose:
Intestinal fluke infections, by mouth, ADULT
and CHILD > 4 years, 25 mg/kg as a
single dose.
Liver and lung fluke infections, by mouth,
ADULT and CHILD >4 years, 25 mg/kg 3
times daily for 2 consecutive days;
alternatively, 40 mg/kg as a single dose;
treatment may need to be extended for
several days in paragonimiasis.
Schistosomiasis, by mouth, ADULT and CHILD
>4 years, 40-60 mg/kg as a single dose;
or in 3 divided doses of 20 mg/kg at
intervals of 4-6 hours.
Dose Adjustment:
Hepatic Impairment:
Consider reducing dose due to increased
concentration and half-life.
Precautions:
Cardiovascular disease; cerebral cysticercosis
(it is recommended to hospitalize
patients for the duration of treatment);
Ocular cysticercosis (severe eye damage
due to death of parasites may occur); in
undiagnosed neurocysticercosis
Page | 302
(seizures may result if praziquantel is
used to treat another systemic
infection); Paragonimus infections
(treatment in hospital as there may be
CNS involvement); patients with severe
hepatic disease; areas endemic for
cysticercosis (possible risk of
edematous reaction); reduced liver drug
metabolism may result in higher and
longer lasting plasma concentration of
unmetabolized praziquantel.
Pregnancy (Taenia solium infections should be
treated immediately; benefit of
treatment in schistosomiasis outweighs
the risk; if treatment is not considered
essential, it should be delayed until after
delivery); breastfeeding (there is low
excretion in breast milk; avoid
breastfeeding during, and for 72 hours,
after treatment; considered safe to
continue breastfeeding during treatment
for schistosomiasis).
SKILLED TASKS. May impair ability to perform
skilled tasks, e.g., operating machinery
or driving (warn patient not to operate
machinery nor drive during treatment or
for 24 hours after treatment).
Adverse Drug Reactions:
Common: Abdominal pain, anorexia, appetite
loss, colic, diarrhea, dizziness,
drowsiness, fever, headache, malaise,
myalgia, nausea, reversible rises in
aminotransferases (hepatic),
somnolence, urticaria, vertigo, vomiting.
Rare: Arrhythmias, bloody diarrhea,
hypersensitivity reactions (e.g., fever,
pruritus), rectal bleeding, seizures.
Drug Interactions:
Monitor closely with:
Albendazole – increased plasma concentration
of active metabolite of albendazole.
Carbamazepine – this increases metabolism of
praziquantel, reducing its concentration
and therapeutic effect
Chloroquine – this may increase metabolism of
praziquantel, reducing its concentration
and therapeutic effect.
Dexamethasone – this may increase
metabolism of praziquantel, reducing its
concentration and therapeutic effect.
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Phenytoin – this increases metabolism of
praziquantel, reducing its concentration
and therapeutic effect.
Avoid concomitant use with:
Strong CYP450 inducers (e.g., rifampicin) –
these increase metabolism of
praziquantel, reducing its plasma
concentration to ineffective levels.
Administration: Swallow it with water, without
chewing, to lessen its bitter taste.
Pregnancy Category: B
ALBENDAZOLE
Rx
Oral: 400 mg chewable tablet
200 mg/5 mL suspension, 10 mL and
60 mL
A benzimidazole-derived, broad-spectrum, oral
anthelmintic, which is used for long-term
treatment of tissue helminth infections,
including hydatid disease and
cysticercosis.
Indications: Filariasis; nematode infections,
including ascariasis, capillariasis,
enterobiasis, hookworm infections,
strongyloidiasis, trichostrongyliasis,
trichuriasis.
Contraindications: Known hypersensitivity to
albendazole or any component of the
formulation; pregnancy (first trimester:
avoid in nematode infections); hepatic
cirrhosis; cestode infections due to
Taenia solium occurring during
pregnancy; ocular cysticercosis (severe
eye damage due to death of parasites
may occur).
Dose:
Filariasis (selective treatment for patient
positive for microfilariae in nocturnal
blood examination, 12 days treatment),
by mouth, ADULT, as follows:
Day 1: 400 mg albendazole and 6 mg/kg
body weight of diethylcarbamazine
citrate (DEC) in 3 divided doses;
Day 2 to Day 12: 6 mg/kg body weight of
DEC only, given in 3 divided doses daily.
NOTE: Refer to DOH National Filariasis
Elimination Program for more details.
Intestinal helminths, by mouth, ADULT and
CHILD > 2 years old, 400 mg as single
dose.
Dose Adjustment:
Hepatic Impairment:
Consider dose reduction during extended
treatment.
Precautions:
Liver disease (patients may be more at risk for
adverse effects); liver function tests,
clinical signs of hepatic toxicity and
blood count should be monitored before
a longer-term treatment (twice during
each cycle).
Exclude pregnancy before starting the
treatment (advise patients to use non-
hormonal contraception during and for
one month after treatment);
breastfeeding.
Adverse Drug Reactions:
Common: Abdominal pain, headache, nausea,
vomiting.
Less Common: Abnormal liver function tests,
diarrhea, dizziness, fever, increased
intracranial pressure, meningeal signs,
vertigo.
Rare: Agranulocytosis, allergic shock (if with
cyst leakage), aplastic anemia, bone
marrow suppression, jaundice,
convulsions, erythema multiforme,
hepatitis, hypersensitivity reactions,
proteinuria, Stevens-Johnson syndrome.
Drug Interactions:
Monitor closely with:
Phenobarbital – this may increase the
metabolism of albendazole, decreasing
its concentration and possibly its
efficacy.
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ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Phenytoin – this may increase the metabolism
of albendazole, decreasing its
concentration and possibly its efficacy.
Praziquantel – this may increase plasma
concentration levels of the active
metabolite of albendazole.
Administration: Taken with food; oral
absorption may be increased 4-5 times
with fatty meal.
Pregnancy Category: C
DIETHYLCARBAMAZINE
Rx
Oral: 50 mg tablet (as citrate)
A piperazine-derived, filarial medicine, which
renders microfilariae susceptible to
destruction by the host’s defense
mechanism through parasite
immobilization, normal habitat
dislocation and surface membrane
alteration.
Indication: Management of filariasis.
Contraindications: Known hypersensitivity to
diethylcarbamazine or any component of
the formulation; pregnancy (delay
medication until after delivery).
Dose:
Filariasis (selective treatment for patients
positive for microfilariae in nocturnal
blood examination, 12 days treatment),
by mouth, ADULT, as follows:
Day 1: 6 mg/kg body weight diethyl-
carbamazine citrate (DEC) in 3 divided
doses, and albendazole, 400 mg;
Day 2: 6 mg/kg body weight of DEC only,
given in 3 divided doses daily.
PATIENT ADVICE. Complete the prescribed
course as directed to minimize allergic
reactions to dying parasites.
Dose Adjustment:
Renal Impairment:
Page | 304
Consider reducing dose since plasma half-life
is prolonged, and urinary excretion is
considerably reduced.
Precautions:
Cardiac disorders; other severe acute diseases
(delay treatment until after recovery);
treatment should be well-supervised
since allergic reaction is common and
usually severe (especially in
onchocerciasis and loiasis); monitor for
eye changes (reactions may be modified
by concomitant steroid administration).
Adverse Drug Reactions:
Common: Allergic reactions.
Less Common: Anorexia, asthmatic attacks,
dizziness, drowsiness, fever, headache,
joint pain, malaise, transient hematuria,
urticaria, vomiting.
Rare: Convulsions, exacerbation of
lymphedema, transient lymphangitis.
Drug Interactions: No information found.
Administration: Tablets should be taken after
meals; total cumulative dose of 72
mg/kg for W. bancrofti infections; best
initiated with smaller doses for 2-3 days
to avoid potential risk of immunological
reactions; rigorous hygiene is essential.
PATIENT ADVICE. Complete the prescribed
course as directed to minimize allergic
reactions to dying parasites.
Pregnancy Category: X
ATC Code: P02CB02
MEBENDAZOLE
Rx
Oral: 100 mg tablet/ capsule
500 mg tablet/ chewable tablet
A benzimidazole derivative that inhibits the
formation of helminth microtubules. It
selectively and reversible blocks glucose
uptake and other nutrients in
ANTIPARASITICS, INSECTICIDES AND REPELLENTS
susceptible adult intestine-swelling
helminths. ECTOPARASITICIDES,
INCLUDING SCABICIDES,
Indication: Management of common
roundworm infestation.
INSECTICIDES AND
REPELLENTS
Dose:
Ascaris lumbricoides (roundworm),
Strongyloides stercoralis (roundworm),
PERMETHRIN
mixed infection, by mouth, ADULT,
ADOLESCENT and CHILD > 2 years old,
Rx
500 mg as single dose, or 100 mg twice
daily for 3 days, repeat in 3 weeks if not Lotion:1%, 125 mL bottle
cured with initial treatment. 5%, 30 mL and 60 mL bottle
Pregnancy, use with caution: consider Shampoo: 1%, 30 mL and 60 mL bottle
postponing therapy until the third
trimester of pregnancy. A pyrethroid having similar chemical properties
with the natural insecticide pyrethrin, but
Adverse Drug Reactions:
remains as an effective scabicide for
Dizziness, drowsiness, headaches, seizure, longer periods of time.
alopecia, angioedema, exanthem,
itching, rash, Stevens Johnson Indications: Head lice (Pediculus humanus
Syndrome, Toxic Epidermal Necrolysis, capitis) and body lice (Pediculus
urticaria, abdominal pain, diarrhea, humanus corporis); scabies.
vomiting, agranulocytosis, eosinophilia,
decreased hemoglobin, leucopenia, Contraindications: Known hypersensitivity to
neutropenia, hepatitis, hematuria, permethrin or any component of the
glomerulonephritis, hypersensitivity formulation; hypersensitivity to plants
reactions. from Asteraceae Family (ragweed);
pregnancy.
Drug Interactions:
Avoid concomitant use with metronidazole Dose:
(increased risk of adverse or toxic side Body lice, ADULT and CHILD, apply lotion over
effects such as Stevens-Johnson whole body and wash off after 8-12
Syndrome or Toxic Epidermal hours; if hands are washed with soap
Necrolysis). within 8 hours of application, treat the
hands again; repeat application after 7
Administration: May be administered with or
days.
without food. Tablets may be chewed, Head lice, ADULT and CHILD, apply 1%
swallowed whole, or crushed and mixed shampoo undiluted to affected areas for
with food. 10 minutes and then rinse off with warm
water.
Pregnancy Category: C Scabies, ADULT and CHILD, apply 5% lotion
once from the chin and neck down the
ATC Code: PO2CA01 affected area to the toes and fingernails
and toenails. May require 30 g. Leave on
the area for 8-14 hours then wash off.
Repeat in 1-2 weeks. Reapply to hands
after handwashing. Treat close contacts.
Wash and dry linens to prevent re-
infection.

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ANTIPARASITICS, INSECTICIDES AND REPELLENTS
Precautions:
Should not be used on inflamed or broken skin;
avoid contact with the eyes; not for use
in infants <2 years old; breastfeeding
(withhold during treatment).

Adverse Drug Reactions:

Common: Local irritation, mild burning,
pruritus.
Less Common: Erythema, numbness, stinging,
tingling.
Rare: Cross-sensitization to pyrethrins or
chrysanthemum, edema, rash.

Drug Interactions: No information found.

Administration: Apply the lotion or shampoo to

towel-dried hair until hair and scalp are
saturated, especially behind the ears
and on the nape of the neck. Leave on
hair for 10 minutes and rinse with warm
water.

Pregnancy Category: B

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RESPIRATORY SYSTEM
acidosis, hypernatremia and renal
function impairment.
RESPIRATORY SYSTEM
Adverse Drug Reactions:
Rare: Hypersensitivity reactions, local irritation
of the skin and mucous membranes.
THROAT PREPARATIONS
Drug Interactions:
Monitor closely with:
Products that are incompatible with povidone-
iodine: Bupivacaine (Liposomal) [allow
POVIDINE-IODINE the site to dry completely before
Rx administering bupivacaine].

Avoid concomitant use with:

Oral Antiseptic: 1%, 60 mL and 120 mL bottle Products that are incompatible with povidone-
iodine: Benzalkonium Chloride,
An iodophore with a powerful broad-spectrum Collagenase.
germicidal activity against a wide range
of bacteria, viruses, fungi, protozoa and TEST INTERACTIONS. May interfere with thyroid
spores. function test results and interpretation if
used for prolonged periods.
Indications: : oral hygiene; oral candidiasis.
Administration: Do NOT ingest. Ensure to spit
Contraindications: prolonged use in patients out the solution after thorough rinsing.
with thyroid disorders or on lithium May color teeth and mucous
therapy; premature neonates or membranes.
neonates weighing
Pregnancy Category: D
Dose:
Oral hygiene, by mouth, ADULT and CHILD >6 ATC Code: R02AA15
years, gargle with 10 mL 0.1% solution,
undiluted or diluted with an equal
amount of warm water for 30 seconds 4
times daily for 14 days. DRUGS FOR OBSTRUCTIVE
Oral candidiasis, by mouth, ADULT, gargle
using the 1% solution.
AIRWAY DISEASE

Precautions:
EPINEPHRINE
May interfere with thyroid function tests (due Rx (ADRENALINE)
to systemic effects); broken skin (see
notes below); renal impairment (avoid
regular application to inflamed or broken Inj.: 1 mg/mL (as hydrochloride), 1 mL ampule
mucosa). (IM, SC)
Pregnancy (second and third trimesters:
sufficient iodine may be absorbed to A direct-acting, mixed alpha- and beta-
affect the fetal thyroid). adrenoceptor agonist; a
Avoid contact with eyes; lactation; neonates. sympathomimetic catecholamine, which
NOTE: Large open wounds: the application of is a potent cardiac stimulant
povidone-iodine to large wounds or vasoconstrictor and bronchodilator.
severe burns may produce systemic
adverse effects, such as metabolic

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RESPIRATORY SYSTEM
NOTE: Vasodilator at low dose (beta2
receptors);
but, vasoconstrictor at high dose (alpha
receptors).
Indications: For severe angioedema with
laryngeal swelling or airway obstruction;
anaphylactic shock; may be used in
cases of serious and fatal anaphylaxis.
Contraindications: Pheochromocytoma; use in
local anesthesia of fingers, toes, ears,
nose or genitalia; shock; organic heart
disease or cardiac dilatation; closed-
angle glaucoma; labor.
NOTE: There are no absolute contraindications
to
the use of epinephrine in life-threatening
allergic reactions.
Dose:
Severe angioedema with laryngeal swelling or
airway obstruction, by IM or SC
administration, ADULT, 0.3 mg.
Anaphylaxis, by IM or SC injection of 1:1,000
epinephrine injection, ADULT and
ADOLESCENT, 500 micrograms (0.5
mL); CHILD 6-12 years, 250 micrograms
(0.25 mL); CHILD 6 months-6 years, 120
micrograms (0.12 mL); INFANT <6
months, 50 micrograms (0.05 mL); by
SC injection of 1:1,000 epinephrine
injection, CHILD, 10 micrograms/kg
(0.01 mL/kg) bodyweight, repeat if
necessary at intervals of 20 minutes to 4
hours depending on the response of the
patient and the severity of the condition
(maximum single dose, 500
micrograms).
Administration:
Epinephrine is best administered as an SC or
IM injection into the anterolateral
aspect of the middle third of the thigh
for anaphylaxis, and by IV injection for
cardiac arrest or emergency situations.
NOTE: Do NOT mix with alkaline solutions.
Discard after 24 hours or if solution is
discolored or contains precipitate.
Page | 308
See Epinephrine (Adrenaline) under Cardiac
Therapy – Cardiac Stimulants, excluding
Cardiac Glycosides in Cardiovascular
System for other information.
Pregnancy Category: C
ATC Code: C01CA24
FLUTICASONE +
Rx SALMETEROL
Inhalation:
DPI:
100 micrograms fluticasone (as propionate) +
50 micrograms salmeterol (as xinafoate) x
28 doses and 60 doses with appropriate
accompanying dispenser
250 micrograms fluticasone (as propionate) +
50 micrograms salmeterol (as xinafoate) x
28 doses and 60 doses with appropriate
accompanying dispenser
500 micrograms fluticasone (as propionate) +
50 micrograms salmeterol (as xinafoate) x
28 doses and 60 doses with appropriate
accompanying dispenser
A combination product containing an inhaled
corticosteroid, and a long-acting beta2-
adrenoceptor agonist, which is used for
controlling the symptoms of asthma.
Indications: For asthma in patients aged 4
years and older; maintenance treatment
of airflow obstruction, and reduction of
exacerbations in patients with COPD.
NOTE: This is not indicated for the relief of
acute bronchospasm; this should be
used only if the asthma is deemed to be
not well-controlled with a long-term
asthma control medicine (e.g., inhaled
corticosteroids).
Contraindications: Primary treatment of status
asthmaticus or acute episodes of
asthma requiring intensive measures;
hypersensitivity to milk proteins, or any
component of the formulation.
RESPIRATORY SYSTEM
Dose:
Treatment of asthma, by inhalation, ADULT
and CHILD ≥12 years, 1 inhalation
(100/50 to 250/50) twice daily (starting
dose is based on asthma severity);
CHILD 4 to 11 years, 1 inhalation
100/50 twice daily.
Maintenance treatment of COPD, 1 inhalation
250/50 twice daily.
Dose Adjustment:
Renal Impairment:
Use with caution, but no adjustments
necessary.
Precautions:
Deterioration of disease and acute episodes:
do not initiate in acutely deteriorating
asthma or to treat acute symptoms; use
with additional LABA (do not combine
LABAs because of risk of overdose);
localized infections (Candida albicans
infection of mouth and throat may
occur); immunosuppression (potential
worsening of infections); pneumonia
(increased risk in patients with COPD);
cardiovascular and CNS disorders;
hypercorticism and adrenal suppression;
decreased bone mineral density; growth
effects; glaucoma and cataracts;
metabolic effects (be alert to
eosinophilic conditions, hypokalemia
and hyperglycemia); patients with
convulsive disorders, thyrotoxicosis,
diabetes mellitus and ketoacidosis.
Adverse Drug Reactions:
Common: Dizziness, dysphonia, headache,
nausea, palpitations, throat irritation,
upper respiratory tract infection and
inflammation, tremor, vomiting.
Less Common: Agitation, hyperactivity in
children, hyperglycemia (high-dose),
insomnia, tachycardia.
Rare: Allergic reactions, including urticaria,
angioedema and anaphylaxis;
hypokalemia, lactic acidosis, paradoxical
bronchospasm.
Drug Interactions:
Avoid concomitant use with:
Beta-blockers – these may antagonize the
therapeutic effect of beta2 agonists and
may precipitate asthma and severe
bronchospasm.
Corticosteroids (e.g., hydrocortisone), diuretics
(e.g., furosemide and
hydrochlorothiazide) and theophylline –
serious hypokalemia may occur with
high doses of beta2 agonists; possibly
increased risk of this adverse effect
when given with these drugs.
CYP450 3A4 inhibitors (e.g., ritonavir) – may
cause systemic corticosteroid and
cardiovascular effects (decreased
metabolism).
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, antipsychotics,
calcineurin inhibitors, high-dose thiazide
diuretics and somatropin) – beta2
agonists increase blood glucose
concentration; may increase the risk of
hyperglycemia when given with these
drugs.
Drugs reducing potassium concentration (e.g.,
amphotericin B and diuretics) – beta2
agonists can reduce potassium
concentration, increasing the risk of
hypokalemia; if given with these drugs;
there is enhanced risk of adverse
effects.
Sympathomimetic amines (e.g., ephedrine,
phenylephrine and pseudoephedrine) –
possibly result in excess sympathetic
stimulation and sympathetic adverse
effects (e.g., tremor, tachycardia and
headache).
Administration: Should be administered twice
daily every day by the orally inhaled route
only; after inhalation, the patient should
rinse the mouth with water without
swallowing.
Pregnancy Category: C
ATC Code: R03AK06
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RESPIRATORY SYSTEM
Precautions:
IPRATROPIUM Although side- or adverse effects are less
Rx common at usual therapeutic doses,
their potential occurrence still exists
when given beyond recommended
Inhalation: levels.
MDI: Prostatic hypertrophy; glaucoma (symptoms
20 micrograms/dose x 200 doses (as bromide) may worsen; care needed to protect the
patient's eyes from drug powder or
Resp. Soln. (for nebulization): nebulized drug); myasthenia gravis;
250 micrograms/mL, 2 mL (unit dose) (as medical supervision is necessary for first
bromide) dose of nebulized solution (potential risk
of paradoxical bronchospasm);
A selective, anticholinergic bronchodilator that paradoxical bronchospasm (may occur
is a quaternary ammonium compound with use of inhaled bronchodilating
chemically related to atropine, and agents; this should be distinguished
provides local, site-specific effect rather from inadequate response); elderly (they
than a systemic effect. may find it difficult to use the MDI; a
spacer device may be useful; monitor
Indications: Chronic asthma; chronic urinary function in elderly men with
obstructive pulmonary disease, benign prostatic hypertrophy while on
including chronic bronchitis and this medication).
emphysema. Pregnancy (inhaled ipratropium may be
recommended for use as additional
Contraindications: Known hypersensitivity to therapy for pregnant women with severe
ipratropium or any component of the asthma exacerbations); breastfeeding
formulation, and to atropine or any of its (caution when administering to nursing
derivatives. women).

Dose: Adverse Drug Reactions:

Adjunct in acute bronchospasm, by inhalation Common: Back pain, bronchitis, COPD
of nebulized solution, ADULT, 500 exacerbation, cough, dry mouth,
micrograms repeated as required; CHILD dyspepsia, dyspnea, headache,
6-12 years, 250 micrograms; maximum, influenza-like symptoms, nausea,
1 mg daily; CHILD <up to 6 years, 125- sinusitis, taste disturbance, throat
250 micrograms; maximum, 1 mg daily. irritation, urinary tract infections.
Chronic asthma, chronic obstructive Less Common: Blurred vision, dizziness.
pulmonary disease, by aerosol Rare: Acute closed-angle glaucoma, allergy
inhalation, ADULT, 20-40 micrograms, 3- (urticaria, rash, angioedema,
4 times daily; CHILD 6-12 years, 20-40 anaphylaxis), atrial fibrillation,
micrograms 3 times daily; CHILD <up to constipation, dental caries, dryness of
6 years, 20 micrograms 3 times daily. skin, palpitations, tachycardia, urinary
Chronic obstructive pulmonary disease, by retention.
inhalation of nebulized solution, ADULT,
250-500 micrograms 3-4 times daily. Drug Interactions:
Avoid concomitant use with:
Dose Adjustments: Analgesics (Opioids) – anticholinergics may
Renal and Hepatic Impairment: enhance their adverse effect, specifically
Use drug with caution for mild to moderate the risk of constipation and urinary
impairment; for severe impairment, the retention.
patient should be referred to a specialist. Anticholinergic drugs or other drugs with
anticholinergic effects (see Appendix –

Page | 310
RESPIRATORY SYSTEM
Table A) – these increase ipratropium’s
therapeutic effect and risk of adverse
effects (including central anticholinergic
delirium that is often missed); avoid
these combinations if possible (if
combination is required, monitor the
patient, and reduce dose).
Thiazide diuretics – their serum concentration
may be increased by anticholinergics.
Administration: Dilute solution for nebulization
to 2-3 mL with sodium chloride 0.9%.
Prior to initial use.
NOTE: Do not reduce or stop inhaled
corticosteroids even if the patient feels
better after starting this drug. Do not let
the mist from the nebulizer get into the
eyes (close eyes or wear eye protection).
Pregnancy Category: B
ATC Code: R03BB01
IPRATROPIUM +
Rx SALBUTAMOL
Inhalation:
MDI:
21 micrograms ipratropium (as bromide) +
120 micrograms salbutamol x 200 doses
x 10 mL
Resp. Soln. (for nebulization):
500 micrograms ipratropium (as bromide
anhydrous) + 2.5 mg salbutamol (as base)
x 2.5 mL (unit dose)
A combination of a cholinergic antagonist and
a short-acting, beta2-adrenoceptor
agonist, which is used for the treatment
of chronic obstructive pulmonary
diseases; in which monotherapy is
deemed to be insufficient.
Indications: Treatment of COPD in patients who
are currently on a regular bronchodilator,
who continue to have evidence of
bronchospasm, and require a second
bronchodilator.
Contraindications: Known hypersensitivity to
any of the ingredients; hypersensitivity to
atropine or any of its derivatives;
tachyarrhythmias; and hypertrophic
obstructive cardiomyopathy [See also
under individual monographs].
Dose:
Bronchospasm, by inhalation, ADULT, one
inhalation four times a day, should not
exceed six inhalations in 24 hours.
Treatment of acute attacks, by inhalation using
a suitable nebulizer or an intermittent
positive pressure ventilator, ADULT, 1
unit-dose vial (2 unit-dose vials may be
required for severe cases, which have
not been relieved by 1 unit-dose vial;
patients should consult the physician
immediately); for maintenance
treatment, 1 unit-dose vial for 3-4 times
daily.
NOTE: The unit-dose vial should not be taken
orally or administered parenterally. The
content does not need to be diluted for
nebulization.
Dose Adjustments:
Renal and Hepatic Impairment:
Use drug with caution for mild to moderate
impairment; for severe impairment, the
patient should be referred to a specialist.
Precautions:
Some preparations contain soya lecithin (do
not use in patients allergic to soya
lecithin or related food products, such as
soybean and peanut).
Patients with cardiovascular system disorders
(use with caution due to beta-adrenergic
stimulation); urinary retention (use with
caution in patients with prostatic
hyperplasia or bladder-neck
obstruction); paradoxical bronchospasm
(discontinue immediately and treat with
alternative therapy); ocular effects
(avoid spraying into the eyes; contact a
physician if blurred vision, halos, or
other visual disturbances occur);
carefully monitor patients with narrow-
angle glaucoma; hypersensitivity
reactions (discontinue treatment); in
Page | 311
RESPIRATORY SYSTEM
patients with hyperthyroidism, diabetes
mellitus or convulsive disorders.
Pregnancy (restricted to those patients in
whom the benefits clearly outweigh the
risk; potential beta-agonist interference
with uterine contractility); safety and
efficacy have not been established for
children.
Adverse Drug Reactions:
Common: Back pain, bronchitis, cough,
dryness of mouth, dyspepsia, dyspnea,
headache, influenza-like symptoms,
musculoskeletal pain, myalgia,
nasopharyngitis, nausea, pharyngitis,
sinusitis, taste disturbance, throat
irritation, tremor, upper respiratory
inflammation and infection, urinary tract
infection.
Less Common: Agitation, blurred vision,
diarrhea, dizziness, fatigue, hyperactivity
in children, hyperglycemia (high-dose),
hypertension, insomnia, vomiting.
Rare: Acute closed-angle glaucoma,
arrhythmias, asthenia, atrial fibrillation,
chest discomfort, constipation, dental
caries, dryness of skin, eye pain,
hypersensitivity reactions (including
anaphylaxis, angioedema,
bronchospasm, rash, urticaria and
oropharyngeal edema); hypokalemia,
palpitations, paradoxical bronchospasm,
tachycardia, urinary retention, wheezing.
Drug Interactions:
Monitor closely with:
Corticosteroids (e.g., hydrocortisone), diuretics
(e.g., furosemide and
hydrochlorothiazide) and theophylline –
serious hypokalemia may occur with
high doses of beta2 agonists; possibly
increased risk of this adverse effect
when given with these drugs.
Drugs reducing potassium concentration (e.g.,
amphotericin B and diuretics) – beta2
agonists can reduce potassium
concentration, increasing the risk of
hypokalemia; if given with these drugs,
there is enhanced risk of adverse
effects.
Page | 312
MAO inhibitors and Tricyclic Antidepressants –
these may potentiate effect of
salbutamol on the vascular system.
Avoid concomitant use with:
Anticholinergic drugs or other drugs with
anticholinergic effects (see Appendix –
Table A) – these increase the
combination’s therapeutic effect and
adverse effects (including central
anticholinergic delirium that is often
missed); avoid these combinations if
possible (if the combination is required,
monitor the patient, and reduce their
dose if necessary).
Anticholinesterases (e.g., neostigmine and
pyridostigmine) – combining
anticholinergics with these drugs, which
increase acetylcholine concentration,
will antagonize the anticholinergic effect.
Beta-blockers – these may antagonize the
therapeutic effect of salbutamol in the
combination, and may precipitate
asthma.
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, antipsychotics,
calcineurin inhibitors, high-dose thiazide
diuretics and somatropin) – beta2
agonists increase blood glucose
concentration; may increase the risk of
hyperglycemia when given with these
drugs.
Sympathomimetic amines (e.g., ephedrine,
phenylephrine and pseudoephedrine) –
possibly result in excess sympathetic
stimulation and sympathetic adverse
effects (e.g., tremor, tachycardia, and
headache).
Administration: Metered-dose inhalers require
good hand-breath coordination
(unsuitable for use alone in children <8
years or for people with poor dexterity).
The respiratory solution (for
nebulization) should be administered via
a mouth piece. If this is not available, a
nebulizer mask should be used and it
should fit perfectly; patients who may be
predisposed to glaucoma should be
warned specifically to protect their eyes.
RESPIRATORY SYSTEM
Pregnancy Category: C
ATC Code: R03AL02
MONTELUKAST
Rx
Oral: 4 mg granules (as sodium salt), sachet
4 mg and 5 mg chewable tablet
(as sodium salt)
10 mg tablet (as sodium salt)
A selective, leukotriene-receptor inhibitor,
which antagonizes airway smooth
muscle contraction and inflammation
caused by leukotrienes.
Indications: Prophylaxis and treatment of
asthma (as an adjunctive therapy in
combination with a corticosteroid);
symptomatic relief of seasonal allergic
rhinitis in patients with asthma.
NOTE: There is a place for montelukast in
children aged 2-5 years with intermittent
viral-induced asthma, where
leukotrienes play a minor role.
Contraindication: Known hypersensitivity to
montelukast or any component of the
formulation.
Dose:
Prophylaxis of asthma, by mouth, ADULT and
CHILD >15 years, 10 mg once daily in
the evening; CHILD 6-15 years, 5-mg
chewable tablet once daily in the
evening; CHILD 2-6 years, 4-mg
chewable tablet once daily in the
evening; CHILD 6-23 months, one
packet of 4-mg oral granules.
Seasonal allergic rhinitis, ADULT and CHILD
>15 years, 10 mg/day in the evening.
Dose Adjustments:
Renal and Hepatic Impairment:
Same dosage as in patients with normal
function may be used in patients with
mild to moderate impairment; for severe
impairment, the patient should be
referred to a specialist.
Precautions:
WARNING: Montelukast has no role in the
treatment of status asthmaticus. It
cannot be substituted for inhaled or oral
corticosteroids especially for persistent
asthma. It should not be used as
monotherapy for exercise-induced
bronchospasm.
Eosinophilia and vasculitis; neuropsychiatric
events (behavioral changes) have been
reported in patients using this drug;
phenylketonuria (chewable tablet
contains aspartame); patients are
instructed to have appropriate rescue
treatment available while on
montelukast; when this is being given
with systemic corticosteroids,
appropriate tapering of corticosteroids is
needed under medical supervision;
children (possibly increased risk of
neuropsychiatric adverse effects; limited
data).
Pregnancy (there is limited evidence in the safe
use of montelukast; however, it can be
administered at normal dose in women
who have shown a significant
improvement in asthma, which is not
achievable with other drugs before
becoming pregnant); breastfeeding
(avoid use unless essential).
NOTE: Rarely, the reduction of a systemic
corticosteroid while on another
leukotriene receptor antagonist has
been reported to manifest with
eosinophilia, vasculitic rash, worsening
pulmonary symptoms, cardiac
complications, or neuropathy sometimes
presenting as Churg-Strauss syndrome.
Adverse Drug Reactions:
Common: Abdominal pain and discomfort,
cough, diarrhea, fatigue, fever,
headache, hyperkinesia, otitis media,
pharyngitis, rash, sinusitis, thirst, upper
respiratory infection, weakness.
Less Common: Abnormal dreams, arthralgia,
bruising, dizziness, dry mouth,
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RESPIRATORY SYSTEM
dyspepsia, edema, epistaxis,
hypesthesia, malaise, myalgia,
paresthesia, pruritus, seizures, sleep
disturbances, sleepwalking.
Rare: Allergy, including urticaria, angioedema,
and anaphylaxis; bleeding, Churg-
Strauss syndrome, disorientation,
eosinophilia, erythema multiforme,
erythema nodosum, hallucinations,
hepatic disorders, mood or behavioral
changes, e.g., anxiety, depression and
aggression; neuropsychiatric effects,
e.g., nightmares and hallucinations;
palpitations, suicidal thoughts and
behavior, tremor.
Drug Interactions:
Monitor closely with:
CYP450 enzyme inducers (e.g., phenobarbital
and rifampicin) – these decrease the
AUC of montelukast, possibly reducing
its clinical therapeutic effect.
Administration: Take the drug at only one dose
daily in the evening. Administer the oral
granules (sachet) within 15 minutes
after opening the packet (with or without
mixing with food).
NOTE: Do not use this drug to relieve symptoms
of an asthma attack; use a short-acting
reliever.
Pregnancy Category: B
ATC Code: R03DC03
SALBUTAMOL
Rx
Oral: 2 mg/5 mL syrup, 60 mL (as sulfate)
Inhalation:
Metered Dose Inhaler:
100 micrograms/dose x 200 actuations
(as sulfate)
Page | 314
Breath-Actuated MDI:
100 micrograms/dose x 200 actuations
(as sulfate)
Resp. Soln. (for nebulization):
1 mg/mL, 2.5 mL unit dose (as sulfate)
2 mg/mL, 2.5 mL unit dose (as sulfate)
A short-acting, beta2-adrenergic agonist used
in the treatment, or prevention of
bronchospasm.
Indications: Prophylaxis and treatment of
asthma; bronchospasm in patients with
reversible obstructive airway disease;
prevention of exercise-induced
bronchospasm.
Contraindications: Known hypersensitivity to
salbutamol or any component of the
formulation; severe pre-eclampsia and
eclampsia; intrauterine infection,
intrauterine fetal death; ante-partum
hemorrhage, placenta praevia and cord
compression; threatened miscarriage;
cardiac disease.
Dose:
Chronic asthma, by mouth, ADULT, 2-4 mg 3-4
times daily; in some patients, up to a
maximum of 8 mg 3-4 times daily; CHILD
6-12 years, 2 mg 3-4 times daily; CHILD
2-6 years, 1-2 mg 3-4 times daily; CHILD
<2 years, 100 micrograms/kg 4 times
daily;
Chronic asthma (as an adjunct in stepped
treatment), by aerosol inhalation,
ADULT, 100-200 micrograms (1-2 puffs)
up to 3-4 times daily; CHILD, 100
micrograms (1 puff) 3-4 times daily,
increased to 200 micrograms (2 puffs)
3-4 times daily if necessary.
Prophylaxis of exercise-induced
bronchospasm, by aerosol inhalation,
ADULT, 200 micrograms (2 puffs);
CHILD, 100 micrograms (1 puff)
increased to 200 micrograms (2 puffs) if
required.
Relief of acute bronchospasm, by aerosol
inhalation, ADULT, 100-200 micrograms
RESPIRATORY SYSTEM
(1-2 puffs); CHILD, 100 micrograms (1
puff) increased to 200 micrograms (2
puffs) if necessary.
Severe acute asthma, chronic bronchospasm
(unresponsive to conventional
treatment), by inhalation of nebulized
solution, ADULT and CHILD >18 months,
2.5 mg repeated up to 4 times daily; may
be increased to 5 mg if necessary
(consider medical assessment since
alternative therapy may be indicated);
CHILD <18 months, clinical efficacy
uncertain (transient hypoxemia may
occur – consider oxygen
supplementation).
Dose Adjustments:
Elderly:
Start with a lower dose than the usual adult
dosage; gradually increase if needed.
Renal and Hepatic Impairment:
Use with caution for high-dose treatments.
Precautions:
WARNING: Excessive use and reliance on
Beta2-agonists for the treatment of
asthma without an anti-inflammatory
agent have been associated with an
increased incidence of sudden deaths.
Beta2-agonists inhalation can
occasionally cause paradoxical
bronchospasm and hypoxemia.
Paradoxical bronchospasm may occur (should
be treated immediately with alternative
therapy); hyperthyroidism; myocardial
insufficiency, arrhythmias, susceptibility
to QT-interval prolongation, hypertension
(risk of cardiovascular adverse effects);
diabetes mellitus, especially IV
administration (ketoacidosis reported;
monitor blood glucose); discontinue
treatment if the patient develops signs of
pulmonary edema.
Pregnancy (high doses should be given
through inhalation only – parenteral use
can affect the myometrium and may
cause cardiac problems); breastfeeding
(monitor infant; safe in usual dosage).
Adverse Drug Reactions:
Common: Cough, headache, musculoskeletal
pain, palpitations, throat irritation,
tremor, upper respiratory inflammation,
viral respiratory infections.
Less Common: Agitation, hyperactivity in
children, hyperglycemia (high-dose),
insomnia, tachycardia.
Rare: Allergic reactions, hypokalemia, lactic
acidosis, paradoxical bronchospasm.
Drug Interactions:
Monitor closely with:
Digoxin – possibly reduced plasma digoxin
concentration.
Methyldopa – acute hypotension reported with
salbutamol infusion.
Avoid concomitant use with:
Beta-blockers – these may antagonize the
therapeutic effect of beta2 agonists and
may precipitate asthma.
Corticosteroids, theophylline and diuretics –
serious hypokalemia may occur with
high doses of beta2 agonists; possibly
increased risk of this adverse effect
when given with these drugs.
Drugs increasing blood glucose concentration
(e.g., glucocorticoids, antipsychotics,
calcineurin inhibitors, high-dose thiazide
diuretics and somatropin) – beta2
agonists increase blood glucose
concentration; may increase risk of
hyperglycemia when given with these
drugs.
Drugs reducing potassium concentration (e.g.,
amphotericin B, and diuretics) – beta2
agonists can reduce potassium
concentration, increasing the risk of
hypokalemia; if given with these drugs,
there is enhanced risk of adverse
effects.
Sympathomimetic amines (e.g., ephedrine,
phenylephrine and pseudoephedrine) –
possibly result in excess sympathetic
stimulation and sympathetic adverse
effects (e.g., tremor, tachycardia and
headache).
Administration: Tablet should be taken on an
empty stomach. Take 1 hour before, or 2
hours after, meals. Multidose solution
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RESPIRATORY SYSTEM
for nebulization may need dilution with
0.9% sodium chloride to obtain final
volume for the nebulizer.
Pregnancy Category: C
ATC Code: R03AC02
COUGH AND COLD
BUTAMIRATE
Rx
Oral: 50 mg MR tablet (as citrate)
7.5 mg/5 mL syrup, 120 mL
(as citrate)
A centrally-acting antitussive, which is neither
chemically nor pharmacologically related
to the opioids, and is intended as a
cough suppressant.
Indications: Chronic, non-productive, irritative
cough; symptomatic treatment of cough
of various origins.
Contraindications: Known hypersensitivity to
butamirate or any component of the
formulation; diabetes mellitus.
Dose:
Cough, by mouth, ADULT and CHILD >12 years
old, 10-20 mg every 4 hours or 30 mg
every 6-8 hours; INFANT and CHILD 6-12
years old, 1 mg/kg/day divided every 6-
8 hours;
Alternatively, ADULT, 1 tablet 2-3 times
daily; ADULT and CHILD >9 years old, 1-
2 tablespoon 3 times a day; CHILD 1-9
years, 1-2 teaspoon syrup 2-3 times
daily.
Dose Adjustment:
Renal Impairment:
Eliminated renally; use with caution.
Precautions:
Page | 316
Use in the first trimester of pregnancy is not
recommended (during the rest of
pregnancy, use it only if drug therapy is
essential); effects on the ability to drive,
or operate machinery (butamirate may
cause somnolence; caution while driving
or performing other tasks which require
alertness).
Adverse Drug Reactions:
Rare: Diarrhea, dizziness, GI discomfort,
nausea, skin rash, somnolence,
urticaria.
Drug Interactions:
Avoid concomitant use with:
Expectorants – may lead to the stagnation of
the mucus in the respiratory tract,
increasing the risk of bronchospasm and
airways infection.
Penicillins, phenobarbital, salicylates and
tetracyclines – butamirate has been
reported to be incompatible with these
drugs.
Administration: May be taken with or without
food.
Pregnancy Category: C
ATC Code: R05DB13
ANTIHISTAMINES
CETIRIZINE
Rx
Oral: 10 mg tablet (as dihydrochloride)
10 mg/mL drops, 10 mL
(as dihydrochloride)
1 mg/mL solution, 30 mL and 60 mL
(as dihydrochloride)
5 mg/5 mL syrup, 30 mL
(as dihydrochloride)
A piperazine-derived, long-acting, second-
generation H1 receptor antagonist,
which is often better tolerated than
RESPIRATORY SYSTEM
sedating antihistamines due to less
sedating and less anticholinergic effects.
Indications: Perennial and seasonal allergic
rhinitis, and other allergic symptoms
such as hay fever, conjunctivitis, and
chronic idiopathic urticaria.
Contraindications: Known hypersensitivity
reactions to cetirizine, levocetirizine or
hydroxyzine (cetirizine is hydroxyzine’s
active metabolite) or any component of
the formulation; severe renal
impairment.
Dose:
Symptomatic relief of allergy, by mouth, ADULT,
10 mg once daily or 5 mg twice daily
(may be increased as necessary to the
maximum recommended daily dose of
20 mg); CHILD >6 years, 10 mg/day or
5 mg twice daily; CHILD 2-6 years, 5 mg
once daily or 2.5 mg twice daily; CHILD
1-2 years, oral drops, 0.25 mg/kg twice
daily.
Dose Adjustments:
Elderly ≥77 years of age:
Use lower dose (5 mg/day).
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose
reduction is warranted (5 mg/day);
Contraindicated for severe renal impairment.
Precautions:
WARNING: May cause CNS depression which
may impair physical or mental abilities;
patients should be cautioned about
performing tasks that require mental
alertness, such as operating machinery
or driving.
CNS stimulation may occur with
antihistamines, especially in children
(caution is advised in patients suffering
from epilepsy); children and the elderly
(risk of sedation and anticholinergic
effects are increased).
Renal impairment; hepatic impairment; excess
alcohol intake, and use of other sedative
drugs should be avoided.
Not recommended for children <12 months, or
for breastfeeding mothers (cetirizine is
excreted into breast milk).
Adverse Drug Reactions:
Common: Dizziness, drowsiness, dryness of
mouth, fatigue, headache, insomnia,
malaise, nausea, pharyngitis,
somnolence.
Less Common: Abdominal pain, anorexia,
arthralgia, chest pain, diarrhea,
dyspepsia, dyspnea, elevated liver
enzymes, epistaxis, fever, flushing,
increased appetite, myalgia,
tachycardia, thirst, vomiting, weight gain.
Rare: Dystonias, hemolytic anemia, hepatitis,
hypersensitivity, including anaphylaxis
and bronchospasm; hypotension, rash,
thrombocytopenia.
Drug Interactions:
Monitor closely with:
Acetylcholinesterase Inhibitors (central) –
these may diminish the therapeutic
effect of cetirizine.
Analgesics (opioids) – their adverse effects
may be enhanced by cetirizine,
specifically constipation and urinary
retention.
Anticholinergics (e.g., ipratropium, tiotropium)
– their anticholinergic effect may be
enhanced by cetirizine.
CNS Depressants (e.g., alcohol, sedatives) –
these may potentiate the sedative effect
of cetirizine; cetirizine may also enhance
the adverse effect of other CNS
depressants.
Warfarin – risk of increased INR and epistaxis.
Avoid concomitant use with:
Doxylamine- combination increases risk for
CNS depression and psychomotor
retardation.
Administration: It may be administered with or
without food.
Pregnancy Category: B
ATC Code: R06AE07
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RESPIRATORY SYSTEM
DIPHENHYDRAMINE
Rx
Oral: 25 mg and 50 mg capsule (as
hydrochloride)
12.5 mg/5 mL syrup (as hydrochloride),
30 and 60 mL
Inj.: 50 mg/mL, 1 mL ampul (IM, IV) (as HCl)
A monoethanolamine-derived, first-generation
H1 receptor antagonist that exhibits
antimuscarinic and pronounced
sedative property, with low incidence of
GI side effects.
Indications: Relief of allergic symptoms caused
by histamine release, including rhinitis,
cough, conjunctivitis and allergic
dermatoses; moderate to severe
angioedema and anaphylaxis (adjunct to
epinephrine).
Contraindications: Known hypersensitivity to
diphenhydramine or any component of
the formulation; acute asthma;
neonates or premature infants
(increased susceptibility to
antimuscarinic effects); breastfeeding;
use of the parenteral form as a local
anesthetic.
Dose:
Allergic reactions, by mouth, ADULT, 25-50 mg
every 6-8 hours; CHILD >12 years, 25-
50 mg every 4-6 hours (maximum, 300
mg daily); CHILD 6 to <12 years, 12.5-
25 mg every 4-6 hours (maximum, 150
mg daily); CHILD 2 to <6 years, 6.25 mg
every 4-6 hours (maximum, 37.5 mg
daily).
Allergic reactions, by IM or IV injection, ADULT,
10-50 mg/dose, single doses up to 100
mg may be used if needed (not to exceed
400 mg/day); CHILD, 5 mg/kg/ day or
150 mg/m2/day in divided doses every
6-8 hours (not to exceed 300 mg/day).
Dose Adjustments:
Advanced age:
If used, consider lower doses.
Renal Impairment:
Page | 318
Same dosage as in patients with normal renal
function may be used in patients with
mild-to-moderate renal impairment.
Hepatic Impairment:
Same dosage as in patients with normal
hepatic function may be used in patients
with mild-to-moderate hepatic
impairment; for severe impairment, the
patient should be referred to a specialist
(due to increased risk for coma).
Elderly:
For emergency allergic reactions only; use only
smallest effective dose, 25 mg oral or IV
every 8-12 hours (advanced age
associated with reduced clearance of
drug).
Precautions:
WARNING: May cause sedation; serious
adverse drug interactions are quite
common, potentially fatal in some;
antihistamines can cause
hypersensitivity reactions themselves.
CNS depression (caution in performing tasks
requiring mental alertness); prostatic
hypertrophy, urinary retention,
susceptibility to angle-closure glaucoma,
and pyloroduodenal obstruction;
advanced age (associated with reduced
drug clearance, and increased risk of
confusion, dryness of mouth,
constipation or other anticholinergic
effects, and toxicity); asthma; thyroid
dysfunction; cardiovascular disease;
pediatrics (may cause excitation; more
susceptible to side-effects); epilepsy.
Latter part of third trimester pregnancy (may
cause irritability, paradoxical excitability,
and tremor in neonates).
Adverse Drug Reactions:
Common: Anxiety, blurred vision, constipation,
cough, diarrhea, dizziness, dryness of
mouth, nose and throat, epigastric
discomfort, euphoria, incoordination,
insomnia, nausea, nervousness,
psychomotor impairment, sedation,
RESPIRATORY SYSTEM
sleepiness, thickening of bronchial Contraindications: Known hypersensitivity to
secretions, tinnitus, tremor, vomiting. loratadine or any component of the
Less Common: Hallucinations, headache, formulation; children <2 years of age;
hypotension, palpitations, psychosis, pregnancy; breastfeeding.
restlessness, urinary retention, vertigo.
Rare: Agranulocytosis, arrhythmias, blood Dose:
dyscrasias, convulsions, EPS, hemolytic Chronic idiopathic urticaria and seasonal
anemia, hepatitis, hypersensitivity allergic rhinitis, by mouth, ADULT, 10 mg
reactions, leukopenia, liver disorders, once daily (not to exceed 10 mg per day);
excitation, hallucination, seizures, CHILD >30 kg or >6 years, 10 mg once
paralysis. daily; CHILD <30 kg or 2-5 years, 5 mg
once daily
Drug Interactions: NOTE: Safety and efficacy is not established for
Monitor closely with: allergic rhinitis in CHILD <2 years, and
Beta blockers (e.g., labetalol, metoprolol, for urticaria in CHILD <6 years.
propranolol) – their plasma
concentration and cardiovascular Dose Adjustments:
effects are increased by Renal and Hepatic Impairment:
diphenhydramine. For mild-to-moderate impairment, the dose
CNS depressants (e.g., alcohol, anxiolytic frequency is reduced to alternate days;
sedatives, barbiturates, hypnotics, for severe impairment, the patient
neuroleptics, opioid analgesics) – these should be referred to a specialist.
may potentiate the sedative effect of
diphenhydramine. Precautions:
Renal or hepatic impairment; the elderly
Administration: May be taken with or without (loratadine may be inappropriate in
food. certain comorbidities, such as dementia
and delirium; increased risk of sedation
Pregnancy Category: B and anticholinergic effects);
breastfeeding; prostatic hypertrophy,
ATC Code: R06AA02 urinary retention, susceptibility to angle-
closure glaucoma and pyloroduodenal
obstruction; and epilepsy.

LORATIDINE Adverse Drug Reactions:

Rx
Oral: 10 mg film-coated tablet
5 mg/5 mL syrup, 30 mL
A piperidine-derived, non-sedating, second-
generation H1 receptor antagonist,
which is extensively converted into a
metabolite having a longer half-life.
Indications: Relief of nasal and non-nasal
symptoms of seasonal allergic rhinitis;
hay fever; chronic idiopathic urticaria,
and other allergic dermatological
disorder.
Common: Abdominal pain, blurred vision,
conjunctivitis, drowsiness, dryness of
mouth, dysphonia, earache, epistaxis,
fatigue, GI disturbances, headache,
hyperkinesia, impaired concentration,
influenza-type symptoms, laryngitis,
malaise, nausea, nervousness,
psychomotor impairment, somnolence,
stomatitis, upper respiratory tract
infection, urinary retention, viral
infection, wheezing.
Less Common: Elevated liver enzymes,
increased appetite, insomnia, weight
gain.
Rare: Abnormal hepatic function, agitation,
alopecia, amnesia, angle-closure
glaucoma, blood disorders, bronchitis,

Page | 319
RESPIRATORY SYSTEM
chest pain, confusion, convulsions,
depression, dermatitis, dizziness,
erythema multiforme, EPS, hemoptysis,
hepatic necrosis, hepatitis, hypotension,
hypersensitivity reactions, including
anaphylaxis; hypertension, impotence,
palpitation, peripheral edema, purpura,
seizures, sleep disturbance,
supraventricular tachyarrhythmias,
syncope, tachycardia,
thrombocytopenia, urticaria, vertigo.
Drug Interactions:
NOTE: Sedative interactions apply to a lesser
extent to the non-sedating
antihistamines. Interactions do not
generally apply to antihistamines used
for topical action, as well as inhalation.
Monitor closely with:
Alcohol – its CNS depressant effect may be
enhanced by loratadine.
Analgesics (opioids) – their adverse effects
may be enhanced by loratadine,
specifically constipation and urinary
retention.
Azithromycin- loratadine increases level or
effect of this drug.
CYP3A4 inhibitors (see Appendix) – these may
significantly increase the plasma
concentration of loratadine, thereby
increasing the risk of adverse effects.
Estradiol and estrogens conjugated synthetic-
loratadine increases the level or effect of
these drugs.
SSRIs – their adverse effects may be enhanced
by loratadine, specifically the risk of
psychomotor impairment.
Administration: May be taken with or without
food.
Pregnancy Category: B
ATC Code: R06AX13
Page | 320
HYDROCORTISONE
Rx
Oral: 5 mg and 20 mg tablet
Inj.: 100 mg and 250 mg (as sodium
succinate), vial (IV) 50 mg/mL (as
sodium succinate), 2 mL vial (IM, IV) 125
mg/mL powder (as sodium succinate), 2
mL vial (IV)
A glucocorticoid used for replacement therapy
in adrenal insufficiency, management of
autoimmune and inflammatory
conditions, and as emergency
management of anaphylaxis and severe
systemic allergies.
Indications: Management of autoimmune or
inflammatory conditions; endocrinal
disorders; management of all conditions
requiring corticosteroids; replacement
therapy in cases of adrenocortical
insufficiency (usually in combination
with a more potent mineral corticoid);
hypersensitivity reactions, such as
anaphylactic shock and angioedema;
bilateral adrenalectomy
Dose:
Anti-inflammatory, by IV or IM injection, ADULT,
100 to 500 mg 3 or 4 times daily; CHILD,
2–4 mg/kg every 6 hours for 24 hours,
reduce over subsequent 24 hours or
change to oral prednisone by mouth,
ADULT, 20–240 mg once daily.
Initial control of autoimmune disease, by IV
injection, ADULT, 100–500 mg 3 or 4
times daily according to severity of
condition.
Status asthmaticus, by IV injection, ADULT and
CHILD, 1–2 mg/kg per dose every 6
hours for 24 hours, then maintenance of
0.5–1 mg/kg every 6 hours. Physiologic
replacement, by mouth, CHILD, 0.4–0.8
mg/m2 daily divided in 2–3 divided
doses
Dose Adjustments:
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose
reduction is warranted.
RESPIRATORY SYSTEM
For severe impairment, refer patient to a Avoid concomitant use with medicines that:
specialist. Drugs that decrease bioavailability of
Hydrocortisone: Antacids [separate
Adverse Drug Reactions: doses by at least 2 hours]
Common: Acne, adrenal suppression, Drugs that increase risk of adverse or toxic
amenorrhea, bruising, delayed wound effects of Hydrocortisone:
healing, dyslipidemia, dyspepsia, Nondepolarizing Neuromuscular-
edema, fat redistribution, fractures, Blocking Agents, (increased muscle
growth retardation, hirsutism, weakness, possibly progressing to
hyperglycemia, hypertension, polyneuropathies and myopathies),
hypokalemia, increased appetite, Pimecrolimus, Tacrolimus (Topical)
increased susceptibility to infection, Diuretics e.g., Furosemide,
masking of signs of infection, muscle Hydrochlorothiazide (hypokalemia),
weakness and wasting, myopathy, Drugs controlling Blood Glucose
osteoporosis, psychiatric effects, skin Concentration (may increase blood
atrophy, sodium and water retention, glucose concentration; may alter control
weight gain of diabetes), Vaccines (Live) – Adverse or
Less Common: Glaucoma, ocular toxic effects are increased by
hypertension, osteonecrosis (femoral hydrocortisone.
and humeral heads) Amlodipine, Antihypertensives (e.g., Enalapril,
Rare: Anaphylactoid reaction, Isosorbide Dinitrate, Methyldopa),
chorioretinopathy (central), euphoria, Diuretics (e.g., Furosemide,
hypersensitivity reactions, hypomania, Hydrochlorothiazide (antagonizes
peptic ulceration, tendon rupture hypotensive effect), BCG (Intravesical) –
therapeutic effects are reduced by
Drug Interactions: hydrocortisone.
Monitor closely with medicines that: Hyaluronidase, Vaccines (Inactivated
Warfarin – hydrocortisone enhances [complete all age appropriate
anticoagulant effect vaccinations at least 2 weeks prior to
Salicylates– with increased risk for GI starting Dexamethasone; if vaccinated
ulceration and bleeding during Dexamethasone therapy,
Acetylcholinesterase Inhibitors (increased revaccinate at least 3 months after
muscular weakness), Amphotericin B, discontinuation]), Vaccines (Live) –
Thiazide Diuretics, Loop Diuretics therapeutic effects may be reduced by
(hypokalemic effect), Androgens (fluid hydrocortisone.
retaining effect), COX-2 Inhibitors e.g.
Celecoxib, NSAID (Non-selective), Administration: Give directly or dilute in normal
Quinolone Antibiotics (tendonitis; tendon saline or D5W. Administer within 24
rupture) – adverse or toxic effects may be hours after diluting
increased by hydrocortisone
Drugs that reduce absorption of Pregnancy Category: C; D in the 1st trimester
Hydrocortisone:
Bile Acid Sequestrants Reduces ATC Code: H02AB09
therapeutic effect of the following drugs:
Antidiabetic Agents, Calcitriol, Urea Cycle
Disorder Agents (increases protein
catabolism and plasma ammonia
concentrations, increasing doses of Urea
Cycle Disorder Agents needed to maintain
concentrations in target range)

Page | 321
RESPIRATORY SYSTEM
LAGUNDI [Vitex negundo L.
Rx (Fam. Verbenaceae)
Oral: 300 mg and 600 mg tablet
300 mg/5 mL syrup, 60 mL and 120 mL
A natural, medicinal preparation from the
leaves of Vitex negundo Linn. (Fam.
Verbenaceae), which is used for the
relief of cough.
NOTE: See supplement on Guide to the Use of
the Common Philippine Medicinal
Plants.
Indications: For the relief of mild to moderate
cough due to common colds and flu.
Contraindications: Patients with severe allergy
to Vitex negundo or any of its
components
Dose: to 1 tsp of 300mg/5 mL syrup 3 times
per day. Cough, by mouth, ADULT, as
600 mg tablet, 1 tablet 3–4 times daily;
as 300 mg/5 mL syrup, 2 tsp 3-4 times
per day; CHILD 7–12 years, 1 tablet 3–4
times daily; as 300 mg/5 mL syrup, 10
mL (2 tsp) 3–4 times daily,; CHILD, 15
mg/kg per dose (0.25 mL/kg per dose
for 300 mg/5 mL) administered 3 times
daily; CHILD >40 kg body weight, 2 tsp 3
Page | 322
times per day of 300 mg/5 mL; CHILD 6–
12 years (20–40 kg), 1½ to 2 tsp of 300
mg/5 mL 3 times per day; CHILD 4–6
years (15.5–20 kg), 1 tsp of 300 mg/5
mL 3 times daily; CHILD 2–4 years (10–
15.5 kg), ½
Dose Adjustments: All clinical trials were
performed in patients with normal renal
and liver function tests; no reports of
adverse events in patients with renal
and liver dysfunction.
Precautions:
Patients with known allergy to lagundi plants.
Adverse Drug Reactions:
Mild adverse effects have been observed, such
as itchiness, nausea, vomiting and
diarrhea.
Drug Interactions: Possible interaction with
ibuprofen, potentiates anti-inflammatory
activity
Administration: For syrup preparation, shake
well before use. May be taken with or
without food.
Pregnancy Category: In vitro and animal
studies have shown Lagundi to be non-
mutagenic and non clastogenic.
SENSORY ORGANS
SENSORY ORGANS
OPHTHALMIC ANTIBACTERIAL
PREPARATIONS
ERYTHROMYCIN
Rx
Eye Ointment: 0.5%, 3.5 g tube
A macrolide antibiotic used for superficial
ocular infections caused by susceptible
organisms, and is highly recommended
for the prevention of ophthalmia
neonatorum.
Indication: Treatment of superficial ocular
infections involving the conjunctiva or
cornea caused by organisms susceptible
to erythromycin.
Contraindications: Known hypersensitivity to
erythromycin, or any component of the
formulation; minor ocular irritation;
prophylaxis of ophthalmia neonatorum
from both N. gonorrhoeae and C.
trachomatis.
Dose:
Conjunctivitis, ADULT, apply ½ inch (1.25 cm)
on the eyes every 3-4 hours, 2-6 times a
day depending on the severity of the
infection.
Prophylaxis of ophthalmia neonatorum, apply
1 cm ribbon of 0.5% ointment into each
lower conjunctival sac immediately after
birth, then gently massage the closed
eyelids to spread the ointment.
NOTE: Prophylaxis should not be delayed by
more than 1 hour after delivery since
delayed application may reduce efficacy.
Ideally, a new tube or a single-use
container of ointment should be used for
each neonate.
Dose Adjustment: No information found.
Precautions:
Pregnancy and breastfeeding; this may result
in overgrowth of non-susceptible
organisms, including fungi; for
ophthalmic use only.
Adverse Drug Reactions:
Common: Minor ocular reactions, redness.
Rare: Hypersensitivity reactions.
Drug Interactions: No information found.
Administration: The ointment should be
applied directly to the infected eye
through the pocket made by the lower lid
and the eye. It is advisable to apply the
ointment at night.
NOTE: Avoid contaminating the applicator tip
with the material from the eyes, fingers
or other sources.
Pregnancy Category: B
TOBRAMYCIN
Rx
Eye Drops Solution: 0.3%, 5 mL bottle
Eye Ointment: 0.3%, 3.5 g tube
An aminoglycoside used for ocular infections,
such as conjunctivitis, caused by gram-
negative organisms, including P.
aeruginosa and S. aureus.
Indication: Treatment of superficial infections
of the eye which are caused by
susceptible organisms.
Contraindication: Known hypersensitivity to
tobramycin, and other ocular
aminoglycosides, or any component of
the formulation.
Dose: Mild to moderate ocular infections,
ointment: apply ½ inch (1.25 cm) 2-3 times a
day; solution: instill 1 drop every 2-4 hours for
2 days; then if there is improvement, 1 drop 4
times daily for 5 days.
Page | 323
SENSORY ORGANS
Severe ocular infections (including
Pseudomonas aeruginosa), ointment:
apply ½" (1.25 cm) every 3-4 hours;
solution: instill 1 drop every 30-60
minutes; then reduce to less frequent
intervals.
Dose Adjustment: No information found.
Precautions:
Hypersensitivity reactions; contact-lens
wearers; superinfections.
NOTE: The ophthalmic solution is not for
injection, and should not be injected
subconjunctivally or directly into the
anterior chamber of the eye.
Adverse Drug Reactions:
Common: Eye pain, ocular hyperemia.
Less Common: Conjunctivitis, eye pruritus,
eyelid edema, headache, increased
lacrimation, ocular discomfort,
superficial punctuate keratitis.
Rare: Delayed corneal epithelial wound
healing, hypersensitivity reactions,
retinal toxicity.
Drug Interactions: Drug interactions are far
less likely to occur since systemic
absorption through topical
administration is usually very low.
Administration: Place a small amount of
ointment into the pocket made by the
lower lid and the eye. A ½-inch strip of
ointment is usually enough, unless
otherwise directed. It is advisable to
apply the ointment at night and the
drops during daytime.
NOTE:
• In case of concomitant therapy with
other topical ophthalmic medicinal
products, an interval of 10 minutes
should be allowed between successive
applications.
• If necessary, drops should precede
ointments because the ointments
effectively impede the absorption of the
drops.
Pregnancy Category: B
Page | 324
TOBRAMYCIN +
Rx DEXAMETHASONE
Ophth.:0.3% tobramycin + 0.1%
dexamethasone eye drops
suspension, 5 mL bottle
0.3% tobramycin + 0.1%
dexamethasone eye ointment, 3.5 g
tube
A sterile topical anti-inflammatory
(dexamethasone) and anti-infective
(tobramycin) product indicated for
ophthalmic use.
Indication: Steroid-responsive ocular
inflammation with suspected or
confirmed bacterial infection
Contraindications: Viral infections of cornea
and conjunctiva (e.g., epithelial herpes
simplex keratitis, vaccinia, varicella);
mycobacterial or fungal infection of the
eye; uncomplicated removal of a foreign
body.
Dose:
Ocular inflammation with suspected or
confirmed bacterial infection, into the
eye, ADULT, as eye drops suspension,
instill 1–2 drops into the conjunctival
sac(s) every 4–6 hours, may be
increased to every 2 hours during the
initial 24–hour to 48–hour period,
decrease frequency gradually as
improvement seen; as eye ointment,
apply about ½ inch of ointment into the
conjunctival sac(s) up to 3–4 times daily.
Precautions:
Glaucoma (e.g., optic nerve damage);
Cataracts (e.g., posterior subcapsular
cataract formation with prolonged use);
Sensitivity; Secondary infection;
Children; Pregnancy; Lactation.
Adverse Drug Reactions:
Common: Hypersensitivity reactions, lid itching
and swelling, conjunctival erythema.
Less Common: Increased intraocular pressure,
SENSORY ORGANS
glaucoma, optic nerve damage, posterior
subcapsular cataract formation, delayed
wound healing, secondary infections
(prolonged use).
Administration: For external use only. NOT for
injection.
Do NOT prescribe more than 20 mL or 8
g, initially. Do NOT refill prescription
without further evaluation.
See individual monographs for Tobramycin and
Dexamethasone for other information.
daily for 7 days or as directed by the
physician.
Precautions:
Hypersensitivity; Superinfection; Pregnancy
and lactation (use with caution; safety
has not been established in this
population).
Adverse Drug Reactions:
Less Common: Hypesthesia, paresthesia,
pruritus, rash, urticaria.
Rare: Ear discomfort, hearing disorders, ear
pain.

Pregnancy Category: C Drug Interactions:

Monitor closely with:
Reduces therapeutic effect of Clotrimazole:
Polyene Antibiotics e.g., Nystatin
ANTIBACTERIAL OTIC
PREPARATIONS Administration: Prior to first administration,
remove the closure and put the dropper
assembly in place on the bottle. Avoid
contaminating the dropper with material
CLOTRIMAZOLE from the ear, fingers or other sources.
Rx Warm to room temperature prior to
administration.
Otic: 1% otic solution Lie down with the affected ear upward.
Instill the medication. Remain in this
A broad-spectrum imidazole that acts against position for at least 30 seconds to
fungi (both dermatophytes and yeasts) facilitate penetration of the drops into
and gram-positive cocci (Staphylococcus the external ear canal. Repeat, if
and Streptococcus spp.). necessary, for the opposite ear.
Indication: Treatment of acute bacterial otitis Discard unused portion after treatment
externa caused by organisms is completed.
susceptible to the action of ciprofloxacin,
such as Pseudomonas aeruginosa, Pregnancy Category: C
Staphylococcus aureus, and
Enterobacteriaceae.

NOTE: NOT indicated for the treatment of otitis NEOMYCIN + POLYMYXIN

media Rx B + FLUOCINOLONE
Contraindications:
Known or suspected perforated tympanic Ear drop solution: 3.5mg Neomycin (as sulfate)
membrane. + 10,000 units polymyxin B (as sulfate)
+ 0.025% fluocinolone acetonide /mL, 5
Dose: mL bottle
Otitis externa, into the ear, CHILD ≥2 years, A combination of a corticosteroid and anti-
instill 3 drops into the affected ear twice infectives (aminoglycoside and basic
peptides) used in treating ear diseases.
Page | 325
SENSORY ORGANS
Indications: Otitis externa, with or without
associated otitis media; adjunct therapy
to acute or chronic dermatoses of the
external ear chronic suppurative otitis
media; draining mastoidectomy cavities;
otorrhea from ventilation tubes.
Contraindications: Known hypersensitivity to
neomycin, polymyxin B, or any
component of the formulation; patients
with primary infection of the skin caused
by bacteria, fungi, acne rosacea, perioral
dermatitis; patients with herpes simplex,
vaccinia and varicella; patients with
untreated fungal or viral infections; and
pregnancy (first trimester).
Dose:
Ear infections, instill 3-4 drops 2-4 times daily.
NOTE: Limit treatment to 5-7 days; refer to ENT
specialist if discharge continues.
Precautions:
Patients with perforated eardrum or long-
standing chronic otitis media;
pregnancy; prolonged use.
Adverse Drug Reactions:
Common: Allergic dermatitis.
Less Common: Acneiform eruptions, burning,
decreased hearing, dryness, ear pain,
folliculitis, fungal overgrowth inside ear
canal, hypertrichosis, hypopigmentation,
irritation, itching, miliaria, perioral
dermatitis, secondary infections,
tinnitus.
Rare: Inner ear damage.
Drug Interactions: No information found.
Administration: The ears should be clean and
dry, and the patient should lie with the
affected ear uppermost.
Method of drug application depends on degree
of swelling in ear canal:
• For minimal swelling, instill drops
directly into the ear canal then remain in
position for a few minutes.
• For swelling that narrows the ear canal,
saturate a sponge wick or ribbon gauze
Page | 326
with drops and insert into the ear canal;
review daily until swelling settles.
When using drops, warm container in cup of
warm water if necessary to reduce
viscosity. Gentle massage or pressure on
the tragus (cartilage flap over the
opening of the ear canal) may aid
penetration of the drops.
Pregnancy Category: C
OFLOXACIN
Rx
Otic: 0.3% ear drops solution, 5 mL bottle
A DNA gyrase inhibitor that interferes with
replication, transcription, repair,
recombination, and transposition of
bacterial DNA.
Indications: Otitis externa; chronic suppurative
otitis media; acute otitis media.
Contraindications: Hypersensitivity to ofloxacin
or other members of the quinolone group,
such as oxolinic acid, cinoxacin, norfloxacin,
and ciprofloxacin.
Dose:
Otitis media or chronic suppurative with
perforated tympanic membranes, into the
ear, ADULT and CHILD, instill 10 drops into
affected ear twice daily for 14 days.
Otitis externa, into the ear, ADULT, instill 10
drops into affected ear(s) once daily for 7
days; CHILD 6 months – 13 years, instill 5
drops into affected ear(s) once daily for 7
days.
Acute otitis media with tympanotomy tubes,
into the ear, CHILD 1–12 years, instill 5
drops into affected ear twice daily for 10
days.
Dose Adjustment: Dose adjustment unlikely
due to low systemic absorption.
SENSORY ORGANS
Precautions: ANESTHETICS
Hypersensitivity reactions (e.g., severe
hypersensitivity reactions, including
anaphylaxis, have occurred; itching, LIDOCAINE
urticaria, rash, or edema may occur after a Rx
single dose; Stevens-Johnson, toxic
epidermal necrolysis, vasculitis,
pneumonitis, nephritis, hepatic failure or Topical: 10% spray (as hydrochloride), 50
necrosis, anemia, or cytopenias may occur mL
after multiple doses);
Superinfection; Tendon inflammation or A local anesthetic, which blocks initiation and
rupture; transmission of nerve impulses at the site
Elderly (evaluate the patient's or caregiver's of application by stabilizing neuronal
ability to safely and correctly administer the membrane.
medication);
Pregnancy and lactation (use with caution; Indications: Short duration local surface
safety has not been established). anesthesia (10 to 15 minutes) of the oral
mucous membrane (prior to injection for
Adverse Drug Reactions: oral and dental procedures).
Common: Application site reaction, dizziness,
vertigo, pruritus, taste perversion, Contraindications: Seizures; liver disease;
paresthesia. pregnancy; lactation.
Less Common: Diarrhea, fever, headache,
hearing loss (transient), hypertension, Dose:
nausea, otorrhagia, tinnitus, tremor, Procedure-specific dose recommendations for
vomiting, xerostomia. adults using lidocaine spray:

Maximum Dosage

Maximum Dosage
for
(mg) for Short
Drug Interactions: No known significant
interactions
Dosage (mg)
Recommended

Procedures

Procedures
Prolonged
Administration: NOT for injection or for

(mg)
ophthalmic use.
Area

Prior to use, warm solution by holding

Oral and
container in hands for 1–2 minutes.
dental
Lie down with the affected ear upward. Instill
procedur
the medication. Pump the tragus (cartilage
es 20–
flap over the opening of the ear canal) 4 500 600
(e.g., 200
times to ensure penetration of medication.
prior to
Remain in this position for 5 minutes.
injecti
on)
Pregnancy Category: C
NOTE: For short procedures, give drug for less
than 1 minute. For prolonged procedures,
the duration of application is>5 minutes.
* Reduce dose during controlled ventilation.

Page | 327
SENSORY ORGANS
Local anesthetic for oral mucous membrane, Pregnancy Category: B
by topical administration, ADULT, spray the
appropriate volume to the desired area. Do
not exceed the recommended dose (see
Table above).valve delivers 10 mg lidocaine
(10 mg/dose) pump spray base.

Dose Adjustments:
Geriatric:
Administer reduced doses commensurate with
their age and physical status.

Precautions:
Spray:
Excessive dosage or short intervals between
doses may result in high plasma levels and
serious adverse effects.
Lidocaine spray should be used with caution in
patients with wounds or traumatized
mucosa in the region of proposed
application. A damaged mucosa may allow
increased absorption systemically.
Numbness of the site or the tongue and buccal
mucosa may occur.

See under Lidocaine in Anesthetics in the

chapter on Nervous System for more
information.

Adverse Drug Reactions:

Spray:
Local irritation at the site of application,
allergic reactions.
See under Lidocaine in the chapter on Nervous
System for more information.

Administration:
The spray nozzle is already bent to its final
appearance and no further actions should
be done before using the spray nozzle. The
nozzle must not be shortened otherwise the
spray function will be compromised.
Please read manufacturer’s instructions.

See under Lidocaine in Anesthetics in the

chapter on Nervous System for important
information on Precautions and Adverse
Drug Reactions.

Page | 328
VARIOUS
VARIOUS
ALL OTHER THERAPEUTIC
PRODUCTS
GENERAL ANTIDOTES
ACTIVATED CHARCOAL
Rx
Oral: USP grade powder, given as slurry
A fine, smooth, odorless, tasteless, black
powder, prepared from the
carbonization of organic matter.
Activated charcoal reduces drug or
poison absorption either by binding to
the drug in the GI tract or by interrupting
its entry into the enterohepatic
recirculation.
Indications: Gastrointestinal decontamination
for specific drug or poison ingestion
associated with significant risk of
toxicity; acute, oral poisoning
Contraindications: Bowel obstruction;
poisoning
By hydrocarbons (e.g., petroleum
distillates) with high potential for harm if
aspirated; poisoning by corrosive
substances; GI tract not anatomically
intact; unprotected airway
Dose:
Reduction of absorption, by mouth, ADULT and
CHILD >12 years, 50–100 g in 100–150
mL distilled water as a slurry given as a
single dose, as soon as possible after
ingestion of poison; CHILD 1–12 years,
25 g as a single
dose (50 g in severe poisoning) in 50–
100 mL distilled water; INFANT, 1 g/kg
as a single dose (maximum, 50 g) [NOTE:
May repeat lavage every 6 hours for 48–
72 hours. To produce effective
adsorption, a ratio of about 10-parts
activated charcoal to 1-part poison is
needed].
Active elimination, by mouth, ADULT, 50 g
every 4 hours (in case of intolerance, 25
g every 2 hours); CHILD >1 year, 25–50
g every 4–6 hours; INFANT, 1 g/kg every
4–6 hours.
Dose Adjustments:
In uremic adult patients:
By mouth, 20-50 g once daily.
Precautions:
WARNING: Electrolyte abnormalities
(hypernatremia, hypokalemia, and
hypermagnesemia) have been reported
to occur with the concomitant use of
cathartics, namely sorbitol, in the
charcoal.
Not generally recommended in children <1
year.
Monitor for active bowel sounds before
administering; drowsy, unconscious or
comatose patient (risk of aspiration –
ensure that airway is protected);
decreased peristalsis (administer within
1 hour of ingestion); caution during
multiple doses due to danger of
intestinal impaction (reduce initial dose
to half to prevent impaction; lavage
should be followed by sodium sulfate
cathartic).
Do not use for poisoning with the following
substances: alcohols (e.g., ethanol,
methanol), clofenotane (dicophane,
DDT), corrosive substances, cyanides,
malathion, metal salts, including those
of iron and lithium.
Adverse Drug Reactions:
Common: Black stools, blackening of teeth and
mouth; colicky abdominal pain
(discomfort, swelling), constipation,
nausea, vomiting.
Less Common: Diarrhea, hypotension.
Page | 329
VARIOUS
Rare: Bowel obstruction, charcoal embolism;
hypoglycemia, hypothermia, ALCOHOL, ETHYL
pneumonitis (due to aspiration). Rx
Drug Interactions:
Solution: 70%
Monitor closely with:
Laxatives (e.g., mannitol, sorbitol) – these may
A clear, aqueous solution of ethyl alcohol that
cause volume depletion and electrolyte
is used in the treatment of methanol
abnormalities.
toxicity due to its higher affinity to
alcohol dehydrogenase, thus inhibiting
Avoid concomitant use with:
the formation of toxic metabolites of
Anti-epileptics, oral contraceptives and other
methanol
charcoal interactants (e.g., digoxin,
paracetamol, furosemide, salicylates,
Indications: Antidote for methyl alcohol
sulfonylureas, sulfones, tetracyclines,
(methanol) poisoning
theophylline, tricyclic antidepressants) –
their absorption is reduced, and they
NOTE: Preferred antidote for methanol
may eventually be removed from
poisoning is fomepizole. Use only if
systemic circulation (may result to
fomepizole is unavailable.
treatment failure).
Food (e.g., milk, ice cream, sherbet) – this
Contraindications: Broken skin; patients who
decreases the adsorptive capacity of
have suffered severe burns when
activated charcoal.
diathermy has been preceded by
application of alcoholic skin
Administration: In preparing lavage, ensure
disinfectants.
that the patient is in Trendelenburg and
left lateral decubitus position.
Dose:
NOTE: IV administration is the preferred route.
Administer as a slurry (thick suspension) to
Continue therapy until methanol is no
increase adsorptive capacity; should not
longer detected or at <20 mg/dL AND
be administered with food due to
the patient is asymptomatic and
decreased efficacy; when given orally,
metabolic acidosis has been corrected.
the smallest dose should be given slowly
to avoid vomiting; adsorptive
Methanol poisoning, by IV injection, ADULT and
effectiveness is time-dependent
CHILD, initially 600–700 mg/kg
(greatest benefit is observed when
(equivalent to 7.6 to 8.9 mL/kg using a
administered within one hour after
10% solution); maintenance dose for
poison ingestion).
nondrinkers, 66 mg/kg per hour
NOTE: If the patient is conscious and
maintenance dose (equivalent to 0.83
cooperative, a slurry form of the
mL/kg per hour using a 10% solution);
activated charcoal may be orally
maintenance dose for chronic drinkers,
administered. But in cases where NGT
154 mg/kg per hour maintenance dose
may be obstructed, further dilution is
(equivalent to 1.96 mL/kg per hour
allowed.
using a 10% solution).
See under CPG on Common Poisoning for other
information.
NOTE: Goal of therapy is to maintain serum
alcohol levels >100 mg/dL.
Pregnancy Category: B
Dose Adjustment:
ATC Code: Not available
Hemodialysis:
Maintenance dose via IV administration:

Page | 330
VARIOUS
For nondrinkers, 169 mg/kg per hour
(equivalent to 0.22 mL/kg per hour ATROPINE
using a 10% solution). Rx
For chronic drinkers, 257 mg/kg per hour
(equivalent to 3.26 mL/kg per hour
Oral: 600 micrograms tablet (as sulfate)
using a 10% solution).
Inj.: 1 mg/mL ampul (IM, IV) (as sulfate)
Precautions:
An alkaloid from Atropa belladonna that
Diabetes;
competitively blocks acetylcholine action
Hepatic impairment or shock (use with
in central and peripheral muscarinic
caution);
autonomic receptors.
Children;
Pregnancy (crosses the placenta, enters fetal
Indications: Poisoning with organophosphate
circulation, and has teratogenic effects);
and n-methyl carbamate pesticides.
Lactation.
Contraindications: Hypersensitivity to atropine
Adverse Drug Reactions:
or any component of the formulation;
Common: Flushing, hypotension, agitation,
angle-closure glaucoma; severe
CNS depression, coma, disorientation,
inflammatory GI disease or GI
drowsiness, encephalopathy, headache,
obstruction; prostatic hypertrophy;
sedation, vertigo, hypoglycemia, gastric
prostatism and urinary obstruction;
irritation, nausea, vomiting, urinary
myasthenia gravis; thyrotoxicosis;
retention, nerve and tissue destruction,
organochlorine poisoning; pyloric
phlebitis, polyuria, intoxication
stenosis; poisoning caused by CNS
Rare: Seizure
adrenergic stimulants, phenothiazines,
tricyclic antidepressants and other
Drug Interactions: No information found.
anticholinergics.
NOTE: No contraindications exist in the
NOTE: Ethanol may interact with other
treatment of life-threatening
medications. See specific drug
organophosphate or carbamate
monographs for details on interactions
insecticides, and nerve agent poisoning.
with ethanol.
Dose:
Administration:
Organophosphate and carbamate poisoning,
For IV administration, administer via a central
by IM or IV injection (depending on the
vein as a 10% solution in D5W.
severity of poisoning), ADULT, 1-2 mg,
Administer the initial dose over 1 hour.
and CHILD, 20 micrograms/kg, repeated
For oral administration, dilute solutions to
every 5-10 minutes as necessary until
≤20%
full atropinization is observed (skin
concentration with water or juice and
becomes flushed and dry, pupils dilate
administer every hour. May also be
≥4 mm, pulse rate >120/minute, or, in
administered via nasogastric tube.
the elderly >70/minute, and hypoactive
Alcoholic beverages may be substituted,
bowel sounds); gradually decrease
but may contain different percentages of
interval of dosing and amount per dose
ethanol:
after 12-24 hours; continue for 2-3 days
Vodka ~40%
in carbamate poisoning and longer in
Wine ~12%
cases of organophosphates, or until the
Beer ~5%
patient can be transferred to a hospital.
Out-of-hospital management is not
recommended.

Pregnancy Category: C

Page | 331
VARIOUS
Dose Adjustment: Antacids – these may delay or reduce oral
Renal Impairment: absorption of atropine.
For mild-to-moderate renal impairment, dose Beta blockers (e.g., metoprolol) – their
reduction, or less frequent doses, after retention time may be increased by
initial atropinization is warranted (since atropine; it may also enhance their
atropine may be eliminated more dissolution and bioavailability.
slowly); for severe impairment, the Chlorpromazine – increased antimuscarinic
patient should be referred to a specialist. adverse effects (but reduced plasma
chlorpromazine concentration).
Precautions: Nitrates (e.g., isosorbide dinitrate) – atropine
Children; elderly; GI disorders (see may reduce the effects of sublingual
Contraindication); Down syndrome; tablets (failure to dissolve under the
prostatic enlargement; cardiac tongue due to dry mouth).
disorders; hypoxia; constipation,
delirium, tachycardia and fever from any Avoid concomitant use with:
cause (all these may be worsened by Anticholinergic drugs or other drugs with
atropine); pyrexia and in warm anticholinergic effects (see Appendix –
environments (monitor temperature and Table A) – these increase the
keep patients cool). therapeutic effect and risk of adverse
Pregnancy (crosses the placenta and may effects of atropine (including central
cause tachycardia); breastfeeding (small anticholinergic delirium); avoid these
amount present in milk; may cause combinations if possible (if required,
antimuscarinic effects in infants). monitor the patient, and reduce dose if
NOTE: Since atropine has a short duration, late necessary).
unopposed bradycardia may result. Anticholinesterases (e.g., neostigmine,
Therefore, close monitoring is pyridostigmine) – combining
necessary. anticholinergics with these drugs, which
increase acetylcholine concentration,
Adverse Drug Reactions: will antagonize the anticholinergic effect.
NOTE: Adverse effects following single or Digoxin – atropine may increase serum digoxin
repeated doses of atropine are most levels, resulting in enhanced actions and
often the result of excessive dosage. risk of toxicity.
Common: Blurred vision, constipation, Haloperidol – schizophrenic symptoms may
cycloplegia, delirium, dryness of mouth, worsen due to decreased plasma
nose and skin, difficulty in micturition concentration of haloperidol.
and swallowing, fever, flushing, Metoclopramide – atropine antagonizes the
mydriasis, palpitations, photophobia, effects of metoclopramide on GI activity.
thirst, transient bradycardia followed by Norepinephrine – enhanced pressor effect; its
tachycardia, urinary retention. reflex bradycardia is blocked by atropine.
Less Common: Agitation, arrhythmias, ataxia, Phenylephrine – atropine increases the risk of
confusion (in elderly), disorientation, severe hypertension with phenylephrine
excitement, headache, heat prostration, eye drops (use the combination
hyperpyrexia, hypertension, paralytic cautiously and monitor BP).
ileus, psychosis, rapid respiration, rash,
restlessness, vomiting. Administration: See under Clinical Practice
Rare: Angle-closure glaucoma, myocardial Guidelines – Common Poisoning.
infarction, seizures. NOTE: Parenteral drug products should be
inspected visually for particulate matter
Drug Interactions: and any possible discoloration prior to
Monitor closely with: administration; use only if solution is
Alcohol – enhanced CNS effects/CNS clear and seal intact.
depression.

Page | 332
VARIOUS
Pregnancy Category: C
ATC Code: Not available

PHYTOMENADIONE
Rx (PHYTONADIONE,
VITAMIN K)
Inj.: 10 mg/mL (as mixed micelle), 1
mL ampule (IM, IV)

10 mg/mL (as aqueous colloidal solution

with benzyl alcohol), 1 mL ampule (IM,
IV)

A fat-soluble vitamin that is an essential

cofactor in the synthesis of blood
coagulation factors: prothrombin (II), VII, IX,
X, and proteins C and S.

Indications: For warfarin and white or yellow

phosphorus “watusi” poisoning

Contraindications: Avoid IM if bleeding;

pregnancy (3rd trimester); it is not effective
in hereditary hypoprothrombinemia and
that caused by liver disease

Dose:
Warfarin-induced hypoprothrombinemia,
minor bleeding or not bleeding, by slow IV
injection, ADULT, 500 micrograms.
Warfarin-induced hypoprothrombinemia,
moderate hemorrhage, by IM injection,
ADULT, 10–20 mg.
Warfarin-induced hypoprothrombinemia,
severe hemorrhage, by slow IV injection,
ADULT, 5–10 mg.

Administration: administer by slow IV injection

over 30 seconds. Rapid infusion can cause
dyspnea, chest and back pain.
See Phytomenadione (Phytonadione, Vitamin
K1) under Vitamins in Chapter 1: Alimentary
Tract and Metabolism for other information.

Pregnancy Category: C; X in 3rd trimester or

near term

Page | 333
INTERIM PRACTICE GUIDELINES

Page | 334
 INTERIM PRACTICE GUIDELINES
USER GUIDE
The concept algorithm is defined as a step-by-step procedure
for solving a problem that contains conditional logic (‘if’/‘then’)
statements. Flow-chart algorithms or clinical algorithm maps are reported
to be uniquely suited for explicitly communicating conditional logic and
have become the main format for representing a clinical algorithm clearly
and succinctly. These algorithms are constructed with a flow of major
decisions from top to bottom and courses of action and alternatives from
left to right. Different types of boxes are used in algorithms:

• Clinical state boxes (rounded rectangle) define a clinical state or

problem which is to be addressed. They always appear at the
beginning and may also be used within the body of an algorithm.
These boxes may or may not have an entry path but have only
one exit path.

• Decision boxes (hexagon) contain statements that are phrased

as questions, punctuated with question marks (‘?’)

• Action boxes (rectangle) contain a clinical action, which is either

diagnostic or therapeutic. Algorithms usually end in a clinical
report. These boxes always have an entry path, but may not
have an exit.

• Link boxes (small oval) are used for continuity purposes for
algorithms that cannot fit on a single page.

These boxes are numbered sequentially from left to right and

top to bottom, except for link boxes.

Aside from the boxes which have been presented in these

Clinical Practice Guidelines, ‘Essential Practice Points’ have been
included to contain important details and information that are essential in
treating various diseases – both communicable and non-communicable.
Note that the texts within the practice points have been presented either

Page | 335
in green font color and enclosed in green-colored, round rectangles (for
the salient characteristics of the condition and the medicine, or for
recommended good practices), or in red font color and enclosed in red-
colored, round rectangles (for warnings and precautions).

Readers are enjoined to confirm the information contained

in the GUIDELINES by referring to additional sources, particularly
with regard to the most recent updates of the guidelines and new
medicines.

Page | 336
Page | 337
Page | 338
Page | 339
 Updated Interim Guidelines on the Management of
Community-Acquired Pneumonia (CAP) in
Immunocompetent Adults at the
Primary Care Level

Developed in collaboration with:

Dr. Eileen Aniceto, MD, FPCP, FPCCP

Dr. Rodolfo Pagcatipunan, FPCP, FPCCP
Philippine College of Chest Physicians

HIGHLIGHTS OF THE UPDATED GUIDELINES:

1. Once the diagnosis of Community-Acquired Pneumonia has been
adequately established, initial empiric antibiotic therapy should be
started.
2. For Low-Risk CAP patients without co-morbid illnesses, amoxicillin
remains to be the standard antibiotic of choice. The use of extended
macrolide may be considered.
3. The dosage of amoxicillin was increased to 1 gram thrice a day based
on the 2014 ARSP report.
4. For Low-Risk CAP patients with stable co-morbid conditions, β-Lactam
with β-Lactamase Inhibitor Combination (BLIC) or second-generation
cephalosporins with or without extended macrolides are
recommended.
5. Caution must be exercised with the use of azithromycin which can
cause abnormal electrical activity of the heart and fatal arrhythmias.
6. Fluoroquinolones are not recommended as 1st line antibiotics in CAP.
7. Oral 3rd generation cephalosporins are not recommended in the
treatment of Low-Risk CAP.
8. For patients who fail to show a response after 72 hours of empiric
antibiotic therapy, a full re-assessment must be done instead of
shifting to another antibiotic.

Page | 340
I. What is the approach to the diagnosis of CAP?

A. What is the definition of CAP?

1. CAP is an acute infection of the pulmonary parenchyma with

symptoms of acute illness accompanied by abnormal chest
findings. This is acquired in the community within 24 hours to
less than 2 weeks.

2. Its causative pathogens may be typical or atypical.

a. Typical pathogens: Streptococcus pneumoniae,

Haemophilus influenzae, and Moraxella catarrhalis present
with findings limited to the lungs.

b. Atypical pathogens: Mycoplasma pneumoniae,

Chlamydophila pneumoniae, and Legionella have
predilection for certain extrapulmonary organ systems (GI,
cutaneous).

B. How is CAP diagnosed?

1. By its clinical presentation:

a. There is no particular clinical symptom or abnormal finding

sufficient enough to distinguish CAP from other lower
respiratory tract infections.

b. The accuracy of predicting CAP using its common clinical

findings as bases is only between 60-76%.

c. However, a combination of the history and physical

examination findings can better predict the existence of
CAP. Prediction rules combining these parameters can be
utilized to better identify patients who may have pneumonia
and therefore need a chest x-ray.

d. The common presentation of CAP includes:

i. Acute cough

ii. Tachypnea (RR >20 breaths/minute)

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 iii. Tachycardia (cardiac rate >100/minute)

iv. Fever (temperature >37.8°C)

v. With at least one of the following abnormal chest

findings: diminished breath sounds, rhonchi,
crackles, or wheezes.

e. Important Note: There is no clinical feature that can reliably

distinguish typical from atypical pneumonia. The main
feature that may help to differentiate between the two is
the presence of extrapulmonary findings in pneumonia due
to atypical pathogens.

2. By Chest x-ray:

a. The chest x-ray SHOULD be done to confirm the diagnosis

of CAP. It is useful in the assessment of its severity,
differentiation of pneumonia from other diseases, and
prognostication.
i. Comparison of current versus previous chest x-
rays is recommended.
ii. A new parenchymal infiltrates in the chest x-ray is
the reference diagnostic standard for
pneumonia.

b. Recommended specific views:

Standard chest x-ray PA in full inspiration is the

recommended view.

The lateral view is optional with the left lateral view being
the preferred position since this will minimize the size of the
heart on the image.

In situations where PA view cannot be tolerated, AP upright

is acceptable.

c. Special situations:

i. When chest x-ray cannot be done or is not readily

available, for suspected CAP, empiric treatment
for lower respiratory tract infections similar to the

Page | 342
 out-patient managed low-risk recommendations
may be started among the following:

• Individuals without co-morbid conditions; or,

• Individuals with stable co-morbid conditions;
and,
• Individuals who present with normal vital signs
and PE findings,
• Where reliable follow-up can be ensured.

ii. However, a chest x-ray should still be pursued if there

is a poor response to treatment.

d. Important Note: There is no characteristic x-ray finding that

can predict the likely etiologic agent.

e. Important Note: An initial “normal” chest x-ray may connote

a radiographic lag phase. Chest radiographic findings also
usually clear more slowly than clinical findings and
repeated x-rays are generally not required.

f. In addition to disease progression, possible pulmonary

complications, such as pleural effusion (10.6%), empyema
(5.2%), lung abscess, or atelectasis should be assessed.

C. When are microbiologic studies necessary?

1. In low-risk CAP, microbiologic studies are optional.

2. Sputum gram stain and culture in low-risk CAP are generally not
done since the bacterial etiology is predictable with the most
common etiologic agents being the bacteria S. pneumoniae and
H. influenzae and the atypical pathogens being M. pneumoniae
and C. pneumoniae. There is also a low risk for mortality.

3. Sputum gram stain and culture are done in the following

situations:

a. Failure of response to previous antibiotics;

b. Clinical conditions where drug resistance may be an issue.

Page | 343
II. What is the approach to the treatment of CAP?

A. Determination of Risk Stratification of CAP:

1. A risk stratification based on the clinical presentation, status of

any co-morbid condition, and chest x-ray findings is used to
determine the site of care for the patient (see Table 1.1).

Sites of care are the: outpatient clinic, hospital/medical ward,

and ICU.

2. The risk stratification guidelines must be applied together with

the physician’s best clinical judgment and supplemented by
objective findings. The initial decision can change depending on
the clinical course.

Table 1.1. Clinical features in CAP according to risk categories.

LOW-RISK CAP
Presence of:
Stable vital signs:
RR<30 breaths/minute
PR <125 beats/minute
Temp. >36ᵒC or <40ᵒC
SBP >90 mmHg
DBP >60 mmHg
No altered mental status of
acute onset
No suspected aspiration
MODERATE-RISK CAP
Any of the following:
Unstable vital signs:
RR >30 breaths/minute
PR >125 beats/minute
Temp. >40°C or <36°C
SBP <90 mmHg
DBP <60 mmHg
Altered mental state of
acute onset
Suspected aspiration
HIGH-RISK CAP
Any of the criteria
under moderate-risk
CAP category PLUS
severe sepsis and
septic shock
With need for
ventilator support (e.g.,
mechanical ventilation,
non-invasive
ventilation)

No or stable co-morbid Decompensated co-

conditions morbid condition

Chest X-ray: Chest X-ray:

- Localized infiltrates - Multilobar infiltrates

Page | 344
- No pleural effusion or - Pleural effusion or
abscess abscess

3. Once the diagnosis of CAP has been adequately established,

initial antibiotic therapy should be started.

4. Patients with low-risk CAP can be managed as outpatient in the

absence of contraindications.

Clinically immunocompetent patients with CAP who have stable

or medically controlled co-morbid conditions (e.g., diabetes
mellitus, neoplasms, neurologic disease, congestive heart failure
Class I, coronary artery disease, COPD, asthma, chronic liver
disease, renal insufficiency, and chronic alcohol abuse) are also
classified under the low-risk category.

5. Those with moderate to high-risk CAP are hospitalized for closer

monitoring and/or parenteral therapy.

6. Important Note: Pneumonia itself can lead to worsening or

exacerbation of an underlying medical illness which may require
hospital admission regardless of the severity of pneumonia.

B. Initiation of Empiric Antimicrobial Therapy for CAP-LR:

1. In previously healthy adult patients with low-risk CAP, S.

pneumoniae and H. influenzae are the predominant etiologic
agents. Amoxicillin is considered the standard regimen for these
patients (see Table 1.2). The recommended dosage of amoxicillin
has been increased to 1 gram thrice a day. This was based on
the 2014 ARSP report that indicated the consistent level of
resistance of Streptococcus pneumoniae to the penicillins.

2. When atypical organisms are suspected (M. pneumoniae or C.

pneumoniae), extended macrolides (e.g., azithromycin,
clarithromycin) or azalides are given.

3. Warning! Azithromycin may cause abnormal electrical activity of

the heart and may cause fatal arrhythmias.

Page | 345
 Precautions for its use include cardiac conditions such as
prolongation of QT interval, other arrhythmias, and recent
myocardial infarction, presence of hypomagnesemia or
hypokalemia, use of other drugs for arrhythmia, and the elderly
who may be more susceptible to drug-induced QT prolongation
(please refer to the monograph on azithromycin for a complete
list of contraindications and precautions.

4. In patients with low-risk CAP and with stable co-morbid illnesses

or in those with recent antibiotic therapy, Gram-negative bacilli
may co-exist with the above pathogens so that β-lactamase
inhibitor combinations or BLIC (e.g., co-amoxiclav or amoxicillin-
clavulanic acid) or second-generation oral cephalosporins (e.g.,
cefuroxime axetil), with or without extended macrolides or
azalides (e.g., azithromycin and clarithromycin) are
recommended. The azalides are macrolide antibiotics that
contain nitrogen in the macrolide ring which imparts greater
stability to the molecule.

5. In patients hypersensitive to the β-lactams, the extended

macrolides may cover for S. pneumoniae and H. influenza.

6. The use of oral third-generation cephalosporin (e.g., ceftriaxone)

is not recommended for CAP-LR. It is recommended ONLY as a
step-down drug from an intravenous third-generation
cephalosporin.

7. Cotrimoxazole is not recommended for the treatment of CAP (see

Alert! below).

8. Fluoroquinolones are not recommended as 1st line therapy for

low-risk CAP (see Alert! below).

Antimicrobial Resistance Alert! Due to the continuing increase in

the rates of resistance of S. pneumoniae and H. influenzae to
cotrimoxazole, its use for CAP is not recommended.

Antimicrobial Resistance Alert!

Fluoroquinolones are not recommended as 1st line therapy
options for LR CAP. These are potential 2nd line agents for the
treatment of other infections.

Page | 346
 9. Duration of treatment:

For low-risk uncomplicated bacterial pneumonia, the duration is

5 – 7 days.

If azalides (macrolides) are used for S. pneumonia, the duration

of therapy is 3 – 5 days.

Table 1. 2. Empiric antimicrobial therapy for Low-Risk CAP.

RISK POTENTIAL EMPIRIC THERAPY

STRATIFICATION PATHOGEN
Low-risk CAP Streptococcus Previously healthy:
pneumoniae; Amoxicillin
Haemophilus Or
influenzae; Extended macrolides
Chlamydophila (suspected atypical pathogen)
pneumoniae;
Mycoplasma With stable co-morbid illness:
pneumoniae; β -lactam/β-lactamase inhibitor
Moraxella combination (BLIC)
catarrhalis; Or
Enteric Gram- Second-generation oral
negative bacilli cephalosporins +/– extended
(among those with macrolides
co-morbid illness)

Page | 347
 C. Usual recommended dosages of antibiotics in 50-60 kg
adults with normal liver and renal functions (see Table 1.3)

Table 1.3. Usual recommended dosage in 50-60 kg adult with normal liver and
renal functions.
ANTIBIOTICS FOR ADULT LOW- DOSAGE
RISK CAP (All antibiotics are taken orally))
• β-LACTAMS:
Amoxicillin 1 gram thrice a day for 5 – 7 daysa, b
• MACROLIDES:
Azithromycin dihydrate 500 mg once a day for 3 – 5 daysc
Clarithromycin 500 mg twice a day for 3 – 5 daysc
• β-LACTAM with β-LACTAMASE INHIBITOR COMBINATION (BLIC):
Co-amoxiclav (Amoxicillin- 625 mg thrice a day for 3 – 5 daysa
clavulanate) OR,
1 gram twice a day for 3 – 5 daysa
• 2nd GENERATION CEPHALOSPORINS

Cefuroxime axetil 500 mg twice a day for 5 – 7 daysa

a Duration recommended for low risk uncomplicated bacterial pneumonia
b Dose of amoxicillin was increased based on the 2014 ARSP report indicating
a consistent level of resistance of Streptococcus pneumoniae to penicillin
c Duration recommended if macrolides are used

D. How is the response to initial therapy assessed?

1. The following parameters are regularly monitored: temperature,

respiratory rate, heart rate, blood pressure, sensorium, and
when available, oxygen saturation.

2. Response to therapy is expected within 48-72 hours of initiating

antibiotic treatment. Parameters for improvement include:
decrease in fever episodes and body temperature, decrease in
the coughing, improvement in respiratory rate, and improvement
in WBC counts, among others.

E. What is done in case of failure to respond?

1. For patients who are not improving after 72 hours of empiric

antibiotic therapy, the following points are to be considered:

Page | 348
 a. The lack of response to seemingly appropriate
treatment should lead to complete reappraisal rather
than to using alternative antibiotics right away.
b. The clinical history, physical examination, and results of
available tests should be reviewed for possible
comorbidities or immune-compromising conditions.
The patient should be tested for resistance to the
current antibiotics or the presence of other pathogens
such as M. tuberculosis, viruses, parasites, or fungi.
Treatment should be revised according to culture
results.
c. Follow-up chest radiographs are recommended to
search for other conditions such as the extension to
uninvolved lobes.
d. Obtaining specimens for microbiological testing should
be considered.
e. Reasons for lack of response to antibiotic treatment
include the following:
• Correct organism but inappropriate drug
• Resistance of organism to the drug
• Wrong dose (e.g., in obese patient or
presence of fluid overload)
• Antibiotics not being given
• Correct organism and antibiotic but infection
is loculated
• Obstruction
• No identification of the causative organism
and empiric therapy is directed towards the
wrong organism
• Non-infectious cause
• Drug-induced fever
• Unrecognized concurrent infection.

2. Failure to respond to completed initial treatment should prompt

a referral to the higher level of healthcare facility or initiation of
extensive work-up to search for factors causing treatment failure
(e.g., sputum G/S and C/S).

Page | 349
III. What are the recommended preventive measures for CAP?

A. Vaccination

1. Influenza vaccination is recommended for individuals aged 55

years and above for the prevention of CAP. Influenza predisposes
individuals to bacterial CAP.
(Grade A Recommendation)

2. Pneumococcal vaccination is recommended for the prevention of

invasive pneumococcal disease in adults aged 55 years and
above. (Grade A Recommendation) PCV 13 is recommended to
be given first followed by pneumococcal polyvalent vaccine at
least one year later.
3. Vaccination may be given at any age for any of the following
individuals:
a. Persons >13 years old without history of varicella infection
or vaccination
b. Healthcare workers
c. Teachers of young children
d. Non-pregnant women of childbearing age
e. Persons with co-morbid conditions
f. International travelers
g. Military personnel.

B. Smoking Cessation

1. Smoking cessation is recommended for all persons with CAP

who smoke.
(Grade A Recommendation)
REFERENCE:
Joint Statement of the Philippine Society for Microbiology and Infectious
Diseases, Philippine College of Chest Physicians, Philippine Academy of
Family Physicians and Philippine College of Radiology, 2016, Philippine
Clinical Practice Guidelines on the Diagnosis, Empiric Management, and
Prevention of Community-acquired Pneumonia (CAP) in
Immunocompetent Adults 2016 Treatment Update, Makati City,
Philippines: Zurbano Publishing & Printing Corp., PPGG-ID Philippine
Society for Microbiology and Infectious Disease.

Page | 350
 Updated Interim Guidelines on the Management of
Pediatric Community-Acquired Pneumonia (pCAP)
among Children Aged 3 months to 18 years
at the Primary Care Level

Developed in collaboration with:

Philippine Academy of Pediatric Pulmonologists and Pediatric

Infectious Disease Society of the Philippines based on the
2016 PAPP Task Force on pCAP Update and the National
Antibiotics Guidelines 2019

HIGHLIGHTS OF THE UPDATED GUIDELINES:

1. The grading of recommendations with the corresponding levels of
evidence for the diagnostic and therapeutic guidelines are now based
on the grading developed by the Task Force on pCAP of the Philippine
Academy of Pediatric Pulmonologists or PAPP (refer to Table 4).
2. The key recommendations of the PAPP Task Force on pCAP that were
chosen to be included in this manual are mainly those that are
applicable for the primary care setting. However, recommendations
on pCAP C that can be treated in the out-patient clinic were
incorporated.
3. The determination of oxygen saturation with the use of pulse oximetry
was included since this will significantly improve diagnostic acumen
and assist in achieving an optimum therapeutic outcome.
Procurement of a pulse oximeter is highly recommended and its
correct use is mandatory.
4. The classification of community-acquired pneumonia is based on the
revised Risk Stratification for Pneumonia-Related Mortality where
pneumonia is diagnosed in the context of several signs and
symptoms.
5. The antibiotic regimen included in these guidelines is based largely on
the recommendations of the Task Force on pCAP of the PAPP and
recommendations stated in the National Antibiotic Guidelines.

Page | 351
 6. The key differences between the 2012 and the 2016 PAPP Guidelines
that are relevant for the Primary Care Manual are as follows:
a. predictors for detecting radiographic pneumonia include a
higher SaO2 and additional indexes;
b. addition of negative predictors for radiographic pCAP;
c. revised indications for requesting chest x-rays;
d. removal of diagnostic tests for tuberculosis;
e. an additional test to determine the necessity of antibiotic
administration for pCAP C;
f. addition of the definition of clinical stability; and,
g. zinc supplement may not be beneficial in reducing the clinical
impact of pneumonia.
7. For a patient with pCAP A or B due to typical pathogens and without
the intake of the previous antibiotic, amoxicillin remains to be the
initial choice. Co-amoxiclav and cefuroxime are alternative choices.
Azithromycin or clarithromycin may be given to a patient with known
hypersensitivity to amoxicillin or with clinical suspicion of atypical
organisms.
8. For pCAP A, B, C, or D in which a non-influenza virus is the suspected
pathogen, anti-viral drug therapy may not be beneficial

I. Who shall be considered as having Community-Acquired

Pneumonia?

A. A patient presenting initially with cough and/or respiratory

difficulty may be evaluated for the possible presence of
pneumonia (Recommendation Grade B2).

1. Pneumonia may be considered if any of the following

positive predictors of radiographic pneumonia is
present:

a. Tachypnea (age-specific as defined by the World

Health Organization – please refer to Table 4) in
a patient aged 3 months to above 5 years old;
b. Chest wall retractions in a patient aged 3 months
to above 5 years old;
c. Fever, grunting, wheezing, decreased breath
sounds, nasal flaring, cyanosis, crackles, or
localized chest findings at any age;

Page | 352
 d. Oxygen saturation (in case a pulse oximeter is
available) less than or equal to 94% at room air
in a patient aged 3 months to above 5 years with
the following conditions:
• absence of any co-morbid neurologic,
musculoskeletal or cardiac conditions
that may potentially affect
oxygenation; and,
• the pulse oximeter is correctly used.

2. Pneumonia may not be considered if any of the

following negative predictors of radiographic
pneumonia is present:

a. Absence of fever:
b. Absence of nasal flaring;
c. Absence of chest wall retractions;
d. Oxygen saturation (in case a pulse oximeter is
available) at room air greater than 94%.

B. Chest X-ray may be requested to determine the presence of

pneumonia in any of the following situations:

a. Dehydration in a patient aged 3 months to 5

years;
b. A high index of clinical suspicion.

Page | 353
Table 2.1. Grade recommendation with level of evidence (PAPP Task Force on
pCAP, 2016).

GRADE RECOMMENDATION DESCRIPTION OF EVIDENCE

STATEMENT
A A1 Should (or should not) be Definite evidence for benefit (or
recommended without benefit) based on at least
A2 Strong evidence exists to 1 metaanalysis of descriptive or
(or not to) be randomized controlled trials (RCT),
recommended but with or at least 2 separate descriptive
reservation or RCT s, with similar intervention,
study design, outcome, AND result
B B1 May (or may not) be Equivocal evidence for benefit (or
recommended without benefit) based on multiple
meta-analyses of descriptive or
RCT, or at least 2 separate
descriptive or randomized trials
with dissimilar intervention,
outcome, study design, OR results
B2 May (or may not) be
recommended but with
reservation
C C1 May (or may not) be Evidence for benefit (or without
recommended benefit) based on only 1
C2 May (or may not) be descriptive or RCT
recommended but with
reservation
D May (or may not) be Evidence for benefit (or without
recommended benefit) based on the consensus
opinion of at least three-fourths of
committee members of each
clinical question

II. Who will require admission?

A. Classification of Patient:

A patient may be classified as pCAP A, B, C, or D within 48

hours after consultation based on the Modified Risk
Classification for Pneumonia-Related Mortality (refer to
Table 2.2).

Page | 354
 B. Site-of-Care Treatment:

1. A patient classified as pCAP A or pCAP B may be

treated at the outpatient clinic.
2. A patient initially classified as pCAP A or pCAP B but is
not responding to current treatment after 48 hours
may be admitted.
3. A patient classified as pCAP C may be:
a. admitted to the regular ward; or,
b. managed initially on an out-patient basis
(Recommendation Grade C2) if all of the
following are not present on the initial
assessment:
i. age less than 2 years old;
ii. convulsion;
iii. chest x-ray with effusion, lung abscess, air
leak, or multilobar consolidation;
iv. oxygen saturation <95% at room air.
4. A patient classified as pCAP D may be admitted to a
critical care unit

III. What diagnostic aids are initially requested for a patient

classified as either pCAP A or pCAP B being managed in the
ambulatory setting?

A. The following may be requested:

1. Oxygen saturation using pulse oximeter when
available to assess gas exchange;
2. Chest x-ray PA-Lateral to confirm clinical suspicion of
necrotizing pneumonia, multilobar consolidation, lung
abscess, pleural effusion, pneumothorax, and
pneumomediastinum;
3. Sputum gram stain and/or aerobic culture and
sensitivity to determine microbial etiology (the patient
can be referred to a higher level of healthcare centers
or diagnostic laboratories for these tests).

B. The following may not be requested:

Page | 355
 1. Blood culture and sensitivity to determine microbial
etiology;
2. White blood cell count (WBC), C-Reactive Protein
(CRP), and Procalcitonin (PCT) as bases for initiating
antibiotic therapy.

Table 2.2. Revised risk classification for pneumonia-related mortality

(Recommendation Grade D).
RISK CLASSIFICATION1

PARAMETERS IDENTIFIED
AT pCAP A pCAP B pCAP C pCAP D
INITIAL SITE-OF-CARE
SEVERE or VERY SEVERE or
MODERATE HIGH
NON-SEVERE RISK RISK
RISK
A. CLINICAL PARAMETERS 2

1. Respiratory
Signs:
a. Retraction None Intercostal/ Supraclavicular/
Subcostal Intercostal/
Subcostal
b. Head None Present Present
bobbing
c. Cyanosis None Present Present
d. Grunting None None Present
e. Apnea None None Present
f. Tachypnea:
3 – 12 >50/min to >60/min to >70/min;
months 3 <60/min; <70/min;
1 – 5 years 3 >40/min to >50/min; >50/min;
<50/min;
>5 years >30/min to >35/min >35/min
<35/min
2. Central Nervous
System Signs:
a. Altered None Irritable Lethargic/
sensorium stuporous/
comatose
b. Convulsion None Present Present

Page | 356
3. Circulatory Signs:
a. Poor None Capillary refill Shock
perfusion > 3 sec 4
b. Pallor None Present Present
4. General
Considerations:
a. Malnutrition 5 None Mild Moderate Severe
b. Inability to No No Yes Yes
drink
c. Comorbid None Present Present Present
conditions

B. ANCILLARY PARAMETERS 6

pCAP A or pCAP B pCAP C pCAP D

1. Chest X-ray
findings of:
Effusion, None Present Present
abscess, air leak
or lobar
consolidation
2. Oxygen
saturation at 95% 91% to 94% <90%
room air using
pulse oximetry

1 To classify to a higher risk category, at least 2 variables (i.e., clinical and

diagnostic aid) should be present. In the absence of diagnostic aid
variables, the clinical variables will suffice.
2 Risk factors for mortality based on evidence and/or expert opinion among
members of the 2016 PAPP Task Force on pCAP.
3 WHO age-specific criteria for tachypnea for children under 5 years old.
4 Procedure for determining capillary refill: press the fingernail firmly then
release and note for return of color indicating refill. The absence of refill
after > 3 seconds from release may indicate the presence of perfusion
problems.
5 Weight for Height (WFH) SD score < -2 moderate; SD score < -3 severe,
from WHO Management of Severe Malnutrition: a Manual for Physicians
and other Health Workers, Geneva, WHO, 1999.
6 Chest x-ray and pulse oximetry are desirable variables but not necessary
as determinants of admission
at site-of-care.

Page | 357
 IV. When is an antibiotic recommended?

A. For pCAP A or pCAP B, an antibiotic may be initiated if a

patient is:
1. Beyond 2 years of age (Recommendation Grade D);
2. With high-grade fever without wheeze
(Recommendation Grade D).

B. For pCAP C, empiric antibiotic may be started if any of the

following is present:
1. Persistent high-grade fever without wheeze
(Recommendation Grade D);
2. White blood cell count (Recommendation Grade B2)
greater than 15,000;
3. Alveolar consolidation on chest x-ray
(Recommendation Grade B2).

C. For pCAP D, refer urgently to a hospital with adequate

facilities.

V. What empiric treatment should be administered if a

bacterial etiology is strongly considered?

A. For patients diagnosed to have pCAP A or pCAP B due to a

bacterial pathogen and in whom antibiotics were not
previously given, regardless of immunization status against
Hemophilus influenzae type B or to Streptococcus
pneumonia, the following are recommended:

1. Amoxicillin trihydrate may be given.

• It may be given at 40 – 50 mg/kg/day, maximum
dose of 1,500 mg/day, in 3 divided doses;
• It may be given for 5 to 7 days.

2. Alternative antibiotics to amoxicillin include:

a. Co-amoxiclav at a dose of 40 – 50 mg/kg/day per
orem divided into 2 doses given every 12 hours
(14:1 preparations) for 5 – 7 days; or,
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 b. Cefuroxime at a dose of 20 – 30 mg/kg/day per
orem divided into 2 doses given every 12 hours for
5 – 7 days.
3. If with known allergy or hypersensitivity to amoxicillin,
consider giving macrolides, either:
a. Clarithromycin at 15 mg/kg/day with a maximum
dose of 1,000 mg /day in 2 divided doses for 7
days, may be given; or,
b. Azithromycin at 10 mg/kg/day once daily for 3
days, or at 10 mg/kg/day at Day 1 then 5
mg/kg/day at Days 2-5, with a maximum dose of
500 mg/day, may be given.

4. The National Antibiotic Guidelines Committee also

recommends the following regimen for children aged > 5
years old and for adolescents who present with complaints
related to slowly progressive systemic symptoms over 3 to
7 days, with malaise, pharyngitis, and headache, followed
by a cough that is irritative and non-productive (lasting for 2
– 4 weeks) and in whom the physical examination may
show rales, rhonchi, and wheezes in a child who does not
appear ill (“walking pneumonia”):
a. Erythromycin at 50 mg/kg per orem every 6 – 8
hours daily for 10 – 14 days; or,
b. Clarithromycin suspension at 15 mg/kg divided
every 12 hours for 10 days; or,
c. Azithromycin at 10 mg/kg/day per orem daily, or,
10 mg/kg/day on day 1 then 5 mg/kg/day per
orem on days 2 – 5.

5. The parents and caregivers must be instructed to

closely observe the infant or child for signs of improvement,
failure to improve, or deterioration. The patients must be
brought back to the center or the physician or healthcare
personnel for re-assessment after 2 to 3 days or anytime
deterioration is noted.

6. In case of non-response to initial treatment within 48 to

72 hours, the patient must be referred to a higher level of
healthcare center for further diagnostic evaluation (see
section VIII) and therapeutic intervention. While awaiting

Page | 359
 transport to the center, the following may be employed by
the physician:
a. If initially started on Amoxicillin, shift to Co-
Amoxiclav at 90 mg/kg per orem (amoxicillin
component) in divided doses given every 12 hours
daily; or,
b. If initially started on Co-Amoxiclav, have the patient
admitted for intravenous antibiotics;
c. May also consider adding an oral macrolide;
d. Consider other diagnosis (refer to Section VIII).

B. For a patient classified as pCAP C who can tolerate oral

feeding and who does not require oxygen support, the
following may be given: Amoxicillin at 90 mg/kg/day with a
maximum dose of 1,500 mg/day in 3 divided doses for 7
days.

The parents and caregivers are likewise instructed to closely

observe the infant or child for signs of deterioration or
failure to improve. The patients must be brought back to
the center or the physician or healthcare personnel for re-
assessment after 2 to 3 days. In case of failure to respond
to the initial treatment, the patient must immediately be
referred to a higher level center for further diagnostic
evaluation (see Section VIII) and therapeutic intervention.

C. For a patient classified as pCAP D, urgent referral to a

hospital with adequate facilities and admission to a critical
care unit must be done.

D. For a patient suspected to have community-acquired

methicillin-resistant Staphylococcus aureus, urgent referral
to a hospital must be done.

E. Ancillary treatment may be given (refer to Section IX).

VI. What treatment should be initially given if a viral etiology is

strongly considered?

A. For pCAP A, B, C, or D in which a non-influenza virus is the

suspected pathogen, anti-viral therapy may not be
beneficial (Recommendation Grade D).
Page | 360
 B. For pCAP C or pCAP D, antiviral drug therapy for clinically
suspected or laboratory-confirmed influenza virus to reduce
the risk for pneumonia may not be beneficial.

C. However, for pCAP C or pCAP D, antiviral drug therapy for

clinically suspected or laboratory-confirmed influenza virus
to reduce time to symptom resolution may be beneficial
(Recommendation Grade B1).

Oseltamivir may be started within 48 hours from onset of

influenza-like symptoms at the following doses:
1. for infants 3-8 months old, give 3 mg/kg per dose
twice daily x 5 days;
2. for infants 9-11 months old, give 3.5 mg/kg per dose
twice daily x 5 days;
3. for > 12 months old:
a. for body weight < 15 kg, give 30 mg twice daily x
5 days,
b. for >15 – 23 kg give 45 mg twice daily x 5 days,
c. for > 23-40 kg, give 60 mg twice daily for 5 days,
d. for > 40 kg, give 75mg twice a day for 5 days.

D. Oseltamivir or zanamivir may be beneficial to reduce the

burden of pneumonia during a flu epidemic.

E. Symptomatic and ancillary treatment may be beneficial.

VII. When can a patient be considered as responding to the

current therapeutic management?

A. Good clinical response to current therapeutic management

may be assessed based on achieving clinical stability that is
sustained for the immediate past 24 hours.

B. For pCAP A or pCAP B, clinical stability may be assessed

within 24-48 hours after the consultation if the cough has
improved or body temperature (measured in degree Celsius)
has returned to normal.

Page | 361
 C. For pCAP C treated as an out-patient, clinical stability may be
assessed within 24-48 hours if any of the following
physiologic parameters have improved significantly or has
returned to normal:
1. The respiratory rate at full minute based on the WHO-
defined, age-specific values for tachypnea (refer to
Table 5);
2. Oxygen saturation at room air using pulse oximeter
when available;
3. Body temperature (measured in degree Celsius);
4. The cardiac rate at full minute based on the Pediatric
Advanced Life Support age-based values; or,
5. Work of breathing.

D. Good clinical response to current therapeutic management

may not require chest x-ray or complete blood count to
document treatment success at end of treatment.

VIII. What should be done if a patient is not responding to the

current therapeutic management?

A. If a patient with pCAP A or pCAP B is not improving or is

clinically worsening within 72 hours after initiating a
therapeutic intervention (regarded as treatment failure),
diagnostic evaluation to determine if any of the following is
present may be considered:

1. Co-existing, or another etiologic agent;

2. Etiologic agent resistant to the current antibiotic, if
being given;
3. Other diagnosis:
a. pneumonia-related complication (e.g., necrotizing
pneumonia, pleural effusion);
b. asthma;
c. pulmonary tuberculosis.

B. If a patient with pCAP C treated as an out-patient is not

improving or is clinically worsening within 48 hours after
initiating a therapeutic intervention (regarded as treatment
failure),

Page | 362
 diagnostic evaluation to determine if any of the following is
present may be considered:
1. Co-existing, or another etiologic agent;
2. Etiologic agent resistant to the current antibiotic, if
being given;
3. Other diagnosis:
a. pneumonia-related complication (e.g., acute
respiratory failure, pneumothorax, lung
abscess, necrotizing pneumonia, pleural
effusion);
b. asthma; or,
c. pulmonary tuberculosis.

IX. What ancillary treatment can be given?

A. During the course of illness for pCAP A or pCAP B, the

following may be beneficial:
1. Oral steroid in a patient with co-existing asthma;
2. Bronchodilator in the presence of wheezing.

B. During the course of illness for pCAP A or pCAP B, the

following may not be beneficial:
1. Cough preparation or parenteral steroid in a patient
without asthma;
2. Elemental zinc, vitamin D3, and probiotic.

X. How can pneumonia be prevented?

A. The following are beneficial in reducing the burden of

hospitalization because of pneumonia:
1. Conjugated vaccine (PCV 10 or 13) against
Streptococcus pneumoniae (refer to recommended
Vaccination Schedule).
2. Vaccine against Hemophilus influenzae type B,
Influenza sp (refer to recommended Vaccination
schedule).
3. Breastfeeding;
4. Avoidance of cigarette smoke.

B. The following are not beneficial in reducing the clinical

impact of pneumonia:

Page | 363
 1. Zinc supplement;
2. Vitamin D.

REFERENCES:

PAPP 2016 Task Force on pCAP, Philippine Academy of Pediatric

Pulmonologists.2016. PAPP Perspective. PAPP Update in the
Evaluation and Management of Pediatric Community-Acquired
Pneumonia. Kalayaan Avenue: Quezon City.

National Antibiotics Guidelines Committee. National Antibiotics

Guidelines 2019. Pharmaceutical Division, Department of
Health, Quezon City.

Page | 364
 Clinical Practice Guidelines on the Diagnosis
and Management of Urinary Tract Infections in
Adults at the Primary Care Level
Based on the 2013 and 2015 Clinical Practice
Guidelines for Urinary Tract Infections
and the National Antibiotics Guidelines 2019

I. Uncomplicated Urinary Tract Infection

A. Acute Uncomplicated Cystitis (AUC) in Women

1. What is the approach to the diagnosis of AUC?

• Clinically, among premenopausal, non-pregnant and

otherwise healthy women, acute uncomplicated cystitis
(AUC) is suspected when there is acute onset of dysuria,
frequency, urgency, and gross hematuria, and absence of
vaginal discharge.
• Urinalysis is not necessary to confirm the diagnosis of AUC
in women presenting with one or more of the above
symptoms of urinary tract infection (UTI) in the absence of
vaginal discharge and complicating conditions enumerated
in Table 6.
• Women presenting with urinary symptoms plus vaginal
discharge should undergo further evaluation to search for
other disease conditions.
• Conditions that define complicated urinary tract infection
(cUTI) must be absent as obtained in history taking (see
Table 3.1).
• Common pathogens are E. coli (75-90%) and S.
saprophyticus (5-15%).

Page | 365
Page | 366
 Table 3.1. Conditions that define complicated UTI in women.

Presence of structural abnormalities causing urinary stasis and obstruction

of the genitourinary tract:
• Obstructive uropathy due to carcinoma, bladder outlet obstruction,
calculus, or cystocoele
• Urethral or ureteric strictures, tumors, calculi, and other urologic
anatomic abnormalities
• Polycystic kidney disease
Functional abnormalities that affect normal urine outflow:
• Incomplete emptying of the bladder with > 100 mL retained urine
post-voiding
• Vesico-ureteral reflux
• Neurogenic bladder, spina bifida, multiple sclerosis
Conditions that interfere with host defense mechanisms:
• Azotemia due to intrinsic renal diseases
• Renal transplantation
• Diabetes mellitus
• Immunosuppressive conditions – e.g., febrile neutropenia,
myeloproliferative disorders, chemotherapy
Iatrogenic conditions:
• Presence of in-dwelling urinary catheter or intermittent
catheterization, stents
• Peri-operative or post-operative UTI
• Surgically created abnormalities
Pathogen-related complicating factors:
• UTI caused by unusual pathogens (M. tuberculosis, Candida spp)
• UTI caused by antibiotic-resistant or multi-drug resistant organisms
(MDRO)
Others:
• Chemical or radiation injuries of the uroepthelium
• Urosepsis or severe pyelonephritis

2. What is the approach to the treatment of AUC?

i. Are laboratory tests necessary before initiation of antibiotic

therapy?

• Empiric antibiotic treatment is the most cost-effective

approach in the management of AUC.
• Pre-treatment urinalysis and urine culture and
sensitivity are not recommended.

Page | 367
 • Standard urine microscopy and dipstick leukocyte
esterase (LE) and nitrite tests are not prerequisites for
treatment.

ii. What antibiotics can be used for AUC at the Primary

Healthcare Level?

• The selection of the antibiotics recommended for use

in AUC (see Table 3.2) was based on:

o Efficacy in terms of clinical cure, cost-

effectiveness, safety, and tolerability were
considered in the choice of antibiotics.
o Low propensity to cause collateral damage and
local susceptibility rates were given greater
weight in the choice of antibiotic
recommendations.

Collateral damage is the “ecological adverse

effect” of antibiotic therapy. Such adverse
effects include the selection of drug-resistant
organisms and colonization or infection with
multi-drug resistant organisms.

Table 3.2. Recommended antibiotics for acute uncomplicated cystitis in non-

pregnant women in the primary care facility.
Antibiotics Recommended dose and duration
First Line Nitrofurantoin 100 mg 4x a day for 5 days per
macrocrystals orem

Second Co-amoxiclav 625 mg 2x a day for 7 days per

Line (Amoxicillin- orem
clavulanate)

Cefuroxime axetil 250 mg 2x a day for 7 days per

orem

iii. What are the recommendations with regard to the specific

utilization of antibiotics in the treatment of AUC?

Page | 368
 The following are the strong recommendations based on
high quality of evidence:

i. Nitrofurantoin monohydrate/macrocrystals (100 mg

twice daily for five days) is recommended as the first-
line treatment for acute uncomplicated cystitis due to
its high efficacy, minimal resistance, minimal adverse
effects, low propensity for collateral damage, and
reasonable cost. However, the nitrofurantoin
monohydrate/macrocrystal formulation is not locally
available. Thus, the locally available nitrofurantoin
macrocrystal formulation 100 mg is recommended,
but it should be given four times a day for five days.

Antimicrobial Resistance Alert!

Ampicillin or amoxicillin should not be used for
empirical treatment of AUC given the relatively poor
efficacy and the very high prevalence of antimicrobial
resistance to these agents worldwide.

Antimicrobial Resistance Alert!

Trimethoprim-sulfamethoxazole 800/160 mg twice a
day for three days should be used ONLY for culture-
proven susceptible uropathogens due to the high
prevalence of local resistance and high failure rates.

Antimicrobial Resistance Alert!

Fluoroquinolones should not be used as a first-line
drug for acute uncomplicated cystitis despite their
efficacy due to its high propensity for collateral
damage.

ii. Beta-lactam agents, including co-amoxiclav

(amoxicillin-clavulanate), and cefuroxime are
appropriate alternative choices for therapy when the
primary recommended agents cannot be used.

iii. The recommended treatment for otherwise healthy

elderly women with AUC is the same.

Page | 369
 3. What is the course of action for patients who do not respond to
treatment?

i. Patients whose symptoms worsen or do not improve after

completion of treatment should have a urine culture done,
and, the antibiotic should be empirically changed pending
the result of sensitivity testing.

ii. Patients whose symptoms fail to resolve after treatment

should be managed as complicated UTI.

4. Are post-treatment diagnostic tests needed in patients who

respond to treatment?

Routine post-treatment urine culture and urinalysis in patients

whose symptoms have completely resolved are NOT
recommended as it does not provide any added clinical benefit.

B. Acute Uncomplicated Pyelonephritis (AUP)

1. What is the approach to the diagnosis of AUP?

i. Acute uncomplicated pyelonephritis (AUP) is suspected in

otherwise healthy women with no clinical or historical
evidence of anatomic or functional urologic abnormalities,
who present with the classic syndrome of fever (T ≥38°C),
chills, flank pain, costovertebral angle tenderness, nausea,
and vomiting, with or without signs and symptoms of lower
urinary tract infection.

ii. Laboratory findings include pyuria (≥5 WBC/HPF of

centrifuged urine) on urinalysis and bacteriuria with counts
of ≥10,000 CFU of uropathogen/mL on urine culture.
(Strong recommendation, moderate quality of evidence)

iii. What pre-treatment diagnostic tests are necessary?

i. Urinalysis and Gram-stain are recommended. Urine

culture and sensitivity tests should also be performed
routinely to facilitate the cost-effective use of
antimicrobial agents and because of the potential for
serious sequelae if an inappropriate antimicrobial
agent is used. (Strong recommendation, High quality
of evidence)
Page | 370
 ii. Blood cultures are not routinely recommended except
in patients with signs of sepsis (see Table 3.3). (Strong
recommendation, High quality of evidence)

Table 3.3. Signs of sepsis.

Any two of the following:

1. Temperature >38°C or <36°C
2. Leukopenia (WBC <4,000) or leukocytosis (WBC >12,000)
3. Tachycardia (HR >90 beats/minute)
4. Tachypnea (RR >20 breaths/minute or PaCO2 <32 mmHg)
5. Hypotension (SBP <90 mmHg or >40 mmHg drop from
baseline)

iii. Common pathogens: As for AUC, E. coli is predominant

as well as other Enterobacteriaceae.

iv. Biomarkers (procalcitonin and C-reactive protein) are

not recommended since they are not clinically useful
in determining the need for admission or in predicting
adverse outcomes, such as recurrence and prolonged
hospitalization.

2. What are the indications for admission to the hospital?

i. Inability to maintain oral hydration or take medications;

ii. Concern about compliance;
iii. Presence of possible complicating conditions;
iv. Severe illness with high fever, severe pain, marked debility,
and signs of sepsis.

3. What is the approach to the treatment of AUP?

i. What antibiotics can be used for the treatment of AUP?

• The selection of the antibiotic regimen found to be

effective in AUP (see Table 3.4) were based on:

o Efficacy, cost-effectiveness, safety, tolerability,

local susceptibility; and
Page | 371
 o A low propensity for collateral damage

Table 3.4. Empiric treatment regimens for acute uncomplicated pyelonephritis in

non-pregnant women in the primary care facility.

Antibiotic (Oral) Dose, Frequency, and Duration

First Line Ciprofloxacin 500 mg twice a day for 7-10 days

Cefuroxime axetil 500 mg twice a day for 14 days

Second
Line Co-amoxiclav
(Amoxicillin-clavulanate) 625 mg thrice a day for 14 days
when GS shows gram-
positive organisms

ii. What are the recommendations with regard to the specific

utilization of other antibiotics in the treatment of AUP?

Quinolones are recommended as the first-line treatment

only for acute uncomplicated pyelonephritis not requiring
hospital admission (Strong recommendation, High quality
of evidence).

The following are strong recommendations based on

moderate quality of evidence:

Antimicrobial Resistance Alert!

The aminopenicillins (ampicillin or amoxicillin) and
first-generation cephalosporins are not
recommended for AUP because of the high prevalence
of resistance and increased recurrence rates in
patients given these beta-lactams.

Antimicrobial Resistance Alert!

Because of high resistance rates to cotrimoxazole,
this drug is not recommended for empiric treatment
of AUP, but it can be used when an organism is
susceptible to urine culture and sensitivity.

Page | 372
 i. In patients not requiring hospital admission, an initial
single IV or IM dose of ceftriaxone or aminoglycoside
may be considered followed by any of the oral
antibiotics recommended in Table 3.4.

Antibiotic regimens recommended in this situation are

as follows:
• Ceftriaxone at 1 – 2 grams IV as initial
single dose; or,
• Amikacin at 15 mg/kg as initial single
dose; or,
• Gentamicin at 3 – 5 mg/kg as initial single
dose +/- Ampicillin.

The initial parenteral antibiotic will be followed by any

of the oral antibiotics in Table 9.

ii. For suspected enterococcal infection, ampicillin may

be combined with an aminoglycoside (weak
recommendation based on low quality of evidence).

4. What is the role of radiologic imaging in the management of AUP?

i. The following are strongly recommended based on

moderate quality of evidence:

• Routine urologic evaluation and routine use of

imaging procedures are not recommended.
• Consider early radiologic evaluation if the patient has
a history of urolithiasis, urine pH ≥7.0, or renal
insufficiency.

ii. The following may also be considered (only weakly

recommended due to low quality of evidence):

• Consider radiologic evaluation if the patient remains

febrile within 72 hours of treatment or if symptoms
recur to rule out the presence of nephrolithiasis,
urinary tract obstruction, renal or perinephric
abscesses, or other complications of pyelonephritis.
• Obtain urologic consultation if radiologic workup
shows abnormalities.

Page | 373
 5. What are the follow-up laboratory tests needed?

The following may also be considered (weakly recommended due

to low quality of evidence):

a. In patients who are clinically responding to therapy (usually

apparent in <72 hours after initiation of treatment), a
follow-up urine culture is not necessary.
b. Routine post-treatment cultures in patients who are
clinically improved are also not recommended.
c. In women whose symptoms do not improve during therapy
and in those whose symptoms recur after treatment, a
repeat urine culture and sensitivity test should be
performed.

6. What is the course of action in patients with recurrence of

symptoms?

The following may also be considered (weakly recommended due

to low quality of evidence):

a. Recurrence of symptoms requires antibiotic treatment

based on urine culture and sensitivity test results in
addition to assessing for underlying genito-urologic
abnormality.
b. The duration of re-treatment in the absence of a urologic
abnormality is two weeks.
c. For patients whose symptoms recur and whose culture
shows the same organism as the initial infecting organism,
a four- to six-week regimen is recommended.

Table 3.5. GRADE System: strength of recommendation, and quality of

evidence.

Category / Grade Definition

RECOMMENDATION
Strong Desirable effects (benefits) clearly
outweigh the undesirable effects (risks)
Conditional Desirable effects probably outweigh the
undesirable effects but the
recommendation is applicable only to a
specific group, population or setting; or

Page | 374
 the benefits may not warrant the cost or
resource requirements in all settings.
Weak Desirable and undesirable effects closely
balanced or uncertain; new evidence may
change the balance of risk to benefit.
No Further research is required before any
recommendation recommendation can be made.

QUALITY OF EVIDENCE
High Consistent evidence from well-performed
RCTs or exceptionally strong evidence
from unbiased observational studies;
further research is very unlikely to change
confidence in the estimate of the effect.
Moderate Evidence from RCTs with important
limitations or moderately strong evidence
from unbiased observational studies;
further research is likely to have an
important impact on confidence in the
estimate of the effect.
Low Evidence for ≥1 (one) critical outcome
from observational studies, from RCTs
with serious flaws, or from indirect
evidence; further research is very likely to
have an important impact on the estimate
of effect and is likely to change the
estimate.
Very Low Evidence for ≥1 (one) critical outcome
from unsystematic clinical observation or
very indirect evidence; any evidence of
effect is very uncertain.

Page | 375
II. Asymptomatic Bacteriuria in Adults

Summary of Recommendations

1. When is asymptomatic bacteriuria diagnosed?

a. Asymptomatic bacteriuria is defined as the presence of

bacteria in the urine without associated clinical signs and
symptoms of UTI.
b. All diagnoses of asymptomatic bacteriuria (ASB) should be
based on results of urine culture specimens that are
collected aseptically and with no evidence of
contamination.
c. For asymptomatic women, bacteriuria is defined as 2
consecutive voided urine specimens with isolation of the
same bacterial strain in quantitative counts > 100,000
cfu/mL. (Strong recommendation, high quality of evidence)
d. In men, a single, clean-catch voided urine specimen with 1
bacterial species isolated in a quantitative count > 100,000
cfu/mL identifies bacteriuria. (Strong recommendation,
high quality of evidence)
e. In both men and women, a single catheterized urine
specimen with 1 bacterial species isolated in a quantitative
count > 100,000 cfu/mL identifies bacteriuria. (Strong
recommendation, high quality of evidence)

2. What are the indications for screening and treatment of

asymptomatic bacteriuria?

a. Screening and treatment are recommended in the following

to prevent bacteremia and sepsis:
• Patients who will undergo genitourinary
manipulation or instrumentation (likely to cause
mucosal bleeding).
• All pregnant women. (Strong recommendation, high
quality of evidence)
b. The choice of antibiotics depends on culture results. A
seven-day regimen is recommended. (Strong
recommendation, low quality of evidence)
c. For specific antibiotic recommendations for ASB in
pregnancy, see the following Section on UTI in Pregnancy.
d. Antibiotics do not decrease asymptomatic bacteriuria nor
prevent subsequent development of UTI.
Page | 376
 3. Who should NOT be screened and treated for asymptomatic
bacteriuria?
a. Routine screening and treatment for ASB are not
recommended for healthy adults. (Strong recommendation,
low quality of evidence)
b. Likewise, periodic screening and treatment for ASB are not
recommended in the following:
• Patients with diabetes mellitus
• Elderly patients
• Patients with in-dwelling catheters
• Solid organ transplant patients
• People living with Human Immunodeficiency Virus (HIV)
• Spinal cord injury patients
• Patients with urologic abnormalities.

4. What is the optimal screening test for asymptomatic bacteriuria?

a. Screening by urine culture is recommended. (Strong
recommendation, high quality of evidence)
b. In the absence of facilities for urine cultures, the following
findings using 2 consecutive midstream urine samples can
be utilized to screen for Asymptomatic Bacteriuria:
i. Significant pyuria (> 10 wbc/ hpf); or,
ii. Positive gram stain of unspun urine (> 2
microorganisms/ oil immersion field or oif).
c. Urine culture and sensitivity testing are not necessary when
a urinalysis is negative for pyuria or urine gram stain is
negative for organisms.
d. Pyuria accompanying asymptomatic bacteriuria is not an
indication for antimicrobial treatment among patients for
whom screening and treatment are not recommended.

III. Urinary Tract Infections in Pregnancy

A. Asymptomatic Bacteriuria in Pregnancy

1. When is asymptomatic bacteriuria in pregnancy diagnosed?

• Asymptomatic bacteriuria in pregnancy is the presence of

>100,000 CFU/mL of the same uropathogen in two
consecutive midstream urine specimens, or >100 CFU/mL

Page | 377
 of a single uropathogen in one catheterized urine
specimen, in the absence of symptoms attributable to
urinary tract infection.
• In situations or settings where obtaining two consecutive
urine cultures are not feasible or difficult, one urine culture
is an acceptable alternative for the diagnosis of ASB in
pregnancy (weak recommendation, low quality of
evidence).

2. Do all pregnant women have to be screened for ASB?

• All pregnant women must be screened for ASB on their

prenatal visit between the 9th to 17th weeks, preferably on
the 16th week age of gestation.

3. What is the optimal screening test for ASB in pregnancy?

• A standard urine culture/ susceptibility test of clean-catch

midstream urine is the test of choice in screening for
asymptomatic bacteriuria.
• If the urine culture is not available, an initial gram stain of
uncentrifuged urine (more than one organism per oil
immersion field) is recommended for screening for ASB.
Dipslide culture technique may be used as an alternative to
urine culture in settings where this is available.
• Urinalysis is inadequate for ASB screening and thus, is not
recommended as the initial screening test. Urine dipsticks
for leucocyte esterase and/or nitrite tests are not
recommended for screening also.

4. What is the effective treatment for ASB in pregnancy?

• Antibiotic treatment for asymptomatic bacteriuria is

indicated to reduce the risk of acute cystitis and
pyelonephritis in pregnancy as well as to reduce the risk of
low birth weight neonates and preterm infants.

• It is recommended that antibiotic treatment be initiated

upon the diagnosis of ASB in pregnancy. The choice
depends on the culture/ susceptibility test of the urine
isolate. Among the antibiotics that can be used are
cefalexin, cefuroxime, co-amoxiclav, and nitrofurantoin.

Page | 378
 Please refer to the following tables for the recommended
antibiotics and the dosages and duration of treatment.

Important Note: there are precautions for co-amoxiclav and

nitrofurantoin as stated in the subsequent tables.

* Cotrimoxazole should be avoided in the 1st and 3rd

trimesters.
* Nitrofurantoin must be used with caution (not for near
term).

• Duration of treatment depends on the antibiotic used, but,

short course (7 days) treatment is preferred over single-
dose regimens.

• Do follow-up cultures one week after completing the course

of treatment (Grade C).

Table 3.6. Recommended antibiotics for asymptomatic bacteriuria in pregnancy

in the primary care facility.
ANTIBIOTICS RECOMMENDED FDA PREGNANCY RISK
(In pregnancy) DOSE & CATEGORY
DURATION

Cephalexin 500 mg 2x a day B

for 7 days

Cefuroxime axetil 500 mg 2x a day B

for 7 days

Co-amoxiclav 625 mg 2x a day B

(Amoxicillin- for 7 days Caution!
clavulanate) Avoid in those at risk for pre-
see cautions term labor because of the
potential for neonatal
necrotizing enterocolitis.

Nitrofurantoin 100 mg 4x a day B

macrocrystal for 7 days Caution!
See cautions • May cause hemolytic
anemia, anophthalmia,
hypoplastic left heart
Page | 379
 syndrome, ASD, cleft lip
and palate;
• May be given on the 2nd
trimester of pregnancy
until 32 weeks age of
gestation only due to
above-cited risks;
• Use in the first trimester of
pregnancy is appropriate
only when NO OTHER
suitable alternative is
available.

Table 3.7. FDA Pregnancy Risk and Hale’s Lactation Risk Categories for
commonly prescribed antimicrobials in urinary tract infection.

Category Ba, L1, L2b Category Ca, L3b Category Da, 4, L3b

Co-amoxiclav 1 Cotrimoxazole 3 Aminoglycosides

Cephalosporins (avoid in 1st and
Nitrofurantoin 2 (must be 3rd trimesters)
used with caution; not
for near term)
ᵃRefer to the US FDA Pregnancy Risk Categories (See Appendix)
ᵇLactation Risk Category:
L1 – safest, controlled study = fails to demonstrate risk
L2 – safer, limited number of women studied without risk
L3 – moderately safe, no controlled study or controlled study shows
minimal, non-life-threatening situation
L4 – hazardous, positive evidence of risk, may be used if maternal life-
threatening situation
L5 – contraindicated, significant, and documented risk
1 Co-Amoxiclav: Avoid in those at risk for pre-term labor because of potential for neonatal
necrotizing enterocolitis
2 Nitrofurantoin: May cause hemolytic anemia, anophthalmia, hypoplastic left heart
syndrome, ASD, cleft lip and palate; may be given on the 2nd trimester of pregnancy until 32
weeks age of gestation only due to above-cited risks; use in the first trimester of pregnancy
is appropriate when NO OTHER suitable alternative is available.
3 Cotrimoxazole: Avoid especially during the first and third trimesters because of the risk for

teratogenicity and kernicterus.

4 Fluoroquinolones are likewise contraindicated in pregnancy

Page | 380
B. Acute Uncomplicated Cystitis in Pregnancy

1. When do you suspect acute uncomplicated cystitis in pregnancy?

a. In an otherwise healthy pregnant woman, acute cystitis is

characterized by urinary frequency and urgency, dysuria,
and bacteriuria without fever and costo-vertebral angle
tenderness. Gross hematuria may also be present.
b. Pathogens: E. coli (70%), other Enterobacteriaceae, Group
B Streptococcus

2. Is a pre-treatment diagnostic test required in acute cystitis in

pregnancy?

a. In pregnant women suspected to have acute

uncomplicated cystitis, obtain a pre-treatment urine culture
and sensitivity/ susceptibility test of a midstream clean-
catch urine specimen.
b. In the absence of a urine culture, the laboratory diagnosis
of acute cystitis is determined by the presence of significant
pyuria on urinalysis defined as a) >8 pus cells/mm3 of
uncentrifuged urine OR b) >5 pus cells/hpf of centrifuged
urine, AND c) a positive leukocyte esterase and nitrite test
on dipstick (Strong recommendation with moderate quality
of evidence).

3. What is the treatment for acute cystitis in pregnancy?

a. Treatment of acute cystitis in pregnancy should be

instituted immediately to prevent the spread of infection to
the kidney.
b. Since E. coli remains to be the most common organism
isolated, antibiotics to which this organism is most sensitive
and which are safe to give during pregnancy should be
used.
c. In the absence of urine culture and sensitivity, empiric
therapy should be based on local susceptibility patterns of
uropathogens.

Cotrimoxazole and fluoroquinolones are contraindicated

during pregnancy because of their potential teratogenicity
as well as the third-trimester risk of kernicterus with
cotrimoxazole.

Page | 381
 d. A 7-day treatment with an oral antibiotic that is safe for use
in pregnancy is recommended (see Table 3.8).

e. For a patient who is clinically responding to the present

treatment, there is no need to change the antibiotic that
was empirically started even if resistance is reported on
urine culture and sensitivity. Adjust antibiotic treatment
based on urine C/S only when there is no improvement in
the clinical signs and symptoms or laboratory results or
when there is worsening of the patient’s condition.

Table 3.8. Recommended antibiotics that can be used for acute cystitis in
pregnancy in the primary care facility.

ANTIBIOTICS RECOMME PREGNA BIRTH DEFECTS/ COMMENTS/

NDED NCY RISK COMPLICATIONS QUALIFIERS/
DOSE AND CATEGOR CAUTIONS
DURATION Y
Cefalexin 500 mg B None Safe in any
4x a day trimester
for 7 days
Cefuroxime 500 mg B None Safe in any
axetil 2x a day trimester
for 7 days
Nitrofuran- 100 mg B Hemolytic May be given only
toin 4x a day anemia, in the 2nd
macrocrys- for 7 days anophthalmia, trimester until 32
tals (for hypoplastic left weeks age of
Macrocry heart syndrome. gestation. Use in
stals) ASD, cleft lip the 1st trimester
and palate is
appropriate only
when NO OTHER
suitable
alternative is
available
.
Co- 625 mg B Neonatal Avoid in women
amoxiclav 2x a day necrotizing at risk of preterm
(Amoxicillin- for 7 days enterocolitis labor.
clavulanate)

Page | 382
 4. What is the clinical utility of a post-treatment urine culture?

a. Post-treatment urine culture 1 – 2 weeks after completion

of therapy should be obtained to confirm eradication of
bacteriuria and resolution of infection in pregnant women.
b. Pregnant patients with pyelonephritis, recurrent UTIs,
concurrent gestational DM, concurrent nephrolithiasis or
urolithiasis, and pre-eclampsia, should be monitored at
monthly intervals until delivery to ensure that urine remains
sterile during pregnancy.

C. Acute Uncomplicated Pyelonephritis in Pregnancy

1. When is acute uncomplicated pyelonephritis in a pregnant

woman suspected?

a. The classic syndrome of acute uncomplicated

pyelonephritis in healthy women also applies to pregnant
women. This is characterized by shaking chills, fever (T>38
°C), flank pain, nausea and vomiting, costovertebral angle
tenderness, with or without signs and symptoms of lower
urinary tract infections. Urinalysis shows pyuria of >5
WBC/hpf of centrifuged urine and bacteriuria of >10,000
CFU of a uropathogen/ mL on urine culture.
b. Common pathogens are similar to those causing acute
cystitis in pregnancy.

2. What is the recommended action for acute uncomplicated

pyelonephritis in pregnant women?

a. Pregnant patients with acute pyelonephritis should be given

immediate antimicrobial therapy and referred to a
specialist or a higher healthcare level facility.
b. Indications for admission are inability to maintain oral
hydration or take medications; concern about compliance;
the presence of possible complicating (co-morbid)
conditions; severe illness with high-grade fever, severe
pain, marked debility; signs of preterm labor; and signs of
sepsis (see Table 3.3).

3. To guide antibiotic choice and to establish an etiologic diagnosis,

what tests are done?

Page | 383
 a. Urinalysis with gram stain of uncentrifuged urine is
recommended to differentiate gram-positive from gram-
negative bacteriuria, which can guide the choice of empiric
antibiotic therapy.
b. Important Note: Urine culture and sensitivity/susceptibility
test should be done routinely to facilitate cost-effective use
of the antibiotic and to avert potential serious sequelae due
to an inappropriate antimicrobial.
Important Note: Blood cultures are not routinely
recommended unless sepsis is present.
c. Ultrasound of the kidney and urinary bladder are reserved
for failure to respond to antibiotic treatment.
4. What are the antibiotics that can be given for acute
pyelonephritis in pregnancy?

Table 3.9. Antibiotics that can be used for the treatment of acute pyelonephritis
in pregnancy in the primary care facility.
ANTIBIOTICS RECOMMENDED PREGNANCY BIRTH COMMENTS/
DOSE AND RISK DEFECTS/ QUALIFIERS/
DURATION CATEGORY COMPLICATI CAUTIONS
ONS
FIRST LINE (Oral)

Cefalexin 500 mg 4x a B None Safe in any

day for 14 days trimester

Cefuroxime 500 mg 2x a B None Safe in any

axetil day for 14 days trimester

Co-amoxiclav 625 mg 2x a B Neonatal Avoid in

(Amoxicillin- day for necrotizing women at
clavulanate) 14 days enterocoliti risk of
s preterm
labor.

5. What is the clinical utility of a post-treatment urine culture?

c. Post-treatment urine culture after completion of therapy

should be obtained to confirm the resolution of infection in
pregnant women.
d. Pregnant patients with pyelonephritis, recurrent UTIs,
concurrent gestational DM, concurrent nephrolithiasis, or
urolithiasis should be monitored with urine culture done at
Page | 384
 monthly intervals until delivery to ensure that urine remains
sterile during pregnancy

IV. Recurrent Urinary Tract Infection in Women

Summary of Recommendations
1. How is recurrent urinary tract infection (rUTI) in women diagnosed?

a. Recurrent UTI in women is diagnosed when a healthy, non-

pregnant woman with no known urinary tract abnormalities has 3
or more episodes of acute uncomplicated cystitis documented by
urine culture during a 12- month period, or, 2 or more episodes in
a 6-month period.
b. Recurrent UTI may either be a relapse or a re-infection.
• Relapse occurs when the initial organism persists
within the urinary tract and reemerges despite
adequate treatment usually occurring 1 – 2 weeks
after stopping treatment.
• Re-infection, on the other hand, occurs when the
recurrent UTI is caused by a different bacterial isolate,
or by the previously isolated bacteria after a negative
intervening culture or an adequate period (> 2 weeks)
between infections.

2. Among those with recurrent UTI, who would benefit from further
diagnostic evaluation?

a. Routine screening/ radiologic or imaging studies for urologic

abnormalities are not recommended for the general patient
population.
b. Screening for urologic abnormalities is recommended in the
following situations:
• No response to antimicrobial therapy or rapid relapse after
such therapy
• Gross hematuria during a UTI episode or persistent
microscopic hematuria
• Obstructive symptoms
• Clinical impression of persistent infection
• Infection with urea-splitting bacteria (Proteus, Morganella,
Providencia)
• History of acute pyelonephritis
• History of or symptoms suggestive of urolithiasis
Page | 385
 • History of childhood UTI
• Elevated serum creatinine.
c. Patients with the above factors may benefit from further
diagnostic evaluation as these risk factors have been identified to
be associated with a higher incidence of urologic abnormalities.
Referral to a higher level of healthcare or a specialist is
recommended.
d. All women with recurrent UTI should undergo a complete history
and physical examination to evaluate urogenital anatomy and
estrogenization of vaginal tissues and to detect prolapse. Post-
void residual urine should be measured. Referral to a gynecologist
is recommended.

3. What diagnostic work-ups are indicated in women with recurrent UTI?

a. Radiologic or imaging studies and cyctoscopy are not routinely

indicated in patients with recurrent UTI.
b. Renal ultrasound or CT scan/ stonogram may be done to screen
for urologic abnormalities.
c. Patients with anatomical abnormalities should be referred to a
specialist (nephrologist or urologist) for further evaluation.

4. When is prophylaxis for recurrent UTI indicated?

a. Prophylaxis is recommended in women whose frequency of

recurrence is not acceptable to the patient in terms of the level of
discomfort or interference of activities of daily living. Prophylaxis
may be withheld according to patient preference if the frequency
of recurrence is tolerable to the patient.
b. The following factors should guide the physician in determining
the patient’s risk-benefit profile and in deciding which prophylactic
strategies will be used:
• Frequency and pattern of recurrences
• Patient’s lifestyle, compliance, and willingness to commit to
the specific regimen
• Plans for a pregnancy
• Antimicrobial resistance and susceptibility pattern of the
organisms causing the patient’s previous UTIs
• Risks of adverse events and drug allergies.
c. Prophylaxis should only be initiated after counseling and behavior
modification have been attempted to minimize antibiotic exposure
and possible adverse effects.

Page | 386
 d. Antibiotic prophylaxis should be limited to women with recurrent
UTI in whom non-antimicrobial strategies have not been effective
and who prefer prophylactic antimicrobial therapy.

5. How effective are non-antimicrobial strategies in preventing recurrent

UTI?

a. Behavioral changes:
i. Behavioral changes can be useful in the prevention of
recurrent UTI. These include:
• Post-defecation and anal cleansing antero-
posteriorly always in women to avoid
contaminating the peri-urethral area with fecal
flora
• Post-coital douche or post-coital urination
• Liberal fluid intake especially after intercourse
• Avoidance of tight-fitting underwear
• Use of alternative forms of contraception for
women using spermicide-containing
contraceptives.

b. Biologic mediators:
i. Cranberry juice and cranberry products are not recommended
for the prevention of urinary tract infections in populations at
risk because there is no consistent evidence as to the
effective amount, concentration, and duration of intake.

c. Hormonal treatments in postmenopausal women:

i. Among postmenopausal women, the application of
intravaginal estriol cream or the use of estradiol releasing
silicone vaginal ring may be recommended for the prevention
of recurrent UTI. Referral to a gynecologist is recommended.
ii. Data is insufficient to recommend vaginal estrogens over
antibiotics for the prevention of recurrent UTI.
iii. Low-dose oral estrogen is not recommended for the
prevention of recurrent UTI.

d. Immunoprophylaxis: Referral to a gynecologist is recommended

for the possible use of immunoprophylaxis.

Page | 387
 6. How effective are antibiotic prophylactic regimens in preventing
recurrent UTI?

a. Prophylaxis with antibiotics is recommended in women whose

frequency of recurrence is not acceptable to the patient in terms
of level of discomfort or interference with activities of daily living.
Prophylaxis may be withheld if the frequency of recurrence is
tolerable to the patient.

b. If the decision to give antibiotic prophylaxis is made, any of the

following is recommended:
i. Continuous prophylaxis, defined as the daily intake of a low-
dose of antibiotics for 6-12 months (Strong
recommendation, moderate quality of evidence); or,
ii. Post-coital prophylaxis, defined as the intake of a single dose
of antibiotic immediately after sexual intercourse (Strong
recommendation, moderate quality of evidence); or,
iii. Intermittent prophylaxis, defined as self-treatment with a
single antibiotic dose based on the patient’s perceived need
(Strong recommendation, moderate quality of evidence).

c. Any of the antibiotics in Table 3.10, given either continuously for

6 to 12 months or as post-coital prophylaxis, can reduce the
clinical and microbiological recurrence of UTI episodes. (Strong
recommendation, moderate quality of evidence)

Page | 388
Table 3.10. Antibiotics that can be used for reducing the number of recurrences
of UTI in the primary care facility.

RECOMMENDED DOSES
ANTIBIOTICS Continuous Post-coital Intermittent
prophylaxis prophylaxis prophylaxis
Nitrofurantoin 50 to 100 mg at
bedtime for 6-12
months
Nitrofurantoin 50-100 mg
(as single
dose post-
coital)
Trimethoprim- 40/ 200 mg at
Sulfamethoxazole bedtime for 6-12
months
Trimethoprim- 40-80/ 200-
Sulfamethoxazole 400 mg (as
single dose
post-coital)
Trimethoprim- 320/ 1600 mg
Sulfamethoxazole for 1 dose at
symptom onset

7. How should individual episodes of UTI be treated in women with

recurrent UTI?

a. Any of the antibiotics for acute uncomplicated cystitis may be used

in the treatment of individual episodes of UTI in women with
recurrent UTI. (Strong recommendation, moderate quality of
evidence)

Page | 389
Table 3.11. Antibiotics for acute uncomplicated cystitis that may be used in the
treatment of recurrent UTI in women in the primary care facility.

ANTIBIOTICS Recommended Dose and

Duration
First Line Nitrofurantoin macrocrystals 100mg 4x a day for 5 days
per orem
Second Line Co-Amoxiclav (Amoxicillin- 625 mg 2x a day for 7 days
Clavulanate) per orem

Cefuroxime axetil 250 mg 2x a day for 7 days

per orem
To be used ONLY if Trimethoprim- 160/ 800 mg BID for 3 days
with proven sulfamethoxazole per orem
susceptibility (TMP-SMX)

b. Consider intermittent self-administered therapy in well-informed,

motivated, or educated patients, where the patients can recognize
the characteristic signs and symptoms of UTI, are compliant with
medical instructions, and have a good relationship with a medical
provider. (Strong recommendation, moderate quality of evidence)

c. Breakthrough infections during prophylaxis should be treated

empirically with any of the antibiotics recommended for
uncomplicated cystitis other than the antibiotic being given for
prophylaxis. Request for a urine culture and modify the treatment
accordingly. Refer to a higher level of healthcare facility or a
laboratory for the urine c/s.

8. How effective are non-pharmacologic interventions in treating UTIs?

a. Cranberry juice and cranberry products are not recommended for

the treatment of urinary tract infections.

b. There is evidence that acupuncture may prevent recurrent UTI

among women when antibiotic prophylaxis is contraindicated.

Page | 390
V. Complicated Urinary Tract Infections:
General Considerations

Summary of Recommendations
1. When is complicated urinary tract infection suspected or diagnosed?

Complicated urinary tract infection (cUTI) is significant bacteriuria plus

clinical symptoms which occurs in the setting of the following
conditions (see Table 3.12):
• Functional or anatomic abnormalities of the urinary tract
or the kidneys; or,
• The presence of an underlying disease that interferes with
the host defense mechanism; or,
• Any condition that increases the risk of acquiring
(persistent) infection and/or treatment failure.

The cut-off for significant bacteriuria in complicated UTI has been set
at 100,000 CFU/mL. However, in certain clinical situations, such as in
catheterized patients, low-level bacteriuria or counts < 100,000
CFU/mL may be significant.

The pathogens that cause complicated UTI are more varied and may
include drug-resistant organisms (e.g., ESBL-producing E. coli), P.
aeruginosa, and the enterococci.

Page | 391
 Table 3.12. Conditions that define complicated UTI
.
Presence of structural abnormalities causing urinary stasis and obstruction
of the genitourinary tract:
• Obstructive uropathy due to carcinoma, bladder outlet obstruction,
calculus, or cystocoele
• Urethral or ureteric strictures, tumors, calculi and other urologic
anatomic abnormalities
• Polycystic kidney disease
Functional abnormalities that affect normal urine outflow:
• Incomplete emptying of the bladder with > 100 mL retained urine
post-voiding
• Vesico-ureteral reflux
• Neurogenic bladder, spina bifida, multiple sclerosis
Conditions that interfere with host defense mechanisms:
• Azotemia due to intrinsic renal diseases
• Renal transplantation
• Diabetes mellitus
• Immunosuppressive conditions – e.g., febrile neutropenia,
myeloproliferative disorders, chemotherapy
Iatrogenic conditions:
• Presence of in-dwelling urinary catheter or intermittent
catheterization, stents
• Peri-operative or post-operative UTI
• Surgically created abnormalities
Pathogen-related complicating factors:
• UTI caused by unusual pathogens (M. tuberculosis, Candida spp)
• UTI caused by antibiotic-resistant or multi-drug resistant organisms
(MDRO)
Others:
• UTI in males except in young males presenting exclusively with
lower UTI symptoms
• Chemical or radiation injuries of the uroepthelium
• Urosepsis or severe pyelonephritis

2. What is the recommended management at the primary care facility?

It is best to refer the patient immediately to a specialist (nephrologist,

infectious disease consultant, or internist). However, the primary
physician may be called upon in the management, e.g., when the
outpatient parenteral antibiotic therapy (OPAT) will be the option.

Page | 392
 Before referral, a urine sample for gram stain, and culture and
sensitivity testing should be requested and may be done at a higher
level of healthcare facility or other laboratories. A urine G/S and C/S
should be done before the initiation of therapy. (Strong
recommendation, moderate quality of evidence)

The antibiotics that may be started for complicated UTI at the primary
care facility are listed below. It is important to do the following:
• always obtain urine for G/S, culture, and susceptibility tests
before the start of treatment;
• adjust the regimen as needed based on the culture and
susceptibility result;
• refer to a specialist; and,
• repeat urine culture 1 – 2 weeks post-treatment.

Table 3.13. Antibiotics that may be started for complicated UTI in adults in the
primary care facility.

ANTIBIOTICS DOSE AND RECOMMENDATIONS

DURATION
Oral * Ciprofloxacin 500 – 750 mg 2x a Adjust or switch
day for 7 – 14 days regimen based on
culture/ susceptibility
results

Co-amoxiclav 625 mg 3x a day, or, Adjust or switch

1 gram 2x a day regimen based on
for 7 – 14 days culture/ susceptibility
results

Parenteral * Amikacin 15 mg/ kg every 24 Adjust or switch

hours for 7 – 14 regimen based on
days culture/ susceptibility
results

Gentamicin 3-5 mg/kg every 24 Adjust or switch

hours for 7 – 14 regimen based on
days culture/ susceptibility
results

*For severely ill patients, start with parenteral broad-spectrum antibiotics the switch
to oral regimen or de-escalate when there is clinical improvement

Page | 393
VI. Urinary Tract Infections in Men

A. Uncomplicated Cystitis in Young Men

1. What is the definition of uncomplicated cystitis in young men?

• UTI in men is generally considered complicated.

• However, the first episode of symptomatic lower UTI in
young (15 – 40 years old) otherwise healthy sexually active
men with no clinical or historical evidence of a structural or
functional urologic abnormality are considered as
uncomplicated UTI.

2. How is uncomplicated cystitis in males diagnosed?

• Significant pyuria in men is defined as >10 WBC/mm3 or

>5 WBC/hpf in a clean catch midstream urine specimen.
This shows a good correlation with bladder bacteriuria and
the growth of >1,000 colonies of one predominant
species/mL of urine and best differentiates sterile from
infected bladder urine (Grade C).

3. What is the recommended diagnostic workup for uncomplicated

cystitis in men?

• Recommended diagnostic workup includes urinalysis and

urine culture.
• A pre-treatment urine culture should be performed routinely
in all men with UTI (Grade C).
• Routine urologic evaluation and use of imaging procedures
are not recommended (Grade C).

4. What is the recommended treatment?

• Seven-day antibiotic regimens are recommended (Grade

C).

• Antibiotics to be used depend on the prevailing

susceptibility patterns in the community or institution.
Refer to Section on Acute Uncomplicated Cystitis in Women
for antibiotic choices.

Page | 394
 Table 3.14. Categories reflecting the strength of evidence.

Grade Definition
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for
use
C Poor evidence to support a recommendation for or
against use
D Moderate evidence to support recommendation
against use
E Good evidence to support recommendation against
use

REFERENCES:
National Antibiotics Guidelines Committee. The National Antibiotics Guidelines
2019. Pharmaceutical Division, Department of Health, Philippine Blood
Center, DOH, QC.

The Task Force on Updates on the Diagnosis and Management of Urinary Tract
Infections in Adults. Philippine Clinical Practice Guidelines on the Diagnosis
and Management of Urinary Tract Infections in Adults: Asymptomatic
Bacteriuria, Recurrent Urinary Tract Infection, and Complicated Urinary
Tract Infection, 2015 Update (Part 2), PPGG-ID, Philippine Society for
Microbiology and Infectious Diseases, Quezon City, Philippines.

The Task Force on Updates in Urinary Tract Infection in Pregnancy, Philippine

Practice Guidelines Group in Infectious Diseases, 2013, Philippine Clinical
Practice Guidelines on the Diagnosis and Management of Urinary Tract
Infections in Adults: Urinary Tract Infections in Pregnancy 2013 Update,
PPGG-ID, Philippine Society for Microbiology and Infectious Diseases,
Quezon City, Philippines.

The Task Force on Urinary Tract Infections, Philippine Practice Guidelines Group
in Infectious Diseases, 2013, Philippine Clinical Practice Guidelines on the
Diagnosis and Management of Urinary Tract Infections in Adults:
Uncomplicated Urinary Tract Infection 2013 Update, PPGG-ID, Philippine
Society for Microbiology and Infectious Disease, Quezon City, Philippines.

Page | 395
The Task Force on Urinary Tract Infections 2003-04, Philippine Practice
Guidelines Group in Infectious Diseases, 2004, Philippine Clinical
Guidelines on the Diagnosis and Management of Urinary Tract Infections in
Adults 2004 Update, PPGG-ID, Philippine Society for Microbiology and
Infectious Diseases, Quezon City, Philippines, vol. 2, no. 1.

Page | 396
 Practice Essentials in the Diagnosis of Skin Lesions
and Interim Guidelines on the Management of
Common Cutaneous Bacterial Infections
in Adults at the Primary Care Level

Developed in collaboration with:

Dr. Camille B. Angeles, MD, FPDS
Dr. Mary Charmaine G. Castillo, MD, FPDS
Dr. Francisco D. Rivera IV, MD, FPDS
Dr. Ma. Purita D. Lao, MD, FPDS
Philippine Dermatological Society

I. What are the practice essentials in the diagnosis of skin

lesions?

A. HISTORY TAKING

The following information should be sought during the history taking:

1. Description of the lesions

• Description of the primary lesion including initial site or
location of the lesion/s, particularly its size, shape
and color;
• Description of the secondary lesions.
2. Evolution of lesions, taking into consideration the following:
• Manner of spread or progression of the lesions;
• Duration and, when applicable, evolution of lesions;
• In chronic eruptions, ask for periods of improvement or
resolution.
3. Associated signs and symptoms:
• Pruritus/ itchiness
• Pain, burning sensations
• Erythema, swelling
• Numbness

Page | 397
 • Factors that trigger (including time of day or any preceding
activity) or relieve the lesions or the associated signs and
symptoms
• Associated systemic symptoms, e.g., fever, joint pains,
and swelling, malaise
4. Topical and oral medications, including herbal
medications/supplements, used or taken from 12 weeks prior
to onset of skin lesions
5. Concurrent medical illnesses
6. Past medical illnesses
7. History of allergies and photosensitivity
8. Family history, e.g., history of psoriasis, skin cancer
9. Personal, social, sexual, and recent travel history

B. APPROACH TO CLINICAL EXAMINATION

1. Most of the cutaneous diseases are diagnosed based on the

gross clinical examination but a proper technique should be
followed.
2. Describe the cutaneous lesions, evaluating both the primary
skin lesions as well as the secondary skin lesions (see Table 4.3
and Table 4.4).
3. Examine the different areas of the skin as completely as
possible, taking note of the general condition of the skin and the
distribution of the lesions on initial evaluation.

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Table 4.1. History taking in dermatologic diagnosis.

HISTORY TAKING IN DERMATOLOGIC DIAGNOSIS

Chief Complaint and History of the Present Illness

• Duration: When was the condition first noted and dates of

recurrences or remissions
• Timing: Constant, intermittent, worst at night, worst during
summer
• Evolution: How the condition has changed or progressed over
time
• Location: Where lesions were first noted, and how they spread, if
applicable
• Symptoms: Pruritus, pain, bleeding, non-healing, change of pre-
existing lesions, associated with fever or other systemic
symptoms and signs
• Severity: Rate severity of pain or pruritus on a 10-point scale to
follow severity over time
• Ameliorating and Exacerbating Factors: Sun exposure, heat, cold,
trauma, exposures (such as to chemicals, medications,
cosmetics, [perfumes, plants, or metals), relation to menses or
pregnancy
• Preceding Illness, new medications, new topical products, or
exposures
• Therapies tried: Including non-prescription or home remedies,
and responses to therapy
• Prior Similar problems, diagnosis, results of biopsies, or other
studies performed

Medical History

• Chronic illnesses, particularly those that manifest in the skin (e.g.,

diabetes, renal and hepatic disease, HIV or other viral infection,
polycystic ovarian syndrome, lupus, thyroid disease) and those
associated with skin disease (asthma, allergy)
• Surgical procedures, including transplantation
• Immunosuppression: iatrogenic, infectious, or inherited
• Pregnancies
• Psychiatric disease

Page | 399
 • Photosensitivity, blistering sunburns
• Exposure to contactants or chemicals at home or the workplace
• Medication history: Detailed history including prescription and
nonprescription medications, vitamins, dietary supplements,
herbal remedies with particular attention to those started recently
• Allergies: to medications, food, environmental antigens,
contactants
• Family history: any skin diseases, atopy (atopic dermatitis,
asthma, hay fever), or skin cancer
• Social history: occupation, alcohol and tobacco use, illicit drug
use, diet, bathing habits, pets, living conditions (alone, with
family, in an institution, homeless), travel or residence in endemic
areas for infectious diseases, sexual history (including high-risk
activities for sexually transmitted diseases), cultural and religious
practices, hobbies, leisure activities
• Review of Systems: may be focused or more comprehensive
depending on the diagnosis (e.g., history of joint pains in
psoriasis)

Reference: Kang S, Amagal M, Bruckner AL, et.al. (eds). Fitzpatrick’s

Dermatology. Volume 1., 9th edition. 2019. McGraw Hill
Education, USA.

Page | 400
 Table 4.2. Physical examination in dermatologic diagnosis.

PHYSICAL EXAMINATION IN DERMATOLOGIC DIAGNOSIS

General impression of the patient

• Well or ill
• Obese, cachectic, or normal weight
• Skin color: degree of pigmentation, pallor (anemia), jaundice
• Skin temperature: warm, cool, or clammy
• Skin surface characteristics: xerosis (dryness), seborrhea (excessive
oiliness, turgor, hyper- or
hypohidrosis (excessive or decreased sweating), and texture
• Degree of photoaging: lentigines, actinic purpura., rhytides

Morphology

• Define the primary lesion

• Describe the color, texture
• Describe any secondary changes
• Describe shape and configuration
• Describe the distribution of lesions: localized (isolated), grouped,
regional, generalized, universal, symmetrical, sun-exposed, flexural,
extensor extremities, acral, intertriginous, dermatomal, follicular

Aspects of the Physical Examination that may be Helpful

• Vital signs
• Abdominal examination for hepatosplenomegaly
• Pulses
• Lymph node examination (especially in suspected infection and
malignancy)

Reference: Kang S, Amagal M, Bruckner AL, et.al. (eds). Fitzpatrick’s Dermatology.

Volume 1, 9th edition. 2019. McGraw Hill Education. USA.

Page | 401
Page | 402
Page | 403
Figure 1. Schematic representation of common skin lesions.

Reference: Longo, DL, Kasper, DL, Jameson, JL, et al. (eds.) Harrison’s Principles of
Internal Medicine, Vol.1, 2012.

C. DIAGNOSTIC TECHNIQUES:

When necessary, simple diagnostic procedures may be done at the

primary care clinic to provide more information. These include the
following:

1. Gram stain of the pus or exudates from skin lesions is

recommended to identify the etiologic agent but treatment
without performing this diagnostic test is reasonable in typical
cases.4

2. Potassium hydroxide (KOH) preparation:

a. Performed on scaly lesions where a fungal infection is

suspected (particularly to identify hyphae in
dermatophyte infections or pseudohyphae and budding

Page | 404
 yeast in Candida infections and “spaghetti and
meatballs” yeast forms in tinea versicolor);
b. Procedure:
i. scrape the edge of the lesion using a small
scalpel blade;
ii. place the collected scales on a clean glass slide;
iii. treat with 1 – 2 drops of 10 – 20% KOH solution
(KOH dissolves keratin to allow visualization of
the hyphae);
c. Under the light microscope, the refractile hyphae will be
seen.

3. Tzanck smear:

a. A cytologic test used to diagnose herpes simplex virus

(HSV) or varicella zoster virus (VZV)
b. The presence of multinucleated giant cells can confirm
that the lesion is herpetic but cannot differentiate
between HSV or VZV; (Note: culture or
immunofluorescence or genetic testing are necessary to
identify the specific virus)
c. Procedure:
i. unroof an early vesicle (do not choose a pustule
or crusted vesicle);
ii. scrape base of the lesion with a scalpel blade;
iii. place sample on a glass slide, air dry, and stain
with Giemsa or Wright’s stain.

4. Culture and sensitivity:

a. Cultures of the pus or exudates from skin lesions may be

performed to identify etiologic agents but treatment
without this is reasonable in typical cases.
b. Cultures of blood or aspirates, biopsies, or swabs are not
routinely recommended for classic cellulitis or erysipelas
but may be considered in patients with malignancy on
chemotherapy, neutropenia, severe cell-mediated
immunodeficiency, immersion injuries, and animal
bites.4

Page | 405
Figure 2. Schematic representation of the structure of the skin and soft tissues,
and depth of bacterial infections.

Reference: Rajan S. Skin and soft tissue infections: Classifying and treating a spectrum.
Cleveland Clinic Journal of Medicine. 2012:79(1):57-66. Available from:
https://www.mdedge.com/ccjm/article/95652/dermatology/skin-and-soft-tissue-
infections-classifying-and-treating-spectrum/page/0/1#).

II. What are the common cutaneous bacterial infections in

adults and their management?

SUPERFICIAL CUTANEOUS INFECTIONS AND PYODERMAS

A. IMPETIGO:

1. Etiologic Agents:

Page | 406
 Impetigo is a common superficial bacterial skin infection. This
is most often caused by Staphylococus aureus and in some
cases by group A β-hemolytic streptococci, or a combination
of both. The exfoliative toxin of S. aureus phage type II causes
the blister formation.

2. Clinical features;

a. Lesions appear on normal skin (primary infection), usually

on the face and exposed areas, or in areas already
affected by another skin disease (secondary infection).
b. Impetigo has two clinical forms: the non-bullous and the
bullous (less common) impetigo.
c. The primary lesion of non-bullous impetigo is an
erythematous papule that evolves into a vesicle and pustule
that rupture ruptures and expose a red, moist base covered
by a characteristic yellow-brown, honey-colored crust with a
“stuck-on” appearance.
d. Bullous impetigo presents with tense, clear vesicles and
bullae that easily rupture, creating crusted and
erythematous erosions.

Non-bullous Impetigo 1 Bullous impetigo 2

Erythematous plaques with honey- Erythematous plaques, vesicles,
colored crusts bullae, and erosions
Sources:
1 Bush, L. Staphylococal infections. MSD Manual. June 2019. Available from:

https://www.msdmanuals.com/professional/infectious-diseases/gram-positive-
cocci/staphylococcal-infections?query=impetigo. Accessed on: 21 Feb 2020
2 Cunfliffe T. Blistering (bullous) disorders. Primary Care Dermatology Society.

Available from: http://www.pcds.org.uk/clinical-guidance/bullous-disorders-an-

overview#!prettyPhoto. Accessed on: 21 Feb 2020.

Page | 407
 3. Prevention:

a. Observe proper hygiene.

b. Avoid sharing personal hygiene items.
c. Screen and treat all family members and close contacts
with impetigo.

4. Treatment:

a. For limited local infections:

• Mupirocin 2%, or, Fusidic acid 1% ointment or cream to

be applied 2 – 3 x a day for 7 -10 days.
• Gentle debridement of adherent crusts by cleansing
with soap or soap-free cleanser and water, facilitated by
soaking the lesions 3x a day in warm water or saline
solution to remove the crusts.

b. For widespread infections:

• Oral therapy is recommended for patients with

numerous lesions or in outbreaks affecting several
people to help decrease transmission of infection.
• Recurrent disease may be secondary to the
colonization of Staphylococcus aureus in the nares.
Mupirocin cream or ointment may be applied 2 x a day
to the anterior nares for 5-10 days.
• A penicillinase-resistant systemic antibiotic such as the
following may be used:
- Cloxacillin 250 mg; or,
- Cefalexin 250 mg 4 x a day; or,
- Sodium fusidate 250 – 500 mg 2 to 3x a
day may be prescribed.

Page | 408
 Table 4.5. Alternative antibiotics for impetigo in adults.

Organisms Drug of Choice Alternative

Group A Streptococcus Erythromycin
Cefalexin

Grp A Strep & S. aureus Clarithromycin

Azithromycin

MRSA Minocycline Cotrimoxazole

(Methicillin Resistant Sodium fusidate 250 Ciprofloxacin
Staphylococcus aureus – 500 mg/ tab 2x or
3x a day for 7- 14
days

Reference: Philippine Dermatological Society. Treatment Guidelines on

Common Primary Bacterial Infections. PPD’s Compendium of Philippine
Medicine. 11th ed. 2009.

B. ECTHYMA:

1. Etiologic agent:
Ecthyma is caused by S. aureus and/or Group A Streptococcus
and classically evolves from untreated impetigo, and extends
more deeply, penetrating the epidermis.
2. Clinical features:
a. Ecthyma occurs most commonly on the lower extremities
of children and neglected elderly patients.
b. Punched-out, saucer-shaped ulcers with a raw base and
elevated edges.
c. Ulcer margins are indurated, raised, and violaceous, with
typical surrounding edema.
d. Grayish-yellow crusts may be appreciated, as well as
purulent material on the surface of the lesion.
3. Treatment:
a. Cleansing with soap and water, followed by application of
mupirocin, bacitracin, or fusidic acid cream or ointment 2
– 3 x a day.
b. Cloxacillin, or, a first-generation cephalosporin must be
given systemically.

Page | 409
Ecthyma. Punched-out ulcers with grayish-blackish crusts, erythematous base.
Source: Miller, L. Chapter 150. Superficial Cutaneous Infections and Pyodermas.
In: Kang S, Amagal M, Bruckner AL, et.al. (eds). Fitzpatrick’s
Dermatology. Volume 1, 9th edition. 2019. McGraw Hill Education.
USA.

C. FOLLICULITIS:

1. Etiologic agent: A pyoderma of the superficial portion of the hair

follicle caused by S. aureus.

2. Clinical features:
a. Found on hair-bearing areas: scalp, beard, axilla, buttocks,
and legs.
b. Primary lesion is a pustule located at the infundibulum
(ostium or opening) of a hair follicle.
c. Tenderness may be present.

3. Treatment:
a. Antibacterial soap and topical antibiotics like mupirocin or
fusidic acid are effective in limited areas of involvement.
b. Oral anti-Staphylococcal antibiotics (oxacillin, cloxacillin,
cefuroxime, sodium fusidate) are indicated for extensive
cases.

Page | 410
 c. Heat, friction and occlusion should be avoided or
minimized.

Figure 4. Schematic diagram of bacterial infections of the hair follicle.

References: https://www.mayoclinic.org/diseases-conditions/folliculitis/symptoms-
causes/syc- 20361634 https://www.webmd.com/skin-problems-and-
treatments/ss/slideshow-boils

Folliculitis Furuncle Carbuncle

Source: Miller, L. Chapter 150. Superficial Cutaneous Infections and Pyodermas. In: Kang
S, Amagal M, Bruckner AL, et.al. (eds). Fitzpatrick’s Dermatology. Volume 1, 9th edition.
2019. McGraw Hill Education. USA.

D. FURUNCLE (FURUNCULOSIS) AND CARBUNCLE:

1. Etiologic agent:
Furunculosis (boil) often evolves from S. aureus folliculitis but
can be caused by Methicillin-sensitive (MSSA) or Methicillin-
resistant (MRSA). This has become important due to the
emergence of Community-acquired – MRSA.
Page | 411
 2. Clinical Features:

a. A furuncle, or boil, is a walled-off, deep, hard, tender,

erythematous nodule that develops around a hair follicle,
usually from a preceding folliculitis. It then enlarges and
becomes painful and fluctuant after several days. It will
then rupture with the discharge of pus. The lesions may be
solitary or multiple. Furuncles usually arise in hair-bearing
areas, particularly in those subjected to friction, occlusion,
and perspiration, e.g., face, neck, axilla, buttocks. Family
and close contacts may also be affected.

b. A carbuncle is a more extensive, deeper, communicating,

infiltrated, extremely painful lesion that develops when
multiple, closely set furuncles coalesce or become
interconnected. it clinically presents as an erythematous
indurated area, with multiple pustules on the surface. Areas
of predilection include the neck, back, and thighs. Fever
and malaise are often present.

3. Treatment:

a. Warm, moist compresses are applied for 15 – 30 minutes

several times a day.

b. Incision and drainage:

Incision and drainage remain as the primary management
for fluctuant lesions. Furuncles can rupture and drain
spontaneously or need incision and drainage which may
already be adequate for small solitary furuncles without
cellulitis or systemic symptoms.

Needle aspiration is inadequate.

Whenever possible, samples of the lesions should be sent

for culture and sensitivity.

c. Antimicrobial Therapy (National Antibiotic Guidelines,

2019):

i. Outpatient management: for patient without diabetes

or immunosuppression, with boil or smaller abscess
(<2 cm in diameter):

Page | 412
 o Incision and drainage only are usually effective;
o Hot packs are helpful;
o No need for antimicrobial therapy.

ii. Outpatient management: for larger lesions (>2 cm in

diameter within an area of erythema of >5 cm) or
multiple abscesses, or patient with systemic
inflammatory response syndrome (SIRS):
o Incision and drainage PLUS
o Clindamycin 300 – 450 mg (higher dose in obese
patient, with BMI >40) per orem 3x a day for 5 – 10
days; or,
o Cotrimoxazole 160/800 mg (1 tablet of 160/800
mg tablet or 2 tablets of 160/800 mg tablet in
obese patients, with BMI >40); or,
o Doxycycline 100 mg per orem every 12 hours for 5
– 10 days (may also be effective for community-
acquired MRSA infections).

iii. If no response after 2 – 3 days:

o Follow-up exudate culture and sensitivity results if
these were done and refer to facility with higher
level of care;
o Or, if C/S results are not yet available, may shift to
another First Line antibiotic.

i. Additional information (National Antibiotic Guidelines,

2019):
o For documented Methicillin-sensitive
Staphylococcal aureus (MSSA), a beta-lactam is
the preferred agent:
o Cloxacillin 500 mg per orem 4x a day; or,
o Cephalexin 500 mg per orem 3x – 4x a
day

o For documented Methicillin-resistant

Staphylococcal aureus (MRSA) infections, Linezolid
IV (refer to a higher level of health facility).

ii. Recurrent furunculosis (National Antibiotics

Guidelines, 2019):

o Treat as for furuncles and boils.

Page | 413
 o Decolonization may be attempted to eradicate
the nasal carriage of Staphylococus aureus with
the use of Mupirocin ointment to be applied in
the anterior nares and under the fingernails 2x a
day for 5 – 7 days PLUS Chlorhexidine 4%
shower daily for 5 – 7 days.
o Clinical setting for decolonization does not apply
to persons who inject drugs. If the patient wishes
to attempt decolonization, the patient should
have no active skin infections and is otherwise
healthy. Need to culture multiple sites, e.g., nose,
throat, and skin. Nares only cultures missed 48%
of colonized individuals.

E. CELLULITIS and ERYSIPELAS:

1. CELLULITIS

a. Etiologic agent:
i. Most common cause is Group A Streptococci (Strep.
pyogenes) and Staphylococcus aureus.
ii. It is an infection of the deep dermis and subcutaneous
tissue.

b. Clinical Features:
i. The bacteria gain access through breaks in the skin,
through abrasions, cuts, burns, insect bites, surgical
incisions, and IV catheters, where they can spread into
lymphatics, blood vessels, and interstitial spaces.
ii. Disseminated infection with secondary seeding of the
skin is a rare cause that may occur in
immunocompromised patients.
iii. Unilateral lower extremity involvement is typical, and
systemic symptoms are usually absent.
iv. A spreading, ill-defined erythematous, edematous
macule or patch, that is often warm, tender, or painful.
v. Sometimes with small areas of spared intervening skin,
so-called “skip areas”.
vi. May be associated with lymphangitis or tender regional
lymphadenopathy.

Page | 414
 c. Treatment:
i. Warm compresses and analgesics to relieve pain.
ii. Elevation of an involved limb hastens recovery.
iii. Empiric treatment with antibiotics aimed at
Staphylococcal and Streptococcal organisms is
appropriate
iv. Refer to higher level of health facility if with the
following indications for parenteral administration of
antibiotics:
o Failed outpatient treatment
o Presence of at least two of the following signs of
Systemic Inflammatory Response Syndrome
(SIRS):
 temperature: > 380 C or < 36 0C
 pulse rate: > 90 beats/min
 respiratory rate: > 20 breaths/min
 leukocyte count >12,000 cells/µL or <
4,000 cells/ µL
o Associated with penetrating trauma
o MRSA infection elsewhere
o Nasal colonization with MRSA
o Injection drug use

Cellulitis Erysipelas
Poorly defined warm, tender erythema. Well defined, bright red
edema.
Source: Pearson DR, Margolis DJ. Chapter 51. Cellulitis and Erysipelas In: In: Kang S, et
al., eds. Fitzpatrick’s Dermatology. 9th edition. 2019.

2. ERYSIPELAS

a. Etiologic agent:

Page | 415
 i. Most common cause is Group A Streptococci (Strep.
pyogenes) and Staphylococcus aureus
ii. Recent studies and literature consider erysipelas a
clinical variant of cellulitis that predominantly affects
the superficial lymphatic vessels

b. Clinical Features:

i. An acute inflammatory condition of the skin with

prominent lymphatic involvement
ii. Characterized by an acute onset of intense redness
and swelling
iii. Lesions are sharply demarcated and bright red
iv. Flaccid bullae may develop during the 2nd and 3rd days
v. Extension to deeper tissues is rare
vi. Most commonly located on the leg, followed by the
face and upper limbs
vii. Prodromal symptoms consist of malaise, chills, fever,
and occasionally, anorexia and vomiting

c. Treatment:

i. Same as non-pharmacologic treatment for cellulitis,

plus:
ii. Penicillin V orally (250 – 500 mg 4x a day) is the drug
of choice.
iii. Erythromycin can also be used.
iv. Alternatives for patients who cannot take penicillins:
o Azithromycin 500 mg on Day 1 and 250 mg on days
2 – 5; or,
o Clarithromycin 250 to 500 mg every 12 hours for 7
– 14 days.

3. SPECIAL CONDITIONS

a. Erysipelas and Diabetes Mellitus:

i. Patients with diabetic peripheral neuropathy commonly

suffer from inflammation of the skin and subcutaneous
tissues. The patients may develop contiguous skin
ulceration and/or atherosclerotic peripheral vascular
disease

Page | 416
 ii. Etiologic agents: Streptococcus sp., (Group A, B, C, G),
S. aureus, Enterobacteriaceae, Anaerobes (poor
prognosis if present)

iii. Antibiotic Therapy for Erysipelas in Patients with DM:

(National Antibiotics Guidelines, 2019):

First Line Outpatient Therapy for early or mild infection:

o Clindamycin 300 – 450 mg (higher dose in

obese patient, BMI >40) per orem 3 x a day for
5 – 10 days; or,
o Cotrimoxazole 160/800 mg 1 – 2 tablets per
orem 2 x a day; PLUS Penicillin VK 500 mg per
orem 4x a day; or,
o Cephalexin 500 mg per orem 4x a day.

iv. It is important to assess the adequacy of the arterial

supply.

b. Acute Bacterial Skin and Skin Structure Infections (ABSSSI):

i. This section focuses on the treatment of uncomplicated

cellulitis, erysipelas in extremities, and other ABSSSI in
the Non-Diabetic patient.

ii. Etiologic agent: S. pyogenenes (Group A, B, C, G), S.

aureus (rare)

iii. Clinical features:

o Acute onset of rapidly spreading red,
edematous, tender plaque-like area of the
skin, usually in the lower leg, often with fever.
It may be associated with lymphangitis or
lymphadenitis.
o The facial skin may also be involved
o The portal of entry is often through a fungal
infection between the toes (tinea pedis)

iv. Bedside ultrasound may help in detecting deep S.

aureus abscess. If in doubt, treat for both. Community-
Acquired MRSA may mimic erysipelas. Look for
loculated purulence.

Page | 417
 v. Antibiotic Therapy of ABSSI: (National Antibiotics
Guidelines, 2019):

1) For S. pyogenes (Groups A, B, C, G) infection:

First Line Outpatient Therapy for less ill patients:

a) Antibiotics to be given are either:

- Penicillin VK 500 mg per orem 4x a day;
or,
- Amoxicillin 500 mg per orem every 8
hours.

b) If with history of skin rash to penicillin

and no Ig-E mediated reaction
(anaphylaxis and angioneurotic edema),
give:
o Cephalexin 500 mg per orem 2x a day
for 10 days.

c) If with a documented past history of Ig-E

mediated allergic reaction to beta-
lactam antibiotics, give:
- Azithromycin 500 mg per orem for 1
dose, then 250 mg per orem daily
for 4 days; or,
- Linezolid 600 mg per orem 2x a day for
10 days.

d) If clinically unclear whether infection is

due to S. pyogenes or S. aureus, get
cultures and start empiric therapy as
follows:
For S. pyogenes:
- Amoxicillin; or,
- Penicillin VK; or,
- Cephalexin.
For S. aureus (MRSA):
- Clindamycin.

e) For suspected S. aureus (with fluctuance

or positive Gram stain):

Page | 418
 For MSSA (as outpatient):
- Cloxacillin 500 mg PO QID;
For MRSA (as outpatient):
-Doxycycline 100mg PO BID, or,
Clindamycin 300-450 mg PO BID.

* If S. aureus is present, there is a need for incision and drainage.

Antimicrobial Resistance ALERT and Precautions:

 Do not use Fluoroquinolone, Cotrimoxazole, or a
Tetracycline for reasons of resistance and/ or clinical
failures to these antibiotics.
 Stasis dermatitis due to venous insufficiency can
masquerade as bacterial cellulitis/ erysipelas; the
condition is often bilateral, chronic, and has no febrile
states.
 Systemic antibiotics do not offer additional benefits in
these cases.

2) For S. aureus (predominantly MRSA, also

MSSA) and rarely, beta-hemolytic Streptococci:

First Line Therapy for non-severely ill patients:

o Clindamycin, 300 – 450 mg (higher dose

in obese patient BMI >40) per orem 3x a
day for 5 – 10 days; or,

o Cotrimoxazole 160/800 (1 DS tablet, 2 DS

tablets in obese patient BMI > 40) per
orem BID for 5 – 10 days; or,

o Doxycycline 100 mg per orem every 12

hours for 5 – 10 days may also be effective
for CA-MRSA.

o For documented MSSA infection: use a

beta-lactam agent:

Page | 419
 Oral: Cloxacillin 500 mg per orem 4x a day;
or, Cephalexin 500 mg per orem 3x or 4x a
day.

* Culture of blood, exudate, and/or bullae is needed when there are

signs of systemic toxicity, extensive skin involvement, or underlying
co-morbidities. Refer the patient immediately to a higher level of
health facility.

REFERENCES:
1 Longo, DL, Kasper, DL, Jameson, JL, et.al (eds.) Harrison’s Principles of Internal
Medicine, Volume 1, 18th Edition. 2013. Mc-GraHill Company, USA.
2 National Antibiotics Guidelines Committee. National Antibiotic Guidelines 2019.
2018, Department of Health, Philippine Blood Center, QC.
3 Philippine Dermatological Society. Treatment Guidelines on Common Primary
Cutaneous Bacterial Infections. 2009. PPD’s Compendium of
Philippine Medicine. 11th ed.
4 Miller L. Superficial cutaneous infections and pyodermas. In: Krager S, Amagai
M, Bruckner AL, et. al. (eds). Fitzpatrick’s Dermatology Volume 1, 9th
edition. 2019. McGraw Hill Education, USA.
5 Pearson DR, Margolis D. Cellulitis and Erysipelas. In: Krager S, Amagai M,
Bruckner AL, et. al. (eds). Fitzpatrick’s Dermatology Volume 1, 9th
edition. 2019. McGraw Hill Education, USA.
6 James, W, Berger, T, Elston D, Andrew’s Diseases of the Skin: Clinical
Dermatology. 11th edition. 2011. Saunders Elservier, USA.
7 Stevens, D, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis
and Management of Skin and Soft Tissue Infections: 2014 Update by
the Infectious Diseases Society of America. Clin Infect Dis.
2015:59(2):e10-52. Available at:
https://www.idsociety.org/globalassets/idsa/practice-
guidelines/practice-guidelines-for-the-diagnosis-and-management-of-
skin-and-soft-tissue-infections-2014-update-by-the-infectious-
diseases-society-of-america.pdf. Accessed on: January 8, 2020.

Page | 420
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Page | 422
Page | 423
Page | 424
Page | 425
Page | 426
REFERENCES:
Bravo LC, Gatchalian SR, Gonzales MLM, et. al. Handbook of Pediatric Infectious
Disease, 5th Edition. UP College of Medicine-Philippine General Hospital;
2011.
Department of Child and Adolescent Health and Development. Handbook IMCI
Integrated Management of Childhood Illness. World Health Organization
and UNICEF. Geneva; 2005.
Department of Child and Adolescent Health and Development. The Treatment of
Diarrhea: A Manual for Physicians and other Senior Health Workers. World
Health Organization. Geneva; 2005.

Page | 427
 Interim Guidelines on the Antibiotic Treatment of
Infectious Diarrhea at the Primary Care Level

Based on the Philippine 2019 National Antibiotics Guidelines

I. What are the guidelines in the management of

infectious diarrhea in infants and children?
The mainstay of treatment of acute diarrhea is adequate hydration,
proper food, and zinc supplements (refer to Algorithm on Diarrhea and
Dehydration).

When an infectious etiology is suspected or confirmed, the following

are the recommended guidelines in the choice of antibiotics.

A. Etiology by Age:

1. Less than 12 months of age: Rotavirus, Enterotoxigenic

Escherichia coli (ETEC), Cryptosporidium
2. 12 – 23 months of age: Rotavirus, ETEC, Shigella
3. 24 – 59 months old: Rotavirus, Shigella, Vibrio cholera

B. Antibiotic Regimen (refer to the National Antibiotics Guidelines

2019 for full details):

1. Suspected dysentery:
a. Ciprofloxacin:
i. 0 – 2 months old: 30 mg/kg/day per orem in 2
divided doses x 3 days
ii. 2 months to 5 years old: 30 mg/kg/day in 2
divided doses x 3 days
NOTE: For children with severe dehydration living in an
area with reported cases of cholera, give antibiotics for
cholera.
For acute diarrhea with dysentery (blood in the stool),
give ciprofloxacin for 3 days.
For suspected antibiotic-associated colitis, mild disease
does not warrant antibiotic treatment since symptoms
resolve within 7-10 days after discontinuing precipitating
antibiotics.
2. Suspected cholera:
a. Erythromycin: 250 mg per orem 4x a day x 3 days; or,

Page | 428
 b. Tetracycline: 250 mg per orem 4x a day x 3 days.
3. Campylobacter:
a. Azithromycin: 10 mg/kg/day per orem x 3 days; or,
b. Erythromycin 40 mg/kg per prem in 4 divided doses
per day x 5 days.
4. Entamoeba histolytica:
5. Metronidazole: 35 – 50 mg/kg per orem in 3 divided doses
per day x 7 - 10 daysGiardia:
a. Metronidazole: 15 mg/kg per orem divided into 3
doses per day for 5 – 7 days
6. Cyclospora:
a. Co-Trimoxazole: 10 mg TMP/ 50 mg SMX/ kg per
orem in 2 divided doses per day x 7 – 10 days.

II. What are the guidelines in the management of

gastroenteritis (infectious diarrhea) in adults?

A. Bacterial Gastroenteritis:

1. Etiologic organisms:
a. Shigella sp.
b. Salmonella sp.
c. C. jejuni
d. C. difficile (Toxin positive)
e. E. coli (enterotoxigenic, enteroaggregative, Shiga-
toxin producing)
f. K. oxytoca (Toxin producer)

2. Empiric treatment:
a. Ciprofloxacin 500 mg per orem every 12 hours for 3 –
5 days; or,
b. Levofloxacin 500 mg per orem every 24 hours for 3 –
5 days; or,
c. Azithromycin 500 mg per orem every 24 hours for 3
days (preferred for Campylobacter); or,
d. Co-trimoxazole 160/800 mg per orem 2x a day for 3
– 5 days.

3. Specific Therapy:
a. For Shigella species:
i. Co-trimoxazole 160/800 mg per orem 2x a day
for 3 days; or,

Page | 429
 ii. Ciprofloxacin 500 mg per orem 2x a day for 3
days.

B. Parasitic Gastroenteritis:
1. Etiologic organisms:
a. Giardia lamblia
b. Entamoeba histolytica
c. Cryptosporidium
2. Specific therapy:
a. For Entamoeba histolytica:
i. Metronidazole 500 – 750 mg per orem 3x a day
for 7 – 10 days; or,
ii. Tinidazole 2 grams per orem per day for 3 days.

C. For Vibrio cholera:

1. Specific therapy:
a. Doxycycline 300 mg for 1 dose; or,
b. Tetracycline 500 mg 4x a day for 3 days; or,
c. Co-trimoxazole 160/800 per orem 2x a day for 3 days.

Page | 430
Page | 431
Page | 432
Page | 433
 Updated Interim Guidelines on the Management of
Hypertension in Adults at the Primary Care Level

Developed in collaboration with:

Dr. Ronald Cuyco, FPCP, FPHA

Dr. Ryan Buendia, FPCP, FPHA
Dr. Nanette Rey, FPCP, FPHA
Philippine Heart Association

Dr. Albert Atilano, FPCP, FPHA, FPSH

Philippine Society of Hypertension

I. What is the definition of hypertension (HTN)?

A. Definition of Hypertension and BP Categories

The Philippine Heart Association and the Philippine Society of

Hypertension (PHA / PSH) in a joint statement issued in 2017 which
was based on the results of the consensus meeting with the
representatives from the Public Health and Clinical Epidemiology
sector, the Philippine Society of Nephrology and the Philippine
Neurological Association, have defined hypertension as follows: 3

1. Hypertension is defined as an office (or clinic) BP of

140/90 and above. It is reasonable to consider a
Home BP Monitoring (HBPM) of 135/85 and above
as hypertensive level.
2. Borderline BP is defined as a BP of 120–139/ 80–
89.
3. Normal BP is defined as a BP of less than 120/80.

Page | 434
Table 6.1. BP categories in adults.

BP CATEGORY SBP DBP

Normal < 120 mm Hg and < 80 mm Hg

Borderline 130–139 mm Hg and 85-89 mm Hg

Hypertension

Stage 1 140–159 mm Hg or 90–99 mm Hg

Stage 2 > 160 mm Hg or > 100 mm Hg

Hypertension is diagnosed if the BP levels of 140/90 or above are

noted during measurements taken in at least 2 visits at least 1 week
apart or during the first visit with the patient exhibiting evidence of
target organ damage (e.g., cardiac, renal, cerebrovascular, peripheral
vascular, or ophthalmologic). BP is measured with the patients
seated.

It is important to note that the initiation of pharmacologic treatment

will depend on the presence of factors other than the BP
measurements (please refer to Section III – B).

B. Method for Indirect Measurement of Blood Pressure

1. The digital BP apparatus is the preferred instrument for BP

measurement both during diagnosis and monitoring. When this
is unavailable, at the primary care facility, an aneroid BP
apparatus is acceptable. The aneroid BP device may also be
used when there is an extremely high BP (e.g., systolic BP > 200
mm Hg) or in the presence of irregular heart or pulse beats.

2. Aneroid, digital, or other automated devices must satisfy

technical requirements for accuracy and be calibrated and
tested regularly.

3. The manometer cuff should cover at least 2/3 of the length of

the patient’s arm while the bladder should cover at least 80% of
the arm circumference.

Page | 435
 4. The patient should be seated or supine with arms bared,
supported, and at heart level. He should have rested for at least
5 minutes, and should not have smoked or ingested caffeine
within 30 minutes before measurement.

5. The edge of the cuff should be placed 1 inch above the elbow
crease with the bladder directly over the brachial artery.

6. When taking the BP using the aneroid device, the following

techniques should be done:
a. The bladder should be inflated to 30 mmHg above the point
of radial pulse extinction as determined by a preliminary
palpatory determination. It should then be deflated at a rate
of 2 mmHg/beat with the stethoscope bell placed directly
over the brachial artery.

b. The systolic pressure should be recorded at the

appearance of the 1st clear tapping sound (Korotkoff
phase 1).
c. Diastolic BP should be recorded at the disappearance of
these sounds (Korotkoff phase V) unless these are still
present near 0 mmHg in which case the softening of the
sounds shall be used as diastolic pressure (Korotkoff phase
IV).

7. For every visit, the mean of 2 readings, taken at least 2 minutes

apart, should be regarded as the patient’s BP. If the first 2
readings differ by 5 mmHg or more, a 3rd reading should be
included in the average.

8. If BP is being taken for the 1st time, the procedure should be

repeated on the other arm. Subsequent determinations should
then be performed on the arm with a higher blood pressure
reading.

9. All members of the healthcare facility must be trained to do proper

BP measurements. However, it is strongly advised that only one
particular staff member will be assigned to measure the BP
measurement during all consultations.

Page | 436
 C. Home and Ambulatory BP Monitoring

Out-of-office or self-BP monitoring using either Home BP Monitoring

(HBPM) and Ambulatory BP Monitoring (ABPM), when logically or
economically feasible in the primary healthcare setting, is an
important measure in the accurate diagnosis of clinical hypertension,
in the detection of white-coat and masked hypertension, and in
monitoring BP control.

The use of the digital BP apparatus during HBPM is recommended for

the diagnosis of true hypertension and monitoring treatment
response. This was validated as giving the closest approximation of
the 24-hour ambulatory BP measurement. Recommendation for ABPM
is usually made by the hypertension specialist when such monitoring
becomes necessary.

D. Conditions where HTN is Suspected

1. Whitecoat HTN defined as BP elevation in the clinic setting but

which is repeatedly normal out of the office.

2. Isolated systolic HTN defined as systolic BP of 140 mmHg or

more and a diastolic BP of less than 90 mmHg.

3. Masked HTN defined as a condition where the patient’s office or

clinic BP is <140/90 mm Hg but ambulatory or home BP
readings are in the hypertensive range.

II. What is the approach to the diagnosis of a patient with

HTN?

A. Objectives of Evaluation

1. To assess lifestyle and identify other cardiovascular risk factors

and concomitant disorders that can affect prognosis and
treatment

2. To reveal identifiable causes of hypertension

3. To assess the presence or absence of target organ damage and

cardiovascular diseases.

Page | 437
 B. Risk Factors for Cardiovascular Disease

The PHA-PSH recommends the use of traditional risk factor counting

over the use of the Atherosclerotic Cardiovascular Risk Scoring
(ASCVD) calculator in the identification of the risk factors in the
patient. 3

Table 6.2. Risk factors for cardiovascular disease.

Modifiable Risk Factors Non-Modifiable Risk Factors

Smoking Age (Older than 55 years for men, 65

years for women)
Hypertension
Male gender
Dyslipidemia
Family history of premature
Diabetes Mellitus cardiovascular disease (men <55 years
of age, or women <65 years of age)
Obesity (BMI >30 kg/m2)

Physical Inactivity

Estimated GFR <60 mL/min

Microalbuminuria

C. Information Included in Medical History

1. Duration of HTN and previous level of BP

2. Secondary Hypertension:

a. Family history of chronic kidney disease or Polycystic Kidney

Disease
b. History of renal disease, UTI, hematuria, and analgesic
abuse
c. Drug/substance intake: NSAIDs, steroids, amphetamine
vasoconstrictive nasal drops, oral contraceptives, and
cocaine
d. Repetitive sweating, and palpitations (pheochromocytoma),
headaches, and anxiety
e. Tetany (hyperaldosteronism) and episodic muscle
weakness
f. Thyroid disease

Page | 438
 3. Risk Factors that Include:

a. Family and personal history of HTN and cardiovascular

disease, dyslipidemia, and diabetes
b. Smoking habits
c. Dietary habits
d. Weight changes, obesity
e. Physical exercise
f. Snoring, sleep apnea
g. Low birth weight

4. History and symptoms of organ damage and cardiovascular

diseases:

a. Brain and eyes: headache, vertigo, TIA, blurring of vision,

and stroke
b. Heart: chest pains, shortness of breath, ankle edema, MI,
syncope, and palpitations
c. Kidney: thirst, polyuria, nocturia, and hematuria
d. Snoring or chronic lung disease
e. Peripheral arteries: cold extremities, intermittent
claudication

5. HTN management:

a. Current medicines
b. Past medicines
c. Compliance
d. Efficacy and adverse effects of the medicines
e. Concurrent medications, herbal medicines, and
supplements that may affect BP or response to treatment

6. Substance abuse, and physical, psychosocial, domestic, and

occupational stresses.

D. Information included in Physical Examination

1. Appropriate measurement of BP;

2. Height and weight measurement, waist-hip ratio, and calculation

of Body Mass Index (BMI) computed as:

BMI = [ (Weight / 2.205) / (Height / 39.37)² ] in kg/m²

3. Head and Neck: carotid bruits, distended veins, and thyroid

enlargement;

Page | 439
 4. Chest and Lungs: heart rate, point of maximal impulse, apex
beat, heaves, clicks, murmurs, arrhythmias, gallops, and
examination of the lungs;

5. Abdomen: examination for truncal obesity, purple striae, bruits,

enlarged kidneys, masses, and abnormal aortic pulsations;

6. Extremities: diminished or absent peripheral arterial pulsations,

bruits and edema, arm BP discrepancies >10 mmHg or when
indicated similar discrepancies between leg BPs, postural
hypotension in the elderly (>10 mmHg drop on assumption of
upright from recumbent position);

7. Neurologic assessment for stroke residuals or encephalopathy.

E. Laboratory Tests

1. Routine laboratory tests: urinalysis, serum potassium, fasting

blood glucose, and creatinine;

2. Special tests are indicated if BP remains poorly controlled or if

the history, PE, and routine laboratory tests indicate other organ
involvement. These tests include ECG, chest X-ray, lipid profile,
uric acid, hematocrit, and test for microalbuminuria.

3. Confirmatory tests for secondary HTN will be requested by the

HTN specialist. Clinical clues will suggest the identifiable cause
(e.g., chronic kidney disease, coarctation of the aorta, Cushing’s
syndrome, and other glucocorticoid excess states including
chronic steroid use, drug-induced, obstructive uropathy,
pheochromocytoma, primary aldosteronism, and other
mineralocorticoid excess states, renovascular HTN, sleep apnea,
thyroid or parathyroid disorders).

Page | 440
Table 6.3. Clinical clues to secondary causes of HTN.

CLINICAL CLUES SUSPECTED CONDITIONS

Abdominal or flank masses, family Polycystic kidney

history of adult polycystic kidney
Abdominal bruits, especially if Renovascular disease
diastolic component is present
Truncal obesity with purple striae Cushing’s syndrome

Tachycardia, tremor, orthostatic Pheochromocytoma

hypotension, sweating, flushing,
pallor
Anemia, edema, azotemia, casts Chronic kidney disease

Pulse deficit, unequal pulses Takayasu’s arteritis,

coarctation of the aorta
Cramps, body malaise, hypokalemia Hyperaldosteronism

Use of contraceptive pills Contraceptive-induced HTN

Neck mass with bruit, lid lag, Thyrotoxicosis
tremors with or without
exophthalmos
Poor BP control with drug therapy Any of the above
Sudden onset of hypertension Any of the above
Sudden deterioration of BP control Any of the above

III. WHAT IS THE APPROACH TO THE TREATMENT OF

HYPERTENSION?

A. Lifestyle Modification

These are the cornerstones of HTN prevention and are likewise equally
important in treatment, and are thus initiated in all patients and
maintained throughout the duration of management.

Page | 441
Table 6.4. Lifestyle modification.

MODIFICATION RECOMMENDATION APPROXIMATE SBP

REDUCTION (Range)

Weight Reductionᵃ Maintain normal body weight 5-20 mmHg/10 kg

(BMI 18.5 – 24.9 kg/m2)ᵇ

Adopt Dietary Consume a diet rich in fruits, 8-14 mmHg

Approaches to Stop vegetables, and low-fat dairy
Hypertension (DASH) products with reduced content
Eating Plan of saturated and total fat.

Dietary Sodium Reduce dietary sodium intake 2-8 mmHg

Reduction to no more than 100 mmol per
day (2.3 g Na or 5 g NaCl –
equivalent to approximately 0.9
teaspoon). This is necessary in
CKD and CHF

Physical Activity Engage in regular aerobic 4-9 mmHg

physical activity, such as brisk
walking (at least 30 min./day;
most days of the week)

Moderation of Alcohol Limit to 30 mL or 28 g of 2-4mmHg

Consumption ethanol/day or no more than 2
drinks (e.g. 720 mL or 2 bottles
of beer, 240 mL or 2 glasses of
wine, or 60 mL or 2 jiggers of
100-proof whiskey) per day to
most men, and no more than 1
drink in women and lighter-
weight men.

Cessation of Smoking It is recommended to give all _

smokers advice to quit smoking
and to offer assistance.
ᵃOverweight patients (excess of >10% of ideal body weight with a waist-hip ratio of >0.9 in males
and >0.8 in females and an abdominal circumference of >90 cm in males and >80 cm in
females) should attempt a weight reduction at a rate of 1.0 lb or 0.5 kg per week.
ᵇWeight reduction can be achieved by regular aerobic activities and total caloric reductions for
which prescriptions can be obtained from a nutritionist. In the absence of one, patients can be
advised to decrease their total caloric intake by 15% .

Page | 442
B. Pharmacologic Treatment

1. When is pharmacologic treatment initiated and what are the BP

thresholds?

The PHA-PSH joint statement divides pharmacologic treatment

into primary and secondary prevention. Primary prevention
pertains to treatment in patients who have no concomitant
cardiovascular disease (CVD) including previous myocardial
infarction (MI), stroke, diabetes mellitus, and renal disease.
Secondary prevention refers to treatment in patients who have
cardiovascular and/or other related co-morbidities. The PHA-PSH
statement also added recommendations for special populations.

The recommendations are as follow:3

a. For primary prevention, in patients with low to intermediate

risk (i.e., with 0 – 2 risk factors), initiate pharmacologic
intervention at clinic BP of 140/90.
• It may also be reasonable to initiate
pharmacologic intervention with an average
reading of home BP monitoring (HBPM) at
135/85.
• For patients at high risk (i.e., with 3 or more risk
factors), initiate pharmacologic intervention at BP
of 130/80.

b. For secondary prevention, initiate pharmacologic

intervention at BP of 130/80.

c. For patients with BP less than 130/80 but with multiple risk
factors, individualize treatment and focus on overall risk
reduction.

d. For the elderly patients (65 – 80 years old), BP thresholds

for initiation of therapy are recommended based on
biological factors (e.g., frailty due to advanced age,
independence, and tolerability of the pharmacotherapeutic
drugs) rather than chronological age alone.

For the fit elderly or those physically active, the BP threshold

is 140/90.

For the frail elderly patients, or those physically inactive, or

with a co-morbid illness, the threshold to initiate
pharmacologic therapy is 150/90.

Page | 443
 2. What are the BP target goals?

a. A BP target goal of less than 130/80 is generally

recommended for all patients if this BP is tolerated. The
details of the current recommendations of the PHA-PSH are
as follows: 3

b. A BP target of < 130/80 is recommended for secondary

prevention or for those who are at high risk for developing
CVD (with 3 or more risk factors).

c. The same target BP of < 130/80 is reasonable for primary

prevention of those patients with low to intermediate risk for
developing CVD (with 0 – 2 risk factors).

d. For older patients aged > 65, when necessary, the SBP may
be targeted to a range of 130 – 139 mm Hg at any level of
CV risks and in patients with or without established CVD.

e. For patients aged over 80 years, a systolic BP target range of

130 – 139 is recommended, if tolerated.

There should be close monitoring and management of

adverse events.

f. A diastolic BP target of < 80 mm Hg is considered for all

hypertensive patients, independent of the level of risk and
co-morbidities.

3. What are the guidelines for the selection of drug therapy?

a. The main objective of hypertension treatment is to attain and

maintain goal BP and to reduce the increased risk of future
cardiovascular events.

b. The choice of antihypertensive agent is directed towards the

most probable pathophysiologic abnormalities or the
presence of compelling indications and contraindications.

c. In most patients, it is recommended to initiate

antihypertensive treatment with a two-drug combination,
preferably in a single-pill combination (SPC). (Refer to the
algorithm).

d. Preferred 2 drug combinations are a Renin-Angiotensin S

(RAS) blocker with calcium channel blocker or a diuretic.

Page | 444
 e. The combination of a beta-blocker with a diuretic or any drug
from the other major classes is an alternative when there is
a specific indication for a beta-blocker, such as angina, post-
myocardial infarction, heart failure, or heart rate control.

f. Use monotherapy in frail older patients and those at low risk

and with grade 1 hypertension (particularly if SBP is < 150
mm Hg).

g. If goal BP is not reached with 2 drugs, add and titrate a third

drug from the list provided (Refer to the algorithm). 1 The use
of a RAS blocker, a CCB, and a diuretic, preferably as an SPC,
is recommended.

h. For resistant hypertension, defined as failure to lower office

(clinic) SBP and DBP values to <140 mm Hg and/or <90 mm
Hg, respectively, despite giving the recommended treatment
strategy, the recommended treatment is the addition of low-
dose spironolactone to existing treatment or the addition of
further diuretic therapy. For the primary healthcare level,
treatment can include a higher-dose thiazide/ thiazide-like
diuretic or a loop diuretic, or the addition of bisoprolol.

i. In some patients on once-daily doses, the antihypertensive

effect may diminish towards the end of the dosing interval.
All physicians should be aware of this TROUGH effect. BP
must be measured just before dosing and adjustment in
dose and frequency may be considered.

Do not use an ACEI and ARB together in the same patients since this
can lead to hyperkalemia or renal failure.

Page | 445
 4. What is the recommended dose of the medication?

Table 6.5. Recommended initial daily and target doses of antihypertensive

agents.a

MEDICATION Initial Daily Target Dose No. of

Dose, mg in RCTs b, mg Dosing per
day
ACE Inhibitors (ACEI):
Captopril 50 150-200 2
Enalapril 5 20 1-2

Angiotensin Receptor
Blocker (ARB):
Losartan 50 100 1-2

Beta Blocker (BB):

Metoprolol 50 100-200 1-2

Calcium Channel Blocker

(CCB):
Amlodipine 2.5 10 1

Thiazide-type Diuretic:
Hydrochlorothiazide 12.5 – 25 25-100 1-2

a Available at the primary healthcare facilities

b Randomized Controlled Trials

Page | 446
 5. What are the choices of drug classes for uncomplicated
HTN and HTN with compelling indications?

Table 6.6. Recommended medicines for the treatment of patients with HTN
associated with compelling indications.

Compelling Indications Diuretic Beta- ACEI ARB CCB

blocker
Uncomplicated HTN     
Heart Failure    
Post MI   
High Coronary    
Disease Risk
Diabetes     
Chronic Kidney * * 
Disease
Recurrent Stroke   
Prevention

* Indicates addition of loop diuretic.

6. What are the contraindications to the use of anti-hypertensive

medications?

a. For Thiazide diuretics, the contraindication will be the

presence of gout.

b. For Beta-blockers, contraindications are asthma, COPD, AV

block (grades 2 and 3), bradycardia, and peripheral
vascular disease.

c. For Calcium antagonists (verapamil, diltiazem),

contraindications are AV block (grades 2 and 3, trifascicular
block), severe LV dysfunction, heart failure, bradycardia.

d. For ACEI – Pregnancy, angioneurotic edema, hyperkalemia,

and bilateral renal artery stenosis.

e. For ARB – pregnancy, hyperkalemia, and bilateral renal

artery stenosis.

Page | 447
 IV. What are the recommendations for patients with Borderline
Hypertension?
For patients with BP in the borderline range (130 – 139 / 85 – 89), lifestyle
modification should be initiated and maintained. Pharmacologic treatment is
considered if these patients have very high risks with cardiovascular disease,
especially coronary artery disease.

V. What is the management for special conditions?

A. Pregnancy

1. What is the recommendation regarding pharmacologic treatment

of chronic hypertension in pregnancy?

Table 6.7. Pharmacologic treatment of chronic HTN in pregnancy.

AGENT COMMENTS

Methyldopa Preferred based on long-term follow-up studies

supporting safety

An alternative drug is Amlodipine at a dose of 5 mg once daily if

allowed by the obstetrician.

!! ACEIs, Angiotensin II Receptor Antagonists are contraindicated

in pregnancy since there are reported fetal toxicity and death with
their use.

B. Elderly Patients

In elderly hypertensive patients, low-dose thiazide diuretics and

calcium channel blockers are the preferred agents. Beta-blockers are
alternative agents. In the very elderly patients up to 85 years old,
treatment and control of HTN are associated with clinical benefits.

In frail elderly patients. monotherapy is the preferred treatment

strategy.

Page | 448
 C. Hypertensive Crises: Emergencies and Urgencies

1. Emergencies

a. Definition: Severe elevations (>180/120 mm Hg)

complicated by evidence of impending or progressive target
organ damage (TOD) that include the following:
hypertensive encephalopathy, intracerebral hemorrhage,
acute MI, acute left ventricular failure with pulmonary
edema, unstable angina pectoris, eclampsia, dissecting
aortic aneurysms, malignant nephrosclerosis, and findings
of papilledema and optic nerve head edema.

!! Patients with hypertensive emergencies must be transferred

immediately to the hospital.

b. Aggressive BP lowering should be achieved immediately

(within minutes to hours) except in patients with ischemic
strokes. Recommended therapy is the use of intravenous
parenteral agents that will allow a more controlled rate of
reduction. These include Nicardipine HCl.

c. Emergency treatment at the RHU or CHO while awaiting

transfer or during transport to the hospital:

i. The initial goal is to reduce mean arterial BP by no

more than 25% within minutes to 1 hour, then, if
stable, to 160/100-110 mmHg within the next 2-6
hours.

ii. Excessive falls in pressure that may precipitate or

aggravate renal, cerebral, or coronary ischemia must
be avoided.

!! Short-acting nifedipine is no longer considered acceptable in the initial

treatment of hypertensive crisis because it can cause excessive falls in
BP.

iii. Nicardipine HCl, when available in facilities capable of

managing its complications, is administered as
intravenous bolus injection using 1 mg dose, with
close BP and cardiac rate monitoring. Other adverse
reactions include tachycardia, headache, flushing,
and local phlebitis.

Page | 449
 iv. Monitor BP and heart rate every 15 to 30 minutes.
!! Oral captopril and clonidine will not provide the desired controlled rate
of BP reduction and may lead to severe hypotension that can precipitate
unexpected myocardial infarct or acute ischemic stroke.
2. Urgencies

a. Definition: Severe elevations of BP without evidence of

target organ damage. The patients present with higher
levels of BP that may be associated with headaches,
shortness of breath, epistaxis, or severe anxiety.

b. These patients may benefit from treatment with short-

acting oral medicines that include captopril and clonidine
(see Table 27). The patients should be observed closely for
several hours at the healthcare facility.

The Council on Hypertension of the Philippine Heart

Association (written communication received August 18,
2014) enumerates the following conditions for treatment of
hypertensive urgencies with oral captopril and clonidine:
BP level of >180 mm Hg systolic or >120 mm Hg diastolic;
in the absence of active target organ damage, and the
absence of external causes of sudden BP elevation such as
stress or severe pain.

b. The appropriate oral antihypertensive agents should be

maintained and control of blood pressure achieved within
3 days. Close follow-up at the center is necessary.

Page | 450
Table 6.8. Captopril and clonidine use in hypertensive urgencies.

Medicine Dose Onset of Action Adverse

(minutes) Reactions

Captopril 25 mg, by 15-30 Hypotension,

mouth, repeat renal failure in bilateral
as required to renal artery stenosis
reach target BP

Clonidine 75 30-60 Hypotension,

micrograms, by drowsiness,
mouth or SL*, dry mouth
repeat every
30-60 minutes
as required to
reach target BP

*Sublingual (SL) Clonidine may be used in fasting patients or in those unable to absorb drugs
through the gastrointestinal route.

VI. What are the causes of resistant HTN?

A. Improper BP measurement

B. Volume overload due to:

1. Excess sodium intake

2. Volume retention from kidney disease
3. Inadequate diuretic therapy

C. Drug-induced or other causes:

1. Nonadherence
2. Inadequate doses (including the frequency of intake per day)
3. Inappropriate combinations
4. NSAIDs; cyclo-oxygenase 2 inhibitors

5. Cocaine, amphetamines, other illicit drugs

6. Sympathomimetics (decongestants, anorexics)

Page | 451
 7. Oral contraceptive hormones
8. Adrenal steroid hormones
9. Cyclosporine and tacrolimus
10. Erythropoietin
11. Selected dietary supplements and medicines (e.g., ephedra, ma
huang, bitter orange)

D. Associated conditions:

1. Obesity
2. Excess alcohol intake

VII. When is a referral to the higher level of care warranted?

Referral to the higher level of care or hypertension specialist is indicated:

1. When goal BP cannot be attained using the above strategies; or,

2. When management of patients with complications needs additional
clinical consultation.

VIII. How often should the patient follow up at the clinic?

Regular follow-up must be emphasized. Patients should follow up at least

once a month. When the goal BP becomes stable, follow-up should be at
least once every 2 to 3 months.

IX. How can HTN be prevented among normotensive patients?

Weight reduction among overweight individuals through moderate physical

activity and reduced total caloric intake decrease the incidence of
hypertension.

REFERENCES:
1 American College of Cardiology and American Heart Association Task Force on
Clinical Practice Guidelines. 2017 Guidelines for the Prevention, Detection,
Evaluation and Management of High Blood Pressure in Adults. J Am C

2 Cunningham FE, Baughman VL, Peters J, Laurito CE. “Comparative

pharmacokinetics of oral versus sublingual clonidine,” (Abstract). J Clin
Anesth, 1994 Sep-Oct, 6 (5):430-3.

Page | 452
3 Joint Position of the Philippine Heart Association and the Philippine Society of
Hypertension on the 2017 ACC-AHA Guidelines for the Prevention,
Detection, and Management of High Blood Pressure in Adults, 2018.

4 Multisectoral Task Force Consensus on the Detection and Management of

Hypertension in the Philippines, 2011, Philippine Clinical Practice
Guidelines on the Detection and Management of Hypertension – 2011 (also
known as the 140/90 Report).

5 National Institutes of Health, U.S. Department of Health and Human Services,

August 2004, The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

6 Philippine Heart Association Council on Hypertension, Position Statement on

Management of Hypertension in Adults, Aug. 18, 2014 (through
communication).

7 Spah F, Grosser KD. “Treatment of hypertensive urgencies and emergencies

with nitrendipine, nifedipine, and clonidine: effect on blood pressure and
heart rate,’ (Abstract). Journal of Cardiovascular Pharmacology, 1988; 12
Suppl 4:S154-6.

8 The Panel Members Appointed to the Eighth Joint National Committee (JNC 8),
February 2014, ‘2014 Evidence-Based Guideline for the Management of
High Blood Pressure in Adults: Report from the Panel Members Appointed
to the Eighth Joint National Committee (JNC 8)’, The Journal of the American
Medical Association, vol. 311, no. 5, pp. 507-520.

9 The Task Force for the Management of Arterial Hypertension of the European
Society of Hypertension and of the European Society, June 2013, ‘2013
ESH/ESC Guidelines for the Management of Arterial Hypertension’,
European Heart Journal, vol. 34, issue 28, pp. 2159-2219.

10 The Seventh Report of the Joint National Committee on Prevention, Detection,

Evaluation, and Treatment of High Blood Pressure. NIH Publication No. 04-
5230. August 2004. National Institute of Health, US Department of Health
and Human Services.

11 Williams B, Mancia G, Spiering W, et.al. 2018 ESC/ESH Guidelines for the

Management of Arterial Hypertension. European Heart Journal, vol. 39,
Issue 1, September 2018, pp. 3021 – 3104.

Page | 453
Page | 454
Page | 455
Page | 456
 Updated Interim Guidelines on the Management of
Type 2 Diabetes Mellitus in Adults at the Primary
Health Care Level
Developed in collaboration with:

Dr. Michael Villa, FPCP, FPSEDM

Philippine Society of Endocrinology, Diabetes, and Metabolism

Dr. Grace de los Santos

Dr. Maria Marci Cruz
Diabetes Philippines

Dr. Marcelo A. Lim

Dr. Elizabeth Ann F. Catindig
Institute for Studies on Diabetes Foundation Inc.

Dr. Carmela Granada

DOH Disease Prevention and Control Bureau

I. What are the recommendations for screening for diabetes

and pre-diabetes?

A. Universal screening using laboratory tests is not

recommended as it would identify very few individuals who are
at risk.

B. However, all individuals being seen at any physician’s clinic or

by any healthcare provider should be evaluated annually for
risk factors for type 2 diabetes and pre-diabetes.

C. Who should undergo screening for diabetes mellitus?

1. All patients with clinical symptoms of diabetes (polyuria,
polydipsia, polyphagia, non-healing wound, pruritus);

Page | 457
 2. All pregnant women;

3. Asymptomatic individuals with any of the following risk factors for

Type 2 diabetes mellitus:

a. Age ≥40 years (NNHES 2004 showed that significant

burden of diabetes begins at age 40 years, approximating
already the national prevalence). Screening individuals as
early as age 40 years in family physicians’ offices have
proved to be useful in detecting unrecognized diabetes.

b. All adults of any age who are overweight or obese are

defined as:

• Overweight: Body Mass Index (BMI)2 of ≥ 23 kg/m2,

where BMI = Weight in kg / Height in m2
• Obese: BMI2 of ≥25 kg/m2, or,
• Waist circumference of ≥80 cm (females) and ≥90
cm (males) (The waist is measured at the point
midway between the most superior portion of the iliac
bone and the inferior edge of the 12th rib. Take the
reading to the nearest 0.1 cm, at the end of normal
expiration or exhalation).
• Waist-hip ratio (WHR)3 of ≥1 for males and ≥0.85 for
females.

c. Any individual with at least one of the following risk factors:

• First-degree relative with Type 2 diabetes

• History of Impaired Glucose Tolerance (IGT) or
Impaired Fasting Glucose (IFG)
• History of Gestational Diabetes Mellitus (GDM) or
delivery of a baby weighing 8 lbs or above
• Hypertension (BP ≥140/90 mmHg)
• Diagnosis or history of any vascular diseases including
stroke, peripheral arterial disease, or coronary artery
disease
• HDL cholesterol <35 mg/dL (<0.9 mmol/L) and/or
triglycerides >250 mg/dL (>2.82 mmol/L)
• Polycystic ovarian syndrome (PCOS)
• Acanthosis nigricans
• Physical inactivity
• Schizophrenia
• Tuberculosis

Page | 458
D. Testing should ideally be carried out within the healthcare
setting (clinics, hospitals, local health centers) because of the
need for follow-up and discussion of abnormal results by
qualified health care professionals (nurse, diabetes educator,
and physician).

E. Testing in any setting should be supervised by a qualified

health care professional.

F. If initial test/s is/are negative for diabetes, then REPEAT

testing should ideally be done annually.

G. What are the standard recommended screening tests for

diabetes?

1. Any of the following tests may be done:

a. Fasting Blood Glucose after an overnight fast for at least 8

hours up to a maximum of 12 hours; or,

b. Two-hour plasma glucose during a 75 g Oral Glucose

Tolerance Test; or,
c. Random plasma glucose.

2. A 75 g OGTT is preferred as the first test in the following

individuals who have: (Grade B, Level 3)

a. A previous FBS showing Impaired Fasting Glucose (100 to

125 mg/dL or 5.6 to 6.9 mmol/L)

b. Previous diagnosis of cardiovascular disease (coronary

artery disease, stroke, peripheral arteriovascular disease)
or who are at high risk for cardiovascular disease.

c. A diagnosis of Metabolic Syndrome

3. Currently, the routine use of the following tests for the diagnosis
of diabetes is not recommended*:

a. HbA1c (due to the non-availability of this test in many areas

and the lack of national standardization)
b. Capillary Blood Glucose
c. Fructosamine
d. Urinalysis (urine glucose)
e. Plasma insulin

Page | 459
 *However, if any of these tests is available upon
consultation due to prior testing, it should be interpreted with
caution and confirmed by any of the 3 tests that are considered
standard, i.e., fasting plasma glucose, oral glucose tolerance
test, or random plasma glucose.

II. When is the diagnosis of Diabetes Mellitus and Pre-diabetes made?

A. Normal blood sugar is defined as:

1. An FBS <5.6 mmol/L (<100 mg/dL); or,

2. Random/ casual blood glucose <7.7 mmol/L (<140
mg/dL); or,
3. 2-hour blood sugar in the 75 g OGTT <7.7 mmol/L (<140
mg/dL).

B. Pre-diabetes is defined as either:

1. Impaired Fasting Glucose (IFG) when there is FBS of 5.6 up

to 6.9 mmol/L (100-125 mg/dL); or,
2. Impaired Glucose Tolerance (IGT): casual blood glucose
of 7.7 up to 11.0 mmol/L (140-199 mg/dL) OR 2-hour
blood sugar in the 75 g OGTT equal to 7.7 up to 11.0
mmol/L (140-199 mg/dL).

C. Diabetes Mellitus (DM) is defined as:

1. Fasting plasma glucose ≥7 mmol/L (≥126 mg/dL) after an

overnight fast for at least 8 hours up to a maximum of 12
hours; or,
2. Two-hour plasma glucose ≥11.1 mmol/L (≥200 mg/dL)
during a 75 g Oral Glucose Tolerance Test; or,
3. A random plasma glucose ≥11.1 mmol/L (≥200 mg/dL) in
a patient with classic symptoms of hyperglycemia (weight
loss, polyuria, polyphagia, polydipsia) or with signs and
symptoms of hyperglycemic crisis.

Page | 460
Table 7.1. Criteria for normal glucose tolerance, pre-diabetes, and DM.

RANGE OF VALUES

CATEGORY FBS 2-HOUR 75 g Random Blood

OGTT Sugar

Normal glucose <5.6 mmol/L <7.7 mmol/L <7.7 mmol/L

tolerance (<100 mg/dL) (<140 mg/dL) (<140 mg/dL)

Pre-Diabetes: 5.6 – 6.9

Impaired Fasting mmol/L - -
Glucose (100-125
mg/dL)
Impaired Glucose 7.7-11 mmol/L 7.7-11 mmol/L
Intolerance - (140-199 (140-199
mg/dL) mg/dL)
Diabetes Mellitus ≥7.0 mmol/L ≥11.1 mmol/L ≥11.1 mmol/L
(>126 mg/dL) (>200 mg/dL) (>200 mg/dL)

D. Among ASYMPTOMATIC individuals with positive results, any of

the three tests should be REPEATED within two weeks for
confirmation.

III. What is the approach to the screening and diagnosis of

Gestational Diabetes Mellitus (GDM)?

A. All pregnant women should be screened for gestational

diabetes mellitus.

B. All pregnant women should be evaluated at the first prenatal

visit for the following risk factors for diabetes mellitus:

1. Prior history of GDM

2. Glucosuria
3. Family history of Diabetes
4. First-degree relative with type 2-DM
5. Prior macrosomic baby
6. Age >25 years old

Page | 461
 7. Diagnosis of polycystic ovary syndrome
8. Overweight/obese before pregnancy
9. Macrosomia in current pregnancy
10. Polyhydramnios in current pregnancy
11. Intake of drugs affecting carbohydrate metabolism.

C. When should screening for GDM be done?

1. High-risk women should be screened at the soonest possible

time.
2. Routine testing for gestational diabetes is recommended at 24
to 28 weeks age of gestation for women with no risk factors.
3. Testing for gestational diabetes should still be carried out in
women at risk, even beyond 24 to 28 weeks of gestation.

D. What tests should be done and how should these be

interpreted?

1. An oral glucose tolerance test (OGTT), preferably the 75 g OGTT,

should be used to screen for gestational diabetes
2. The criteria of the International Association of Diabetes &
Pregnancy Study Groups (IADPSG) should be used to interpret
the 75 g OGTT where any one value meeting threshold is
considered as gestational diabetes.
3. The following tests should not be used for the diagnosis of
diabetes in pregnancy: capillary blood glucose, FBS, RBS, HbA1c,
fructosamine, urine glucose
4. However, if patients already have FBS or RBS at the time of
consultation, thresholds for DM will be the same as non-pregnant
individuals. Those with glucosuria, elevated CBG, or HbA1c
should undergo 75 g OGTT.
5. The threshold for diagnosing gestational diabetes

Table 7.2. Interpreting the 75 g OGTT results.

75 g IADPSG*
OGTT
FBS 92 mg/dL
1 – hour 180mg/dL
2 – hour 153 mg/dL
3 - hour NA
*Any one value meeting threshold is considered gestational diabetes.

Note: The 75 g OGTT and IADPSG for pregnant women are similar
except that 3 tests are done: FBS, 1-hr and 2-hr post-load blood sugar.

Page | 462
IV. What is the approach to the treatment of patients with Type
2 diabetes mellitus in the outpatient setting?

A. Non-Pharmacologic Therapy

All individuals diagnosed to have diabetes mellitus should receive

advice and instruction regarding therapeutic lifestyle changes,
including medical nutrition therapy (dietary modification) and exercise.

1. Diet

a. Advise patients to consume enough calories to maintain

ideal body weight or prevent further weight gain. Monitor
carbohydrate intake using either the plate method or
counting carbohydrate exchanges. Minimize intake of trans-
fat and reduce saturated fat to <7% of total calories. Sugar
alcohols and non-nutritive sweeteners are safe when
consumed within the acceptable daily intake levels.
Patients with diabetes who take alcohol should limit intake
to one drink per day or less for women and two drinks per
day for men. Routine supplementation with vitamins E and
C or chromium is not advised.

Page | 463
 Figure 1. Pinggang Pinoy for healthy Filipinos aged 19 years and above.
(FNRI-DOST)

The Pinggang Pinoy is a new, easy-to-understand food guide that uses a

familiar food plate model to convey the right food group proportions on a per-
meal basis to meet the energy and nutrient needs of Filipino adults.
Individuals with specific health conditions should consult a nutritionist-
dietitian or any health care provider regarding their energy and nutrient needs.
In addition, it is recommended to read the nutrition information on product
labels, to eat less salty, fried, fatty, and sugar-rich foods, and to stay physically
active.

The equivalent portion sizes per meal are described below:

i. The rice and its alternatives should be one (1) serving of any of the
following:
• 1 cup of cooked rice
• 4 pcs. of pandesal, 17 g each

Page | 464
 • 4 slices of loaf bread, 17 g each
• 1 cup of cooked macaroni or spaghetti noodles
• 1 small pc. of root crop (e.g, kamote, kamoteng kahoy, gabi, ubi)
ii. The fish and its alternatives should be 2 servings of any of the following:
• 1 pc. of small size fish (e.g. galunggong)
• 1 pc. of small chicken leg or 1 matchbox size of chicken breast
• 1 matchbox size of meat (e.g. pork, beef)
• 1 pc. of small chicken egg
iii. The vegetables serving should be ¾ cup to 1 cup, either cooked or raw.
iv. The fruits should be 1 serving of any of the following:
• 1 medium size fruit (e.g banana, dalanghita, kaymito)
• 1 slice of big fruit (e.g. watermelon, papaya)
v. Water and other beverages should be 8 or more glasses daily.

Figure 2. Pinggang Pinoy for specific population groups (FNRI-DOST)

Page | 465
Page | 466
Page | 467
Page | 468
Page | 469
Page | 470
 b. Starch refers to rice, bread, noodles/pasta, or corn. Protein
refers to meat, fish, or vegetable proteins such as soybean
(“tokwa” or tofu). Preferred vegetables are green (deep
green) leafy vegetables. The large circle represents the
typical plate of a diabetic where non-starchy vegetables
comprise half of the meal, while starch sources and
proteins (viand) each comprise a quarter of the plate.

c. Patients are advised to follow the following diet rules:

1.) EAT MOST

Use one or more of these foods as the basis of

every meal: Vegetables, legumes, lentils, noodles,
rice, bread, grains, wholegrain cereals, fresh fruit
(non-sweet).

Note that many sauces and preservatives that

are added to these foods are high in salt, sugar or fat,
and should be avoided.

2.) EAT MODERATELY

Have small servings of protein-rich foods e.g.,

fish, seafood, eggs, lean meat, skinless chicken, low-
fat cheese, low-fat yogurt, low-fat milk, nuts.

3.) EAT LEAST

Minimize fats, sugars, salt, and alcohol e.g.,

butter, oil, cream, coconut milk and cream, processed
meat, fried foods, preserved or processed foods,
pastries, sweets, biscuits, soft drinks.

2. Exercise

Advise regular physical activity at least 150 minutes/week

of moderate-intensity aerobic physical activity (50-70% of
maximum heart rate). Examples of exercises include brisk
walking, jogging, cycling, dancing, and swimming.

The physician should assess patients for possible

contraindications to exercise such as uncontrolled hypertension,
severe autonomic or peripheral neuropathy, history of foot
lesions, and unstable proliferative retinopathy. In the absence of

Page | 471
 contraindications, patients are encouraged to perform
resistance training three times per week.

B. Pharmacologic Therapy

The following is the recommended approach to pharmacologic treatment

for Type 2 DM at the primary healthcare level.

For all diagnosed diabetics, classify the level of severity of diabetes

according to the glycemic levels, presence of symptoms, and complications.
Determine how severe the diabetes is, then set the glycemic target goals.
These targets must be individualized for each patient and may change in an
individual over time. In many patients, the following factors require the need
for specific treatment approaches the presence of ASCVD, heart failure,
chronic kidney disease, obesity and other co-morbidities, risk of
hypoglycemia and other safety issues; and the cost of therapy.

1. When is pharmacologic therapy started?

a. For the patients who are asymptomatic with relatively lower

levels of blood sugar (FBS 126 to <140), the advice to undertake
Medical Nutrition Therapy (MNT), physical activity and regular
exercise, and weight reduction is recommended, with an option
of starting pharmacologic therapy with Metformin.

If glycemic targets are not reached within 3 months,

pharmacologic treatment will be started.

b. For the patients who either have higher blood sugars at the onset
or who are symptomatic, one or dual pharmacologic agents as
applicable are started right away (refer to algorithm) since diet
and lifestyle changes are unlikely to achieve the target values.

If glycemic targets are not reached within 3 months,

intensification of pharmacologic treatment (refer to algorithm) is
considered.

c. Treatment responses should be monitored regularly and should

include its impact on efficacy (blood sugar lowering), weight, and
safety.

Take into consideration also the patients who may need a

reduction or discontinuation of their medications. The reasons
for these include the lack of efficacy, higher risks for side effects

Page | 472
 including hypoglycemia, development of co-morbidities, and
aging.

2. Who are the patients ideally referred to internists or diabetes

specialists (endocrinologists or diabetologists)?

a. Individuals with Type 1 DM;

b. Patients with moderate to severe hyperglycemia;
c. Patients with co-morbid conditions e.g., infections, acute
cardiovascular events such as congestive heart failure or acute
myocardial infarction;
d. Patients with significant hepatic and renal impairment; and,
e. Women with diabetes who are pregnant.

3. What is the initial preferred glucose-lowering medication?

Treatment is usually initiated with the biguanide metformin unless

there are contraindications or intolerance to its adverse drug effects,
such as the development of diarrhea, severe nausea, or abdominal
pain; and eGFR < 30 mL/min/1.73 m2.

4. When should combination therapy be considered?

When glycemic targets are not achieved with a given medication at the
maximum effective dose (i.e., the optimal dose or half maximum
dose), anti-hyperglycemic agents from another pharmacologic class
should be added rather than increasing the first drug to its maximum
dose.

5. What are the principles behind combination therapy?

a. A second anti-hyperglycemic agent can be added with the choice

based on the following considerations:
i. amount of HbA1c lowering
ii. hypoglycemia risk
iii. weight gain
iv. patient profile such as dosing complexity
v. presence of renal problems
vi. presence of hepatic problems
vii. other contraindications, and,
viii. age.

b. Combination therapy capitalizes on the complementary actions

of different drug classes.

Page | 473
 6. What agents can be used in combination therapy?

a. When treatment targets are not achieved, other anti-

hyperglycemic agents may be used with metformin in
various combinations.

b. The selection of medication added to metformin is based

on the clinical characteristics and the preference of the
patients.

Important clinical characteristics to be considered include:

i. the presence of established ASCVD;
ii. the presence of other co-morbidities such as
heart failure or chronic kidney disease;
iii. the risks for specific adverse medication effects,
particularly hypoglycemia and weight gain;
iv. safety and tolerability;
v. the burden of treatment and cost as well as
access to the medications are likewise equally
important factors.

c. These anti-hyperglycemic agents (see Table 7.3 for the

listing and the usual doses) include the following:
i. the secretagogues (sulfonylurea) such as
gliclazide,
ii. thiazolidinediones (TZD),
iii. alpha-glucosidase inhibitors,
iv. incretin-based therapies (DPP4 inhibitors and
GLP-1 receptor agonists), and,
v. SGLT2 inhibitors.

Most of these are not currently listed in the PNF but may
be used when clinically indicated.

d. At the primary healthcare level, the only alternative oral

antihyperglycemic agent available is gliclazide. Combining
this with metformin can be done.

e. Special situations: Co-morbidities:

The Philippine Practice Guidelines for Diabetes Mellitus

further recommend the following treatment in these
special situations where co-morbid conditions exist:

i. Among patients with type 2 diabetes who have

established atherosclerotic cardiovascular disease
(ASCVD), sodium-glucose co-transporter 2 (SGLT2)

Page | 474
 inhibitors (if the eGFR is adequate) or glucagon-like
peptide 1 (GLP-1) receptor agonists that have proven
cardiovascular benefits are ideally added to
metformin when these are available to reduce the
likelihood of major cardiovascular events.

The SGLT2 inhibitors include empagliflozin, canagliflozin,

and dapagliflozin. The GLP-1 receptor agonists
include liraglutide.

ii. For patients with ASCVD in whom heart failure co-

exists, or, is of special concern, SGLT2 inhibitors are
recommended.

iii. For patients with type 2 diabetes with chronic kidney

disease (CKD), with or without cardiovascular disease,
consider the use of an SGLT2 inhibitor that is shown
to reduce CKD progression, or, if this is
contraindicated or is not preferred, a GLP-1 receptor
agonist that is shown to reduce CKD progression can
be used.

iv. For patients without cardiovascular disease and in

whom the risk of hypoglycemia is a concern, the
following, when available, may be added to metformin
when there is failure to achieve glycemic targets:
incretin agents DPP4 inhibitors, or GLP-1 agonists, or
SGLT2 inhibitors, or Thiazolidinediones.

7. When and how is insulin therapy initiated?

a. Insulin is started in the following patients:

i. those with severely uncontrolled diabetes with
catabolism;
ii. those with inadequate control using oral anti-diabetic
agents despite maximum tolerated oral hypoglycemic
agents; or,
iii. those with medical conditions which necessitate
insulin administration, e.g., presence of infections,
pregnancy, or during surgery.

b. Dosages and regimen depend on the individual treatment

endpoints. These are adjusted according to the (capillary) blood
glucose monitoring.

Insulin requirements may increase in the presence of renal

impairment and may decrease in hepatic impairment. Dose

Page | 475
 adjustments may be necessary. Dosage requirements may also
be altered by other factors (e.g., infection, stroke, MI, trauma,
pregnancy, and exercise).

Important Note:
A careful review of the proper dosing of the insulin and the safety
of anti-diabetic medicines is mandatory before initiation of the
therapy. For further guidance, refer to the General Guidelines on
Insulin Treatment (see the Medicine and Therapeutic
Information; to Tables 7.5 and 7.6 (Safety and Tolerability of
Antidiabetic Medicines and Types of Insulin); and to Figure 3
(Sequential Insulin Strategies in T2DM).

c. At the Primary Healthcare Level, the following insulins are

available for use:
i. Isophane human insulin/ NPH human insulin
(Recombinant DNA);
ii. Human Regular Insulin; and
iii. Biphasic Isophane Human Insulin 70/30
(Recombinant DNA).

d. Basal Insulin:

Basal insulin is the initial insulin started for patients who fail to
achieve glycemic targets with non-insulin antihyperglycemic drug
therapy. This is the most convenient or easiest to use.

Basal insulin refers to the longer-acting insulin meant to cover

the body’s basal metabolic insulin requirement (regulating
hepatic glucose production).

The usual recommended basal insulin is insulin glargine used

once daily, which, however, is not currently listed in the National
Formulary.

At the primary healthcare level, the intermediate-acting Isophane

human insulin/ NPH human insulin (Recombinant DNA) is
available and can be used. This has a slower onset of action
(approximately 2 hours) with peak activity reached 10 – 12 hours
and a longer duration of action of up to approximately 24 hours.
This can be given on a once or twice-daily dose.

The suggested method for giving isophane/ NPH human insulin

is as follows:
1) the suggested beginning dose is 10 units/day (or,
computed at 0.1 – 0.2 units/ kg/ day) given as a

Page | 476
 subcutaneous injection in the evening, or, in divided
doses given every 12 hours.
2) The subsequent dosing is to be adjusted depending
on the response.
3) A dose of 2 units every 3 days may be added until the
glycemic target of 130 mg/dL is achieved.

Warning!
Isophane human insulin/ NPH human insulin must never be
given intravenously and is not suitable for the emergency
treatment of diabetic ketoacidosis.

e. Prandial Insulin:

Prandial (or pre-meal) insulin is meant to reduce glycemic

excursions after meals.

The bolus insulin is given as additional medication in patients

receiving basal insulin who achieve a target FBS of 130 mg/dL
but with still elevated sugar during the rest of the day. CBG pre-
meals must be monitored for intensive glucose control.

At the primary healthcare level, the Human Regular Insulin is

available for use as the prandial insulin. This can be
administered by subcutaneous or intramuscular injection. The
intravenous route is reserved for situations requiring urgent
treatment (see below).

Methods for giving prandial insulin are as follows:

i. Method 1: Basal insulin + 1 dose of the prandial
insulin to be given at a dose of 4 units before the
biggest meal of the day;
ii. Method 2: Give 0.1-0.2 units/kg/day of the prandial
insulin divided into three doses given before meals.

Regular insulin is also the most appropriate form of insulin for

use in diabetic emergencies (e.g., diabetic ketoacidosis), for fine
control of sugar in serious illnesses, and the peri-operative
period. In these cases, intravenous injection or infusion is given.

f. Pre-mixed or Biphasic Insulins:

Intensified insulin regimens also include the use of a fixed

combination of short-acting and longer-acting insulin (i.e., the
pre-mixed or biphasic insulins). This is given as a subcutaneous
injection usually twice daily. Caution must be exercised due to a
higher risk for hypoglycemia and/ or weight gain.

Page | 477
 At the primary health care level, Biphasic Isophane Human
Insulin 70/30 (Recombinant DNA) is available for use. It is a
fixed ratio premixed formulation that contains intermediate-
acting and short-acting insulin (70% isophane insulin and 30%
soluble insulin).

Warning!
Biphasic isophane human insulin must never be given
intravenously or intramuscularly and is not suitable for the
emergency treatment of diabetic ketoacidosis.

g. When available, the other non-insulin oral antihyperglycemic

agents may be used instead of prandial insulin in the patients
requiring more intensified treatment.

These include the:

i. DPP4 agents (e.g., sitagliptin, saxagliptin, linagliptin,
vildagliptin, teneligliptin); or,
ii. Thiazolidinediones or TZD (e.g., pioglitazone which is
used with precautions due to the risk of causing or
exacerbating congestive heart failure – refer to Table
32 for Safety of Anti-Diabetic Agents).

h. Important Precaution! Insulin must not be given if the patient

fails to take in food or is unable to eat.

i. Patients who are on insulin should be referred to diabetes

specialists (endocrinologists and diabetologists or internists),
especially those who are on multiple-dose insulin injection
(MDII).

8. What are the goals and targets of treatment?

a. The glycemic targets should be reached within 6 months but the

approach to the management of diabetes should remain global,
where the other co-morbidities such as cardiovascular conditions
(e.g., overweight and obesity, dyslipidemia, and hypertension)
are properly and adequately addressed.

b. Ideally, the blood sugar should be monitored using the FBS 2-4
weeks after initiation of therapy. Either an HbA1c every 3-4
months or FBS every 1-2 months is used to assess long-term
glycemic control.

Page | 478
 c. Below are suggested targets for relatively young and newly
diagnosed individuals or individuals who are not at increased risk
for hypoglycemia (see Table 31).

These targets should be individualized based on factors such as

age, the severity of the co-morbid conditions, the overall risk for
hypoglycemia, and the attributes of the medications. These
attributes include risk of inducing hypoglycemia, risk of weight
gain, ease of use, safety impact on hepatic, renal, or cardiac
disease, and cost of treatment.

Table 7.3. Types of anti-diabetic agents and their glycemic efficacy.

ACTION EXAMPLES Amount

DRUG CLASS (Range of doses per of
day) HbA1c
lowering
Sulfonylureas Stimulate Gliclazide (modified- 1-2%
(SUs) pancreatic β-cells release) 30-120
to release insulin mg/day; (immediate-
into the release) 80-320
bloodstream mg/day
Glipizide* 5-20
mg/day
Glimepiride* 1-6
mg/day

Biguanides Decrease the Metformin 500- 1-2%

amount of 2,000 mg/day
glucose made by
the liver
Increase insulin
sensitivity of
muscle and
adipose
Thiazolidinediones Improve insulin Pioglitazone* 15-45 0.5-
sensitivity by mg/day 1.4%
stimulating
PPARγ
Receptors

Page | 479
 Alpha-Glucosidase Block α- Acarbose* 50-100 0.5-
Inhibitors glucosidase mg three times daily 0.8%
(AGIs) enzymes that Voglibose* 200-300
break down mcg three times
complex daily
carbohydrates (after the first
into more spoonful of food)
absorbable
simple sugars

Dipeptyl Inhibits the Sitagliptin* 100 mg 0.5-

Peptidase-IV action of the Saxagliptin* 5 mg 1.0%
Inhibitor DPP4 Linagliptin* 5 mg
(DPP4-inhibitors) enzyme which Teneligliptin* 20 mg
breaks down (per day dosing)
GLP-1, effectively Vildagliptin* 50 mg
increasing the (twice a day)
levels of GLP-1;
causes glucose-
dependent
increase in
insulin secretion

GLP-1 Receptor Stimulate insulin Liraglutide*

Agonist secretion and Dulaglutide*
(GLP-1 RA) reduce glucagon
secretion in a
glucose-
dependent
manner

SGLT2 Inhibitor Enhances urinary Empagliflozin* 10-

(SGLT2i) excretion of 25 mg
glucose Canagliflozin* 100-
300 mg
Dapagliflozin* 10
mg (per day dosing)
Insulins: Anabolic
hormone that
promotes

Page | 480
 peripheral
glucose uptake,
glycogenesis,
lipogenesis and
protein synthesis
of skeletal
muscles and fat
tissue through
the tyrosine
kinase receptor
pathway

• Rapid- acting Insulin lispro*

insulins Insulin aspart*
Insulin glulisine*

• Short-acting Recombinant human

Insulins regular insulin
• Intermediate NPH or Isophane
acting
insulins

• Long-acting Insulin glargine*

insulins Insulin detemir*
Insulin degludec*

• Pre-mixed Human Biphasic

insulins 70/30
Biphasic aspart*
30/70
Biphasic 25 lispro*
75/25
Biphasic 50 lispro*
50/50
Insulin
Degludec/aspart*
70/ 30
*Not included in the 8th Edition of the Philippine National Formulary (2019)
Reference: JL Jameson. LJ De Groot. Endocrinology: Adult and Pediatric, 6th edition.

Page | 481
Table 7.4. Treatment goals for patients with Diabetes Mellitus.

COMPONENTS OF GLOBAL MANAGEMENT TREATMENT GOALS

GLYCEMIC CONTROL :
• FBS 5- 6.1mmol/L (90-110
mg/dL)
• HBa1c <7.0%
• Pre-prandial capillary blood glucose 5-7.2 mmol/L (90-130
mg/dL)
• Peak post-prandial capillary blood <10.0 mmol/L (<180
glucose mg/dL)

BLOOD PRESSURE: <140/80 mmHg

LIPIDS:
• LDL <100 mg/dL (<2.6
mmol/L)
• Triglycerides <1.7 mmol/L (<150
mg/dL)

V. What are the complications of diabetes?

A. Microvascular complications:
1. Retinopathy
2. Nephropathy
3. Neuropathy
4. Autonomic dysfunction, including gastroparesis and sexual
dysfunction

B. Macrovascular complications:
1. Stroke
2. Coronary artery disease
3. Peripheral vascular disease

VI. How is hypoglycemia recognized and treated?

A. Causes of Hypoglycemia

1. Administering too much insulin

2. Missing or delaying meals
3. Exercising or working more than usual
4. Infection or illness (especially with diarrhea or vomiting)

Page | 482
 5. A change in the body’s need for insulin
6. Disease of the adrenal, thyroid gland or progression of kidney or
liver disease
7. Interactions with other drugs that lower blood glucose (e.g., oral
hypoglycemics, salicylates, such as aspirin, sulfa antibiotics, and
certain antidepressants)
8. Consumption of alcoholic beverages.

B. Symptoms of Hypoglycemia

1. Mild to moderate hypoglycemia:

Dizziness
Palpitation
Tremor
Hunger
Restlessness
Tingling in the hands, feet, lips, tongue
Lightheadedness
Inability to concentrate
Headache
Drowsiness
Sleep disturbances
Anxiety
Blurred vision
Slurred speech
Depressive mood
Irritability
Abnormal behavior
Unsteady movement
Personality change

2. Severe Hypoglycemia:

Disorientation
Unconsciousness
Seizures
Death

Page | 483
 Important Note:

The need to recognize these signs and symptoms early and

to act promptly must be emphasized when educating the patients and
their families or caregivers.

Early warning symptoms may be different or less

pronounced under certain conditions, such as long duration of
diabetes, diabetic neuropathies, diabetes in the elderly, use of
medications such as beta-blockers, change in insulin preparations or
intensified control (3 or more insulin injections per day) of diabetes.

C. Treatment of Hypoglycemia

Mild to moderate hypoglycemia is treated by taking in foods

or drinks containing sugar (e.g., half a glass of juice with sugar or
regular soft drinks). Patients should always carry a quick source of
sugar, such as candies.

More severe hypoglycemia may require the assistance of

another person. Patients who cannot take in food or drinks and
unconscious patients need IV administration of glucose at the nearest
medical facility.

Page | 484
Page | 485
 Figure 3. Sequential insulin strategies in T2DM.

Note: Basal insulin is typically started at a dose of 0.2 units/kg per day (e.g.,
50 kg x 0.2 units/kg = 10 units starting dose once a day).

Source: Diabetes Care, Diabetologia. 19 April 2012.

VII. How about herbal medication?

At the moment, it is only Ampalaya (Momordica charantia),

especially the leaves of the Makiling variety, that has some evidence
for efficacy and safety. However, this herbal medication is relatively
less potent than the standard anti-diabetic medications. Thus, they
can only be used by patients who have pre-diabetes or relatively near-
normal blood sugar levels. If used by those with higher blood sugar
levels, it can only be as an adjunct or add-on to standard drugs.

Page | 486
REFERENCES:
Consultative meetings with representatives from the PSEDM and Diabetes
Philippines, April to December, 2019, held at the Pharmaceutical Division,
DOH, Philippine Blood Center, QC.

Davie, MJ, Alessio, DA, Fradkin J, et. Al. “Management of Hyperglycemia in Type
2 Diabetes: 2018. A Consensus Report by the American Diabetes
Association (ADA) and the European Association for the Study of Diabetes
(EASD). Diabetes Care 2018; 41: 2669-2701.

Diabetes Philippines, 2013, ‘Philippine Practice Guidelines on the Diagnosis and

Management of Diabetes Mellitus’, Philippine Pharmaceutical Directory
(PPD) Compendium of Philippine Medicine (CPM), 16th edition, Medicomm
Pacific, Inc., Pasig City, Philippines.

Food and Nutrition research Institute (2014) Pinggang Pinoy. Retrieved January
15, 2020 from https://www.fnri.dost.gov.ph/index.php/tools-and-
standard/pinggang-pinoy.

References cited in the 2013 Philippine Practice Guidelines:

American Association of Clinical Endocrinologists (AACE), 2007.

American College of Physicians (ACP), 2007.
American Diabetes Association Standards of Medical Care (ACE), 2010 and
updates as of 2013.
Canadian Diabetes Association (CDA), 2008.
Diabetes Care, Diabetologia, 19 April 2012.
International Diabetes Federation Global Guideline (IDF), 2005.
Ministry of Health and New Zealand Guidelines Group (NZGG), 2003
National Collaborating Centre for Chronic Conditions (NCCCC), 20

Page | 487
 COMMON POISONING
CAUSTICS: ACIDS
An acid is a proton donor. It generally causes significant tissue
injury at a pH below 3. Aside from pH, other factors that should be
considered when establishing the degree of injury are concentration,
Molarity, volume, contact time, and pre-morbid condition of the
stomach. The acids most commonly encountered in poisoning cases
are:
• Mineral acids (automobile battery acids, toilet bowl cleaners,
and other cleaning agents);
• Inorganic acids (hydrochloric acid, sulfuric acid); and
• Organic acids (acetic acid, formic acid)
Fatalities have been recorded with ingestion of 30 mL of the
following: sulfuric acid 95% (18 M), nitric acid 69% (15 M), and
hydrochloric acid 36% (12 M). However, ingestion of less than 5 mL of
mineral acids is known to have caused death. Non-accidental ingestions
often present with more severe injuries and complications.
Ingestion of acids, except for hydrofluoric acid, produces
coagulation necrosis resulting in eschars which tend to self-limit further
damage. The stomach, primarily the antrum, lesser curvature, and
pylorus, are the common sites of injury. However, the esophagus may
also be affected. Ulceration of necrotic tissues may lead to perforation,
peritonitis, strictures, and stenosis of the esophagus, stomach, or
pylorus.
Table 8.1, Common acids
Common Acids
Acetic Acid
• Permanent wave neutralizers, photography stop bath, disinfectants, hat-
making, printing, dyeing, rayon manufacturing
Boric Acid
• Roach powders, water softener, germicides
Carbolic Acid
• Disinfectants, pharmaceuticals, dyes, plastics manufacturing,
preservatives
Formic Acid
• Airplane glue-making, tanning, deodorizing tablets, plastic menders,
fumigants, embalming fluids
Hydrochloric (muriatic) acid

Page | 488
 • Bleaching agents, metal and toilet bowl cleaners, dye and chemical
synthesis, metal refining
Hydrofluoric acid
• Glass etching, brick cleaning, etching chips in the semiconductor
industry, electroplating, leather tanning, rust removal, cleaning of
porcelain
Nitric acid
• Engraving, electroplating, metal refining, fertilizer manufacturing
Oxalic acid
• Tanning, blueprint paper, disinfectants, household bleach, iron cleaner,
leather, chemical synthesis, anti-rust polish
Phosphoric acid
• Metal and toilet bowl cleaner, rust-proofing
Sulfuric acid
• Automobile batteries, drain cleaners, chemical munitions, fertilizer
manufacturing

Table 8.2. Special precautions

Specific Precautions
• The concomitant intake of alcohol relaxes the pyloric sphincter, thereby
promoting the antegrade progression of acid and production of small
bowel damage and potential perforation.
• Do not insert a nasogastric tube since this increases the risk of
perforation and aspiration pneumonia.
• Do not administer activated charcoal.
• Do not induce vomiting.
• Do not give any neutralizing agent because the reaction can evolve
carbon dioxide which can aggravate the chemical injury to the stomach
and cause rupture.
• The administration of water may result in an exothermic reaction
(release of steam and heat), which aggravates the damage caused by
the strongly acidic solution.
• Acids may also produce systemic manifestations:
o Boric acid – CNS depression including coma cardiovascular
collapse, and renal failure
o Carbolic acid – renal and hepatic injury
o Formic acid – metabolic acidosis and formate poisoning
o Hydrofluoric acid – hypocalcemia, hyperkalemia, hypoglycemia,
cardiovascular symptoms, and CNS symptoms
o Oxalic acid – hypocalcemia and renal failure
o Picric acid – renal injury
o Tannic acid – hepatic injury
• Skin burns should be treated as thermal burns.

Page | 489
 • Endoscopy should be done within 12 hours and not later than 24 hours
after exposure.

Table 8.3. Classification of mucosal injury following caustic substance ingestion

Classification of Mucosal Injury Following Caustic Substance Ingestion
Grade 0 Normal findings on examination
Grade 1 Edema, hyperemia of mucosa
Grade 2a Friability, blisters, hemorrhages, erosions, whitish membranes,
exudates, superficial ulcerations
Grade 2b Grade 2a PLUS deep discrete or circumferential ulceration
Grade 3a Small scattered areas of multiple ulcerations and areas of
necrosis
(brown-black or grayish discoloration)
Grade 3b Extensive necrosis

Page | 490
Page | 491
Treatment of Specific Problems

• ACUTE ABDOMEN: Surgery (if gastrectomy is done, give lifelong Vitamin B12
replacement)

• INFECTION: Start antibiotics; Cover for anaerobes and Gram-negative

organisms

• SHOCK:
o Septic shock
Fluids (isotonic saline)
Appropriate antibiotics
o Hypovolemic shock
Fluid challenge
Acid-base and electrolyte correction
o Neurogenic shock
Pethidine (Meperidine) 1 mg/kg/dose IV

• UPPER AIRWAY OBSTRUCTION:

o Glottic edema
Cricothyroidectomy or tracheostomy
Hydrocortisone 100 mg IV every 6 hours

• UPPER GI BLEEDING: Blood transfusion; Surgery

CAUSTICS: ALKALI – SODIUM HYPOCHLORITE

Sodium hypochlorite is generally used as a household bleach at a
concentration of 3 to 6% (usually ≤5%). Stronger solutions (8% with or without
chlorine) are used for industrial purposes.

At concentrations of 3 to 6%, sodium hypochlorite is a mild to

moderate irritant. It causes eye and skin irritation and can produce mild oral or
esophageal burns. In the stomach, it combines with acids to produce
hypochlorous acid which is an irritant to the mucous membrane but does not
cause stricture formation.

Only minor burns have been reported in children who accidentally

ingest household bleach. However, more serious burns have been observed with
ingestion of higher concentrations of sodium hypochlorite (5 to 7%). In adults,
intentional ingestion of large volumes of sodium hypochlorite may result in
hematemesis and electrolyte imbalance.

Page | 492
Table 8.4. Specific precautions
Specific Precautions
• Do not induce vomiting.
• Do not insert a nasogastric tube. If the patient is received with a
nasogastric tube, leave it in place to avoid possible perforation.
• Do not administer activated charcoal.

Page | 493
Treatment of Specific Problems

• ABDOMINAL PAIN: Pethidine (Meperidine) 1 mg/kg/dose

• ASPIRATION PNEUMONIA:

o Start Penicillin G aqueous, crystalline sodium, or potassium salt after

negative skin test

Adult: 1 to 2 million units every 6 hours slow IV push

Pedia: 200,000 u/kg/day slow IV dose
Page | 494
 o If vomitus is bilous, may require administration of Clindamycin or
Metronidazole.

KEROSENE
Kerosene, an aliphatic hydrocarbon, is the leading cause of accidental
poisoning among children aged six (6) years old and younger. This is because
kerosene, which is commonly used for cooking fuel, is often stored
inappropriately in soft drink bottles or drinking water containers, and placed in
areas that are within reach of children.

The compound is completely absorbed in the gastrointestinal tract

because of its low molecular weight. It can likewise be absorbed through
inhalation and minimally through the skin.

The toxicity of kerosene is due to its local irritating effect and its
systemic effects on various organ systems. It has a high aspiration potential
because of its low viscosity. Thus, close monitoring of the lungs is imperative. The
compound can also depress the CNS, particularly the ventilatory drive, and cause
seizures because of hypoxia. Studies have shown that ingestion of >30 mL with
vomiting, presents a higher risk for the development of pulmonary toxicity.
However, such parameters are not 100% predictive.

Kerosene naturally volatilizes through the esophagus up to the

pharynx. The insertion of a nasogastric tube and the decision to lavage are thus
dependent on the volume ingested and the length of the patient’s esophagus.

Table 8.5. Specific precautions

Specific Precautions
• Do not induce emesis (mechanical or chemical) unless a more toxic
poison is incorporated or ingested along with kerosene.
• Do not use mineral oil or olive oil. The thickened consistency of the
hydrocarbon predisposes to the development of lipoid pneumonia and
enhances hydrocarbon absorption.
• Activated charcoal lavage would not be of benefit unless other toxic
substances (e.g., pesticides) are taken concomitantly.
• It is important to wash the perianal area after a bowel movement since
contact with the stool containing kerosene can produce first- to second-
degree burns on the skin.

Page | 495
Page | 496
Page | 497
 ASPIRATION PNEUMONIA:
o Start Penicillin G aqueous, crystalline sodium, or potassium salt after
negative skin test
Adult: 1 to 2 million units every 6 hours slow IV push
Pedia: 200,000 u/kg/day slow IV dose
o If vomitus is bilous, may require administration of Clindamycin or
Metronidazole.
• GASTRITIS:
o Antacids – aluminum-magnesium hydroxide 30 mL every 6 hours
o H2 blockers (e.g., Famotidine)
Adult: 20 mg IV every 12 hours
Pedia: 0.8 mg/kg/dose every 12 hours
• HYPOPROTHROMBINEMIA:
o Vitamin K
Adult: 10 mg IV up to 60 mg/day
Pedia: maximum of 10 mg/dose
• SEIZURES:
o Diazepam
Adult: 2.5-5.0 mg slow IV push
Pedia: 0.3 mg/kg/dose IV
May be repeated every 2-5 minutes up to 20 mg.
Be ready to intubate the patient before giving additional doses.
o Lorazepam
Adult: 2.5-10 mg/dose repeated twice at intervals of 15-20 minutes
as needed. The usual dose is 4-5 mg/dose.
Pedia: 0.05-0.1 mg/kg/dose IV (max of 4 mg/dose); repeated twice
at intervals of 10-15 minutes as needed.
Compatible with D5W

N-METHYL CARBAMATES
Carbamates inhibit the action of cholinesterase, the enzyme
responsible for the breakdown of acetylcholine to acetic acid and choline. Unlike
the inhibition produced by organophosphates, the binding of the carbamyl moiety
with cholinesterase is reversible. Thus, the clinical syndrome is more benign and
much shorter in duration.

Currently, several agricultural pesticides contain carbamates, such as

benomyl, carbofuran, and carbaryl. Of the household pesticides, propoxur is no
longer a component of commonly used mixed pesticides.

The clinical manifestations of this poisoning resemble those of

organophosphate poisoning except for CNS effects (e.g., convulsions).

Page | 498
 Management is essentially the same with organophosphate poisoning
but does not give oximes. The duration of atropinization is usually shorter, that is,
24-48 hours only, except for poisoning with aldicarb, which is long-acting.
Patients are prone to develop atropine toxicity because of the reversible action
of carbamates.

Table 8.6. Commonly encountered n-methyl carbamates

Commonly Encountered N-Methyl Carbamates
Chemical Hazard Category
Aldicarb Ia
Bendiocarb II
Benomyl IV
BMPC II
Carbaryl II
Carbofuran Ib
Fenobucarb II
Formetanate Ib
Isoprocarb II
Methomyl Ib
Oxamyl Ib
Propoxur II
Thiophanate-methyl IV

ORGANOCHLORINE
Organochlorine pesticides are also known as chlorinated
hydrocarbons. There are three different types: cyclodienes,
dichlorodiphenylethanes, and hexachlorocyclohexanes. Except for Lindane,
which is used as an anti-scabicide, organochlorines are either banned or
restricted by the Fertilizer and Pesticide Authority.

Organochlorines are potent stimulants of the CNS and the sympathetic

system. Cyclodienes, such as endosulfan and chlordane antagonize the
neurotransmitter gaba-aminobutyric acid (GABA) and inhibit Na+–K+ ATPase.
Dichlorodiphenylethanes increase the sensitivity of neurons to small stimuli by
reducing the transport of potassium into the cell, interfering with the transport of
sodium outside the cell, and by inhibiting the actions of ATPase and calmodulin.

Liquid preparations are dissolved in petroleum distillate solvents.

Absorption is through all routes of entry and enterohepatic recirculation occurs
during metabolism. Organochlorines are stored in the fat depot. The half-lives of
these pesticides are relatively long (weeks to years). In the environment,
organochlorines pose potential problems as persistent organic pollutants.
Page | 499
 Table 8.7. Commonly encountered organochlorines
Commonly Encountered Organochlorines
Chemical Hazard Category
Dichlorophenylethanes
DDT II
Cyclodienes
Aldrin Ia
Chlordane II
Dieldrin Ib
Endrin Ib
Endosulfan II
Heptachlor II
Hexachlorocyclohexanes
Lindane II

Table 8.8. Specific precautions

Specific Precautions
• No antidote has been proven effective.
• Do not give sympathomimetic agents (e.g., epinephrine) or a cholinergic
blocker (e.g., atropine) because arrhythmias may occur in a sensitized
heart.
• Do not give fatty liquids, such as broth, milk, and olive oil.
• Phenytoin may be given for the following reasons:
o It enhances cytochrome P450 oxidase system activity, thereby
enhancing organochlorine metabolism
o It acts as both as anti-arrhythmic and anti-convulsant agent

Table 8.9. Clinical features

Clinical Features
• Dichlorodiphenylethanes
Paresthesia, ataxia, abnormal stepping, dizziness, confusion, headache,
nausea and vomiting, fatigue, lethargy, peripheral tremors

• Cyclodienes
Dizziness, headache, nausea, and vomiting, motor hyperexcitability,
hyperreflexia, myoclonic jerks, general malaise, seizures

• Hexachlorocyclohexanes
Tremors, ataxia, convulsions

Page | 500
Treatment of Specific Problems
• ARRHYTHMIAS:
o Phenytoin 10-20 mg/kg IV or PO loading dose then 5-7 mg/kg IV or PO
o If there is no response, add a cardioselective beta-blocker.
o If there is still no response, give 10% calcium gluconate (with cardiac
monitoring).
Adult: 10 mL slow IV
Pedia: 10 mL of 1:5 dilutions
• DERANGED LIVER FUNCTION: Vitamin B complex and glucose (D50/50 + 1
ampul B complex in IV fluid)
• ELECTROLYTE IMBALANCE: Hypokalemia or hypocalcemia; Treat with
potassium chloride or calcium gluconate.
• LOW PROTIME:

Page | 501
 o Vitamin K1 (PHYTONADIONE)
Adult: 10-20 mg IV or IM every 8 hours
Pedia: 1 mg/kg not to exceed 25 mg in 24 hours
• SEIZURES:
o Diazepam
Adult: 2.5-5.0 mg slow IV push
Pedia: 0.3 mg/kg/dose IV
May be repeated every 2-5 minutes up to 20 mg.
Be ready to intubate the patient before giving additional doses.
o Lorazepam
Adult: 2.5-10 mg/dose repeated twice at intervals of 15-20 minutes
as needed. The usual dose is 4-5 mg/dose.
Pedia: 0.05-0.1 mg/kg/dose IV (maximum of 4 mg/dose); repeated
twice at intervals of 10-15 minutes as needed.
Compatible with D5W

ORGANOPHOSPHATES
Organophosphates can be absorbed via ingestion, inhalation, and
dermal contact. They inhibit the action of cholinesterase that is the enzyme that
breaks down acetylcholine to acetic acid and choline.
Effects may appear as early as 10 minutes to as late as two hours
post-exposure, depending on the amount absorbed and route of absorption.
Organophosphates in liquid preparation are usually dissolved in
petroleum distillate solvents, like kerosene and xylene. Isopropanol is another
solvent used together with petroleum distillates. In water-based formulations, the
concentration of isopropanol may be higher.
These solvents produce tachycardia and elevated blood pressure and
therefore may mask the cholinergic manifestations of the organophosphate. Note
that cholinergic effects may be muscarinic, nicotinic, or central, depending on the
amount absorbed.

Page | 502
Table 8.10. Clinical features
Clinical Features
• Mild – mainly muscarinic
Malaise, vomiting, nausea, diarrhea, sweating, abdominal pain,
salivation, miosis
• Moderate – muscarinic and nicotinic
Symptoms of mild poisoning PLUS dyspnea, decreased muscular
strength, bronchospasm, bronchorrhea, speech impairment, muscle
fasciculation, tremor, motor incoordination, bradycardia, involuntary
urination/defecation, muscular cramps, hypotension/hypertension
• Severe – muscarinic, nicotinic and CNS
Symptoms of moderate poisoning PLUS coma, respiratory paralysis,
extreme hypersecretion, cyanosis, sustained hypotension, extreme
muscle weakness, muscular paralysis, convulsion, behavioral changes
Table 8.11. Commonly encountered organophosphates*
Commonly Encountered Organophosphates
Category Ia Category Ib Category II Category III Category
IV
Ethoprophos Dichlorvos/DD Chlorpyrifos Malathion Temepho
Methyl VP Diazinon Primiphos s
parathion Edifenphos Dimethoate methyl
Mevinphos Methamidopho Fenitrothion
Phorate s Fenthion
Phosphamid Methidathion Phenthion
on Monocrotopho Phosalone
Terbufos s
Pyrazophos
Omethoate
Triazophos
*Categories are based on WHO Classification

Page | 503
Table 8.12. Specific precautions
Specific Precautions
• Contraindicated drugs: aminoglycosides, aminophylline, barbiturates,
beta-blockers, furosemide, morphine, phenothiazines, succinylcholine,
sulfonamides, theophylline, and other xanthines, and local anesthetics
especially procaine derivatives
• Do not give IV atropine if the patient is cyanotic as this may cause
ventricular fibrillation in a hypoxic patient. Give atropine IM and correct
cyanosis before IV administration.
• Aggressive treatment must be instituted if there is a history of
concomitant intake of phenothiazine/haloperidol since these drugs
aggravate organophosphate poisoning and increase mortality.
• In case of under atropinization manifested by cholinergic symptoms, re-
atropinize.
• In case of atropine toxicity manifested by behavioral changes, high-
grade fever, flushing of the face, and tachyarrhythmias, discontinue
atropine temporarily or adjust dose/frequency of administration.
Observe and hydrate the patient. Never give any anticholinesterase,
such as physostigmine or neostigmine.
• For arrhythmias, never give beta-blockers or lidocaine. Give calcium
blockers, phenytoin, or bretylium.
• Although furosemide is contraindicated in organophosphate poisoning,
the drug is recommended in cases of pulmonary edema. However,
ensure that respiration is normal and potassium is within acceptable
limits.
• Defer regular diet (e.g., solid foods) until the patient is fully conscious
and atropine dose is already given by oral route. Start with a liquid diet.
• Organophosphates may produce organophosphate-induced delayed
neuropathy (OPIDN) weeks or months after exposure.

Page | 504
Page | 505
Treatment of Specific Problems
• ACIDOSIS: Sodium bicarbonate based on ABG results
• INFECTION:
o Antibiotic specific for the organisms
o AVOID aminoglycosides and chloramphenicol
• PULMONARY CONGESTION: Furosemide 1 mg/kg/dose or Atropine 1 ampul
in 2 mL NSS as nebulization if acute respiratory distress syndrome (ARDS)
sets in, start on positive end-expiratory pressure (PEEP)
• SEIZURES:
o Diazepam
Adult: 2.5-5.0 mg slow IV push
Pedia: 0.3 mg/kg/dose IV
May be repeated every 2-5 minutes up to 20 mg
Be ready to intubate the patient before giving additional doses.
o Lorazepam

Page | 506
 Adult: 2.5-10 mg/dose repeated twice at intervals of 15-20 minutes
as needed. The usual dose is 4-5 mg/dose.
Pedia: 0.05-0.1 mg/kg/dose IV up to a max. of 4 mg/dose repeated
twice at intervals of 10-15 minutes as needed.
Compatible with D5W
o Phenytoin
10-20 mg/kg IV or PO loading dose then,
5-7 mg/kg in 3 divided doses given at 25-50 mg/minute

WATUSI (DANGEROUS FIRECRACKERS)

In 1991, the first documented patient who swallowed an unknown
amount of Watusi died in the emergency room complex of the Philippine General
Hospital.
Watusi, dancing firecracker, or “spit devil” is reddish, thin as a
matchstick, and measures about ½ to 1-inch long. Chemical analysis reveals that
it has the following components:
Table 8.13. Chemical components and toxicity rating of watusi
Chemical Components and Toxicity Rating of Watusi
Chemical Toxicity Rating Lethal Dose
Yellow or white 6 <5 mg/kg
phosphorus
Trinitrotoluene (TNT) 4 50-500 mg/kg
Potassium chlorate 4 50-500 mg/kg
Potassium nitrate 3 0.5-5 g/kg

Page | 507
Table 8.14. Summary toxicities from TNT, Potassium chlorate, and Potassium
nitrate
Summary of Toxicities from Trinitrotoluene (TNT), Potassium Chlorate, and
Potassium Nitrate
TNT Potassium Potassium
Chlorate Nitrate
Lethal dose 50-500 50-500 mg/kg 0.5 to 5 g/kg
mg/kg Adult: 12 g Adult: 2-6 kg
Child: 5 g
Infant: 1 g
Clinical Effects
Hypotension + – +
Nausea and – + +
vomiting
Methemoglobinemi + + +
a
Red cell hemolysis – + +
Aplastic anemia + – –
Subacute hepatic + – –
necrosis

Table 8.15. Clinical stages of acute yellow phosphorus poisoning

Clinical Stages of Acute Yellow Phosphorus Poisoning
Stage 1
Vomiting with or without hematemesis, the severity of symptoms depends on
the amount ingested
Stage 2
Relatively symptom-free period
Stage 3
Severe gastrointestinal symptoms, acute degeneration of liver with
metabolic derangements, significant ECG changes mimicking MI
Table 8.16. Specific precautions
Specific Precautions
• Phosphorus is a protoplasmic poison whose toxicity is enhanced when
dissolved in alcohol, digestible fats, and oils like castor oil.
• Skin or mucosal contact with phosphorus produces painful second and
third-degree burns.
• Yellow phosphorus is insoluble in water but readily soluble in most oils.
• White phosphorus reacts rapidly with oxygen, easily catching fire at
temperatures 10-15 degrees above room temperature.

Page | 508
ETHANOL
Ethanol is a CNS depressant with sedative-hypnotic properties. Acute
overdose of ethanol may lead to respiratory depression, cardiovascular collapse,
and death. It is rapidly absorbed from the upper gastrointestinal tract and is
distributed in the tissues according to their water content.

Page | 509
 The pleasurable effects of alcohol are thought to be mediated via mu-
opioid receptors in the ventral tegmental area, while central effects, such as
ataxia, sedation, and anxiolysis, are mediated through the GABA-benzodiazepine
receptor complex. Glutamate receptor changes, such as NMDA withdrawal and
together with reduced GABA-ergic function, result in increased risk of seizure and
neurotoxicity.
Alcohol is commonly taken with other drugs, particularly drugs of
abuse. The fatal dose is difficult to ascertain because of individual tolerance (the
result of physical dependence and genetic predisposition) but the equivalent of
about 400 mL of pure ethanol consumed in one hour may be lethal.
Patients with blood alcohol levels of 0.05% (50 mg/100 mL) are
considered medically intoxicated. The rate of metabolism is measured in the
blood as 13-15 mg/dL/hour for a non-alcoholic, and greater than 30 mg/dL/hour
for a chronic alcoholic. In cases of intoxication, alcohol follows zero-order kinetics
and metabolism is constant at 100 mg/kg/hour.

Table 8.17. Ethanol content of common alcohol-containing products

Ethanol Content of Common Alcohol-containing Products
Alcoholic Drinks % Ethanol*
Beer
Lager 2–3
Pilsen 5–6
Strong Beer 9 – 14
Wines 7 – 12
Fortified wines (e.g., champagne) 15 – 20
Distillates 40 – 50
(e.g., whiskey, rye, bourbon, rum, gin, brandy, scotch)
Local distilled spirits 60 – 80
(e.g.,) tuba, lambanog
Other Products
Aftershaves 15 – 80
Cold/allergy medications 5 – 16
Cough preparations 2 – 25
Glass cleaners 10
Mouthwashes 15 – 25
Perfumes and colognes 25 – 95
*Proof is numerically twice the percent value

Page | 510
Table 8.18. Common local terms for alcohol drinks and their corresponding
volumes
Common Local Terms for Alcoholic Drinks and their Corresponding Volumes
Alcoholic Drinks Volume
Lapad 325 mL
Bilog 325 mL
Kwatro kantos 325 mL
Long neck 740 mL
Beer grande 1L
Beer (regular) 320 mL

Table 8.19. Clinical features

Clinical Features
Blood Ethanol Clinical Description
Concentration
(mg/dL)
<50 Talkativeness, subjective feeling of well-being
Mild Intoxication: Decreased inhibition, slurred speech,
emotional instability, incoordination, slight visual
impairment, slow reaction time, and increased
confidence
100 – 300 Moderate Intoxication: Ataxia, slurred speech, slight
visual impairment, muscular incoordination, decreased
attention span, altered perception, altered equilibrium,
and diplopia
300 – 500 Severe Intoxication: Vision impairment and double
vision, severe ataxia, and stupor
>500 Very Severe Intoxication: Coma, respiratory failure

Table 8.20. Formula for calculating blood alcohol level

Formula for Calculating Blood Alcohol Level
(mL ingested) x (% alcohol) x (specific gravity of ethanol)
Plasma Level (in mg/dL) = (VD) x (weight in kg) x 10
Where, VD = Volume of Distribution (0.7 L/kg in children and 0.6 L/kg in
adults)
Specific gravity of ethanol = 800 mg/mL

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Table 8.21. Specific precautions
Specific Precautions
• Ethanol enhances the effects of:
anticoagulants (coumadin), antidepressants, antihistamines, hypnotics,
insulin, MAO inhibitors, sedatives, and tranquilizers.
• Disulfiram-like intolerance to ethanol is associated with:
acetohexamide, animal charcoal, calcium carbimide, carbon disulfide,
carbitamide, furazolidone, griseofulvin, imidazoles, metronidazole,
quinacrin, sulfonylureas, thiocarbamates, third-generation
cephalosporins, tolazoline.
• Alcohol with aspirin increases the likelihood of gastrointestinal bleeding.
• Gastric lavage, induction of emesis, and activated charcoal are not
indicated since alcohol is rapidly absorbed from the gastrointestinal
tract. These procedures are indicated only when multiple drug ingestion
is suspected.

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Page | 513
Page | 514
Table 8.22. Alcohol withdrawal syndrome
Alcohol Withdrawal Syndrome
A. Cessation of (reduction in) alcohol use that has been heavy and
prolonged.
B. Two (or more) of the following developing within several hours to a few
days after:
1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than
100)
2. Increased hand tremor
3. Insomnia
4. Nausea and vomiting
5. Transient visual, tactile, or auditory hallucinations or illusions
6. Psychomotor agitation
7. Anxiety
8. Grand mal seizures
C. The symptoms in criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of
functioning.
D. The symptoms are not due to a general medical condition and are not
better accounted for by any other mental disorder.
Specify if: With perceptual disturbances

Table 8.23. Treatment for alcohol withdrawal syndrome

Treatment for Alcohol Withdrawal Syndrome
Pharmacologic Treatment
• Symptom-Triggered Therapy: Start diazepam 5 to 10 mg every 8 hours,
adjusting dose and frequency based on Clinical Institute Withdrawal
Assessment for Alcohol-Revised (CIWA-Ar) Score.
• If there is severe liver dysfunction, drugs metabolized by oxidation (such
as diazepam) are eliminated slowly. In these cases, the “CLOT”
benzodiazepines (clonazepam, lorazepam, oxazepam, and temazepam)
should be used (see Table below).
• Supplementary multivitamins, including thiamine, pyridoxine, and folic
acid
• Maintain euglycemia.
• Potassium, phosphate, and magnesium supplements
Non-pharmacologic Treatment
• Reassurance, reality orientation, personal attention, general nursing
care
• Frequent monitoring of signs and symptoms using the CIWA-Ar Scale

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Table 8.24. Drugs for treatment of acute withdrawal syndrome
Drugs for Treatment of Alcohol Withdrawal Syndrome
Diazepa Lorazepam* Chlordiazepoxi Oxazepam*
m de
Route IV, PO IV, IM, PO IV, PO PO
Initial 5-20 mg 1-2 mg 2x to 15-20 mg 3x to 15-30 mg 3x
dose 3x to 4x 4x a day 4x a day to 4x a day
a day
Liver Oxidatio Glucuronidati Oxidation Glucuronidati
metabolis n on on
m
Active Yes No Yes No
metabolit
e
Half-life Long Intermediate Long Intermediate
(in hours)
Range 20-70 5-25 6-30 5-20
Average 33 15 10 8
*Not available in the Philippines

COBRA BITE
Snake venom contains neurotoxins which can cause paralysis
by blocking the nicotinic acetylcholine receptors at the postsynaptic
motor endplates and/or affecting the mode of neurotransmitter release
at the pre-synaptic motor endplates. Death is due to respiratory failure
as a result of paralysis of the respiratory muscles.
In the Country, there are more than 60 species of snakes,
seven of which are venomous. By far, the most important local snake is
the Philippine cobra (Naja philippinensis).
The Philippine cobra predominantly causes paralysis. Local
tissue injury is uncommon. Neurotoxic signs can appear as late as 24
hours after the bite. The initial evaluation should focus on the local signs
at the bitten area (swelling, blistering, and necrosis), neurologic signs
(ptosis, ophthalmoplegia, followed by dysarthria, poor tongue
protrusion, dysphagia, drooling, limb weakness, depressed or absent
deep tendon reflexes), and respiratory distress which is a sign of severe
envenomation. The available antivenom in the country is specific for
cobra bites. Therefore, it should not be used when envenomation is due
to a pit viper. WARNING: Using a tourniquet, cutting and suctioning the
wound, or applying chemicals have no value, and in fact can be
detrimental to the patient.

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Table 8.25. Specific precautions
Specific Precautions
• Immobilization of the affected limb using pressure bandaging is a
useful technique to reduce venom transport, especially when local
necrotic injury is not evident.
• Patients may develop extreme anxiety and may hyperventilate with
consequent paresthesias and numbness. This may be mistaken as
envenomation.
• When administering the antivenom, extreme caution should be taken
in patients with hypersensitivity to horse serum or who have a history
of atopy.
• Under no circumstances should a skin test be done unless the
antivenom must be administered.
• When administering anticholinesterases, pre-treatment with atropine
should be done to prevent cholinergic side effects, such as
bradycardia and hypersalivation.

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Table 8.26. Actions taken if cobra antivenom is available
If Cobra Antivenom is Available:
• Perform a skin test using 0.2 mL of a 1:100 dilution of the serum with
NSS. Inject intradermally on the extremity opposite the bite and read
after 15 minutes. Observe the patient constantly after the injection. If
no erythema or pseudopodia of the test wheal occurs, the test is
probably negative. Compare with the negative control using NSS 0.2
mL intradermal in the opposite volar area.
• Give 5-10 ampuls (800 IU/amp) IV over 15 minutes (both adult and
pediatric) after negative skin test. Repeat every 1-2 hours until a
response is observed. Alternatively, dilute 5-10 ampuls in 500 mL
isotonic fluid to run for 1-2 hours.
• If with history of allergy, and the condition is life-threatening,
administer diphenhydramine 50-100 mg slow IV before antivenom
therapy, then give slow IV infusion of antivenom. Discontinue after the
first sign of hypersensitivity and manage the reaction using 1:1000
epinephrine 0.5-1.0 mL subcutaneous.
Table 8.27. Actions taken if cobra antivenom is not available
If Cobra Antivenom is NOT Available:
• Pre-treat with atropine 0.6 mg IV.
• Follow with test dose edrophonium chloride 10 mg IV over 1-2 minutes.
• If with positive response, start neostigmine 100 micrograms/kg IV
infusion over 4 hours or 25 micrograms/kg IV push hourly until
reversal of neurotoxic signs is observed.
• If neostigmine is not available, may give pyridostigmine per NGT, 60
mg 1 tablet two to four times a day.

Treatment of Specific Problems

• ACUTE RESPIRATORY FAILURE:
Hook to mechanical ventilator; Pulmonary toilet
• INFECTION: Look for focus of infection; Start broad-spectrum
antibiotics
• LOCAL TISSUE NECROSIS: Debridement; Local wound care,
Antibiotics
• MYOGLOBINURIA: Hydration: 3-4 L per day

PARALYTIC SHELLFISH POISONING

“Red tides” are marine phenomena that usually occur during the rainy
season. They are produced by an overgrowth of dinoflagellates that contain
pigments that are responsible for giving seawater a red-brown appearance. In the

Page | 519
country, the species of dinoflagellates involved are Pyrodinium bahamense var.
compressum and Gymnodinium catanella.
These dinoflagellates contain neurotoxins, particularly saxitoxin,
neosaxitoxin, gonyautoxin, and decarboylsaxitoxin. Generally, these toxins are
found in the digestive glands of mollusks which feed on dinoflagellates.
Paralytic shellfish poisoning (PSP) in humans results from the
ingestion of toxin-containing bivalves. Saxitoxin acts on the peripheral and
autonomic nervous system and blocks depolarization at the neuromuscular
junction by increasing sodium permeability in exchange for potassium efflux. The
most common manifestations occurring within 30 minutes include numbness or
tingling sensation, weakness, and motor incoordination.
Cases have been encountered where shellfish vendors spray their
produce with pesticides to keep away flies and other pests. Diarrhea and muscle
weakness also occur with exposure to organophosphates, a class of pesticides
used frequently in the Philippines. Organophosphate poisoning is therefore worth
ruling out in cases of PSP by determining RBC cholinesterase levels.
Table 8.28. Specific precautions
Specific Precautions
• The toxin is heat-stable. Cooking, frying or baking only partially lower
toxicity. In neurotoxic shellfish poisoning, cooking will not lower
toxicity.
• Do not give laxative or cathartic if diarrhea is present.
• Avoid use of digitalis.

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Page | 521
Treatment of Specific Problems

• ELECTROLYTE IMBALANCES: Correct potassium and other electrolyte

imbalances.
• HYPOVOLEMIC SHOCK: IV fluids, Fluid challenge
• METABOLIC ACIDOSIS: Sodium bicarbonate (1 mEq/kg or based on acid-
base deficit)
• RESPIRATORY DISTRESS: Ventilatory support, Oxygenation

REFERENCE:
Cortes-Maramba NP, Panganiban LCR, Pascual JC, Dioquino CPC, Westergaard
MLS. (Eds.). Algorithms of Common Poisoning, 3rd Editon. National Poison
Management and Control Center, Philippines; 2011.

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 A GUIDE TO THE COMMON PHILIPPINE MEDICINAL PLANTS
FOR THE PRIMARY CARE PROVIDERS

I. What are the General Reminders for the Safe and Proper Use of
Medicinal Plants?

A. Proper Use:

1. Use the correct medicinal plant and the appropriate part of the plant
that is recommended for use.
2. Use these only for the recommended indications.
3. Use only one kind of medicinal plant for a particular type of ailment or
symptom.
4. Use only the recommended amount of the medicinal plant and use only
for the recommended period.
5. Start with low-strength preparations in individuals who are over 65
years of age, or who have a history of hypersensitivity to drugs or other
substances.

B. Tips on Handling Medicinal Plants:

1. If the medicinal plants are to be grown, it is best to grow them

organically, without any pesticides or insecticides.
2. Plant parts are best harvested on sunny mornings. Avoid picking fruits,
nuts, and leaves after heavy rainfall.
3. If drying is required, dry the plant parts in an oven or air-dry them on
screens above the ground. Never dry them on concrete floors.

C. Precautions:

1. Always have the patient consult at the health center or see a doctor,
especially if he has a severe ailment.
2. If the signs or symptoms persist after administration of the medicinal
plant, have the patient consult at the health center or see a doctor as
soon as possible.
3. Ensure that there is always a correct identification of the medicinal
plants to be used. Make sure that you are using the appropriate part of
the properly identified plant or herb.
4. Take extra precautions if the patient has chronic or severe diseases.

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 5. Know the warnings and precautions regarding the specific uses of
medicinal plants. Make sure you always heed these warnings. Educate
the community regarding these precautions and warnings also.
6. Stop the administration of the medicinal plants or herbs immediately if
an untoward reaction occurs.
7. Know the signs and symptoms of toxicity or overdosage and always
watch out for these. Educate your patients or their family members and
caregivers regarding these.
8. Be extra careful when using herb oil.
9. Pregnant women and nursing mothers should not use medicinal plants
or herbs without their doctor’s advice, except in a few instances when
these can be allowed.
10. Children below 2 years of age should not be given medicinal plants or
herbs without the doctor’s advice, except in a few situations when these
can be allowed.

II. What are the Ways of Preparation of the Medicinal Plants?

A. General Recommendations in the Preparation of the Medicinal Plants:

1. Make sure that the parts of the medicinal plants to be used are free of
any insect or other pests, fungus or molds, pesticide residue, and heavy
metals.
2. Always carefully clean the parts of the plants to be used. Wash them well
under clean running water.
3. Use an earthen or clay pot when preparing the decoction. Enameled or
glass pots may also be used. Never use aluminum or stainless steel pots,
pans, and cooking utensils. Boil over low flame or heat. Remove the cover
or lid while boiling.

4. When using dried parts of the plants, use only half of the dosage
recommended for fresh parts (e.g., fresh leaves).

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 5. Decoctions lose their potency with time. Dispose of any remaining
decoctions after one day. To keep these fresh during the day, keep them
lukewarm in a clean, sealed container such as a flask or thermos.

B. Ways of Administration and Preparation of the Medicinal Plants:

1. Pahid (Spread) – Squeeze out the sap or juice extract and apply by
spreading directly on the affected part. Avoid using this if there is pus or
other discharges from the wound.

2. Langgas (Liquid used for washing of wounds) – This is prepared through

decoction, a method of extraction of a plant’s active ingredients by means
of boiling (in water), or gently simmering, the plant material, usually the
tougher ones such as the bark, roots, seeds, woody stems, and rhizomes.

A decoction is also the name of the resultant liquid.

3. Paligo (For bathing) – This is usually a decoction.

4. Mumog (Mouthwash or gargle) – Prepare as a decoction or infusion. An

infusion is prepared by steeping (not simmering) the more delicate parts
of the plants such as the leaves, light stems, or flowers in a liquid (usually
water) to extract the plant’s active ingredients.

An infusion is also the name of the resultant liquid.

5. Tapal (Poultice) – To prepare a poultice, the plant part is finely minced or

crushed into a pulp or made into a paste using additional plant oil. This is
usually directly spread to the affected area. The area may be wrapped or
tied with a piece of clean cloth, gauze or muslin to keep the poultice in
place and keep it from being rubbed off. The poultice can either be warm
or hot (to increase the circulation) or cold (to ease or soothe the
inflammation).

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 6. Inumin (Drink as juice or tea) – Squeeze out the juice or sap; can also be
prepared as a decoction or infusion. Tea is a form of a decoction or
infusion.

III. What are the Common Medicinal Plants of the Philippines?

There are approximately 1,500 medicinal plants in the Philippines.
Unfortunately, only about 120 medicinal plants or 12.5% have been studied
for safety and efficacy.

Ten of these medicinal plants were approved by the Department of Health

(DOH) in 1993 and the Philippine Institute for Traditional and Alternative
Health Care (PITAHC) in 1997.

This section will discuss the medicinal uses and properties of the 10 DOH-
PITAHC endorsed medicinal plants as well as some of the more common
scientifically-validated plants used in the rural areas.

The medicinal properties of the plants are divided into clinical and pre-clinical
properties. Their definitions (From: Research and Development Division,
PITAHC) are as follows:

Clinical properties pertain to properties that were validated after studies

involving human subjects have been completed.

These studies are aimed at determining:

• the safety of a test substance;
• the efficacy of a test substance;
• the determination of the dosage range; and,
• the disposition of the test substance in the human body.

Pre-clinical properties are those that were demonstrated after in vitro and/or
in vivo tests are done to determine the following:
• biological property of a test substance; or,
• toxicological property of a test substance.

The studies on the pre-clinical properties are prerequisites for the clinical
studies.

In the following tables, the scientifically validated uses of the medicinal plants
are listed under the Clinical Properties column or section. The other medicinal
uses that are still under investigation will be seen under the Pre-clinical
Properties. The other traditional or folkloric uses of the medicinal plants are
also included.

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 A. 10 DOH – PITAHC Approved Medicinal Plant (10 Halamang Gamot) and their Uses:

1. LAGUNDI

Scientific Name: Vitex negundo

Common Names: Lagundi, dangla, 5-leaved chaste tree
Bioactive metabolites: Phlobatannins, carbohydrates,
tannins, glycosides, volatile oils, resins, balsams,
flavonoids, and saponins

Medicinal Properties and Preparations

CLINICAL PRE-CLINICAL PROPERTIES

PROPERTIES (Other Medicinal Uses) PREPARATIONS
(Scientifically
Validated Uses)

Antitussive Antimutagenic For cough:

Chop fresh leaves of lagundi, using
Depressant on cardiac function the following quantities:
- For child 2-6 y.o.: 1 & ½
Other traditional uses (Phil tbsp.
Pharmacopoeia, 2004): - For child 7-12 y.o.: 3 tbsp.
- For 13 y.o. and up: 6 tbsp.
• Tonic Then boil in an earthen pot (palayok)
using 2 glasses of water until the
• Febrifuge water is reduced to half.
Leave the pot uncovered while
• Diuretic boiling. Cool then strain. Divide into 3
equal parts and drink 1 part 3 x a
• Anthelmintic day.

• Demulcent

• Astringent

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 2. SAMBONG

Scientific Name: Blumea balsamifera L. (Synonym: Conyza

balsamifera L.)
Common Names: Sambong, alibum, lakdanbulan, subusob,
blumea camphor
Bioactive metabolites: Steroids or 2-deoxysugars,
flavonoids, tannins, polyphenyls, and alkaloids

Medicinal Uses and Preparations

CLINICAL PROPERTIES PRE-CLINICAL PROPERTIES

(Scientifically Validated (Other Medicinal Uses) PREPARATIONS
Uses)

Diuretic Anticancer As a diuretic in edema:

Dissolution of kidney stones
Antihyperuricemic
Antigenoticity
Antimutagenicity
Antimicrobial
Antiobesity
Antioxidant
Other traditional uses (Phil
Pharmacopoeia, 2004):
• For headaches, arthritis,
rheumatism, chest pains
• For gas pains in children
• For gas pains and cough in
children above 7 years old and
adults
Use the decoction.
For kidney stones:
Chop fresh leaves of sambong,
using the following quantity:
- For child 7-12 y.o.: 3
tbsp.
- For 13 y.o. and up: 6
tbsp.
Then boil in an earthen pot
(palayok) using 2 glasses of
water until the water is
reduced to half.
Leave the pot uncovered while
boiling.
Cool, then strain.
Divide the decoction into 3
equal parts and drink 1 part 3
x a day.
Have the patient drink plenty of
water (at least 12 glasses a

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 day) unless this is
contraindicated.

For headaches, arthritis,

rheumatism, chest pains:
Mix crushed leaves with
coconut oil and apply to
affected areas.

For gas pains in children:

Prepare a poultice of crushed
leaves mixed with coconut oil
and apply to the abdomen.

For gas pains and cough in

children above 7 years old and
adults:
Drink the decoction as tea.

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Medicinal Uses and Preparations
CLINICAL PROPERTIES
(Scientifically Validated
Uses)
Adjunct in the
management of diabetes
mellitus type 2 (for non-
insulin requiring
diabetes)
Antimetabolic syndrome
3. AMPALAYA Makiling variety
Scientific Name: Momordica charantia L. (Synonyms:
Momordica balsamina, M. chinensis, M. cylindrica, M.
elegans, M. indica)
Common Names: Ampalaya, amargoso, apalia, palia, paria,
bitter gourd, bitter melon
Bioactive metabolites: Saponins, glycosides, phenolic
constituents, other alkaloids, and 5-hydroxytryptamine
PRE-CLINICAL PROPERTIES
(Other Medicinal Uses) PREPARATIONS
Antibacterial As an adjunct in the control of Type 2
diabetes mellitus:
Anticancer
1. Eat 1 cup of the young
Anti-inflammatory leaves (talbos) 2 x a day
served as a salad or added
Anti-tuberculosis as an ingredient in the
viand. Or,
Analgesic
2. Boil 2 glasses or 2 cups of
Purgative the leaves in 2 glasses of
water until the water is
Anti-viral reduced to half (around 15
minutes of boiling). Cool
Other traditional uses (Phil the decoction. Then, drink
Pharmacopoeia, 2004) 1/3 glass of the decoction
3 x a day, taken 30
• Cough in children minutes before meals.
• Anthelmintic
• For stomach pains
• Antipyretic
• For burns, scalds, and
skin diseases
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 4. GARLIC

Scientific Name: Allium sativum L.

Common Names: Bawang, ajos, garlic
Bioactive metabolites: Alkaloids, flavanoids, saponins,
protein, and carbohydrates, tannins, cardiac glycosides, and
reducing sugars, flavones, and flavonols

Medicinal Uses and Preparations

CLINICAL PROPERTIES PRE-CLINICAL PROPERTIES

(Scientifically Validated Uses) (Other Medicinal Uses) PREPARATIONS

Adjunct in the management Antihyperlipidemic As adjunct to help lower blood

of hyperlipidemia cholesterol level:
Antihypertensive Eat 2 – 3 cloves of garlic (soaked in
Arteriosclerosis vinegar for 30 minutes; blanched in
Fibrinolytic boiled water for 5 minutes; roasted,
Note: or fried in a little amount of cooking
May increase bleeding due to Antiplatelet oil), 3 times a day (taken with
its antiplatelet activity breakfast, lunch and dinner).
Hypoglycemic

Anti-inflammatory Warning:
• Not recommended for dog bites
Antispasmodic or snake bites.
• May increase bleeding due to its
Antimicrobial antiplatelet activity.
(see Precautions/Warnings below)

Side Effects:
• Itchiness or contact dermatitis and asthma may occur as allergic reactions
due to frequent contact with the garlic bulb.
• Headache, myalgia, fatigue, and vertigo
• Abdominal discomfort, nausea, vomiting, heartburn, diarrhea, and a feeling
of fullness
• Body odor and halitosis may occur after continuous use.

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Precautions/ Warnings:
• Not recommended for snake bites or dog bites. The wound should instead
be washed well with soap and water. Then bring the patient immediately to
the health center or hospital.
• Not to be used by nursing mothers.
• Caution when using “bawang” bulb concomitantly with anticoagulants and
antiplatelets due to its effect on platelet aggregation and fibrinogen (Phil
Pharmacopoeia, 2004)

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 5. GUAVA

Scientific Name: Psidium guajava (Synonyms:

Psidium aromaticum, P. cujavus, P. pomiferum, P.
pyriferum)
Common Names: Bayabas, bayagas, bayawas, byabo,
biabas, gaiyabat, guava
Bioactive metabolites: Phenolic compounds,
isoflavonoids, gallic acid, catechin, epicathechin, rutin,
naringenin, kaempferol ascorbic acid, carotenoids
(lycopene, β-carotene, and β-cryptoxanthin), and
glycoside

Medicinal Uses and Preparations

CLINICAL PRE-CLINICAL PROPERTIES

PROPERTIES (Other Medicinal Uses) PREPARATIONS
(Scientifically
Validated Uses)

Gingivitis For “galis” (itchy skin lesions) or For “galis” or wounds with purulent
wounds with purulent discharge discharge:
Acute diarrhea Boil a handful or 2 of the young leaves
For dizziness (talbos) of the guava in a small earthen
Rotaviral pot (palayok). Then cool until
Analgesic lukewarm.
Antidiarrheal Clean the wound using the lukewarm
Antihyperglycemic decoction 2 x a day until the wound
Anti-inflammatory heals.
Antipyretic Have the patient consult at the health
Antimicrobial center or a doctor if there is no relief;
Antioxidant or if fever develops; or, if there is
Antispasmodic erythema around the wound.
Antitussive
Hemostatic effects For dizziness:
Inotropic effects Crush fresh young leaves (talbos) and
place near the nostrils. Have the
Other traditional uses (Phil patient breathe in the aroma of the
Pharmacopoeia, 2004): crushed leaves.

• As wash for the perineal area For cleansing of the perineal area after
after childbirth childbirth:
Boil a handful of the young leaves
• For itchiness (talbos) of the guava in a small earthen
pot (palayok). Then cool.

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 • As astringent Wash the pelvic area using the
lukewarm decoction.

For itchiness:
Boil enough young leaves in an
earthern pot (palayok). Then, cool.
Bathe using the lukewarm decoction.

Precautions/ Warnings:
• Have the patient who has gingivitis consult at the health center, or, a doctor if
there is no relief of the gum swelling, or if fever develops.
• If the wound does not heal, have the patient seek consultation at the health
center or see a doctor immediately

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 6. TSAANG-GUBAT

Scientific Name: Carmona retusa (Synonyms: Ehretia

microphylla, E. buxifolia, E. heterophylla, Carmona
heterophylla, C. microphylla, C. cefusa??)
Common Names: Tsaang gubat, alangit, balingsua, itsa,
putputai, forest tea
Bioactive metabolites: Microphyllone, baurenol, ursolic acid,
dehydromicrophyllone, hydroxymicrophyllone,
cyclomicrophyllone, and allomicro-phyllone

Medicinal Uses and Preparations

CLINICAL PROPERTIES PRE-CLINICAL

(Scientifically Validated PROPERTIES PREPARATIONS
Uses) (Other Medicinal Uses)

Caries/ tooth cavities – Anti-allergy For stomach pains:

preventive
Antidiarrheal Chop fresh leaves of tsaang-gubat,
Antispasmodic using the following quantity:
Antimicrobial - For child 7-12 y.o.: 1 & 1/2
tbsp.
Antimutagenic - For 13 y.o. and up: 3 tbsp.
- Note: Not recommended for a
child < 7 years old.
Then boil in an earthen or clay pot
(palayok) using 2 glasses of water until
the water is reduced to half.
Leave the pot uncovered while boiling.
Cool, then drink.

Have the patient consult a doctor if

there is no relief of abdominal pains.

Precautions/ Warnings:
• Not recommended for children less than 7 years old.
• Have the patient consult at the health unit or a doctor if there is no relief of
the abdominal pains.

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CLINICAL PROPERTIES
(Scientifically Validated
Uses)
Analgesic (Philippine
setting)
(considered as a drug after
human clinical trials)
7. YERBA-BUENA
Scientific Name: Mentha cordifolia (Synonyms:Mentha
agrestis, Mentha arvensis, Mentha campicola)
Common Names: Yerba Buena, hierba Buena,
abelbana, herba buena, hilbas, Karabo, corn
mint, field mint, peppermint
Bioactive metabolites: Tannins, carbonyls, and
flavonoids
Medicinal Uses and Preparations
PRE-CLINICAL PROPERTIES
(Other Medicinal Uses) PREPARATIONS
Antimicrobial For toothaches:
Chop fresh leaves of yerba buena,
Antiparasitic using the following quantity:
- For child 2-6 y.o.: 1 & ½
Antineoplastic tbsp.
- For child 7-12 y.o.: 3 tbsp.
Other traditional uses (Phil. - For 13 y.o. and up: 6 tbsp.
Pharmacopoeia 2004): Then boil in an earthen or clay pot
• For gaseous distention (palayok) using 2 glasses of water
• Cough until the water is reduced to half.
• Fainting Leave the pot uncovered while
• Hysteria boiling.
• Arthritis Cool then strain.
Divide the decoction into 2 parts.
• As a mouthwash Drink 1 part and follow this with the
(decoction) 2nd part after 3-4 hours if the
toothache persists.
Consult at the health center if
symptoms continue to persist.
For headaches:
Page | 539
 Crush fresh leaves and rub or
massage juice extract (katas) on the
forehead and both temples (sentido).

Precaution:
Have the patient consult at the health
center, or a doctor if headaches
persist, or, are accompanied by fever,
vomiting, drowsiness, or other
neurological symptoms.

Side Effects:
• Irritation of the fingers due to the volatile oil (occurs in those who pick large
amounts of the fresh leaves and leafy tops using the bare hands).

8. NIYUG-NIYOGAN

Scientific Name: Quisqualis indica (Synonyms: Quisqualis glabra, Q.

pubescens, Q. spinosa)
Common Names: Niyug-niyogan, sagis, tagisi, Rangoon creeper
Bioactive metabolites: Quisqualic acid, anthelmintic
tannins, rutin, pelargonidin-3-glucoside, and 25-O-
acetyl-23,24-dihydro-cucurbitacin

Page | 540
 Medicinal Uses and Preparations

CLINICAL PRE-CLINICAL PROPERTIES

PROPERTIES (Other Medicinal Uses) PREPARATIONS
(Scientifically
Validated Uses)

Anthelmintic Antipyretic For deworming:

Antihyperlipidemic
Anti-inflammatory
Other traditional uses
(Phil. Pharmacopoeia
2004):
• For diarrhea
Collect the seeds of niyug-niyogan from an over-ripe
(magulang) fruit that has been dried.
Eat the seed as follows: chew very well, then drink ½
to 1 glass of water.
The number of seeds to be eaten depends on the
age of the patient:
- For a child 4-6 y.o.: give 4-5 seeds;
- For a child 7-12 y.o.: give 6-7 seeds;
- For a patient 13 y.o. and above: give 8-10
seeds.
Precautions:
• Do not eat more than the recommended amount.
• Always watch out for side effects (see below).
For fever:
Use roasted seeds

For diarrhea:
Use roasted seeds

Side Effects:
• Abdominal pains, diarrhea, abdominal distention, hiccups (likely to occur if the seeds are
eaten on consecutive days or when several fresh seeds are eaten at one time).
• Dizziness
Precautions/ Warnings:
• Do not eat more than the recommended amount.

9. ACAPULCO/ AKAPULKO

Scientific Name: Senna alata (Synonyms: Cassia alata, C.

bracteata, Herpetica alata))
Common Names: Akapulko, andadasi, bayabasin, kapurko,
katanda, ringworm shrub or bush,
Bioactive metabolites: Alkaloids, lectins, glycosides, and
isoflavones

Page | 541
 Medicinal Uses and Preparations

CLINICAL PROPERTIES PRE-CLINICAL PROPERTIES

(Scientifically Validated (Other Medicinal Uses) PREPARATIONS
Uses)

Antifungal Anti-allergy As anti-fungal (for “an-an, buni,

hadhad o alipunga”):
Anti-scabies Anthelmintic
Mince or pound enough amount of
Mosquito repellent the fresh young leaves of acapulco.
Apply the juice extract (katas) on the
Insecticidal affected skin and massage or rub 2 x
a day. Continue every day for 3
Snake bites weeks.

Other traditional uses (Phil. Note: If with an allergy to the juice

Pharmacopoeia 2004):
• As a laxative
extract of the acapulco, do the
following alternative therapy:
Boil 1 glass of the minced fresh
leaves in 2 glasses of water until the
water is reduced to half. Wash the
affected skin 2 x a day for 3 weeks.

As a laxative:
Use leaflet

Page | 542
 10. ULASIMANG-BATO / PANSIT-PANSITAN

Scientific Name: Peperomia pellucida (Synonyms:

Mipellucidum Piper exiguum)
Common Names: Ulasimang-bato, pansit-pansitan, ikmo-
ikmohan, olasiman halas, sahica puti, sida-sida, sinew-
sinaw, tangon-tangon, shiny bush, clear weed
Bioactive metabolites: Flavonoid compounds, tannins,
saponins, steroids, monoterpenes and sesquiterpene

Medicinal Uses and Preparations

CLINICAL PROPERTIES PRE-CLINICAL PROPERTIES

(Scientifically Validated (Other Medicinal Uses) PREPARATIONS
Uses)

Adjunct in the Analgesic As adjunct in the management of

management of gout gout:
Antibacterial
Antibacterial Eat 1 cup of the talbos or young
Antihyperuricemic fresh leaves (these should not be
Anticancer tightly packed) 3 x a day, served as a
Anti-inflammatory salad.
Antioxidant Or,
Anti-oxidant Boil 1 & ½ glasses, or 3 cups,
(leaves should not be tightly packed),
in 2 glasses of water until the water
Other traditional uses (Phil. is reduced to half (about 15 minutes
Pharmacopoeia 2004): of boiling). Drink ½ glass of the
decoction 3 x a day before eating.
• For pimples
For rheumatic pains:
• For boils or abscesses Use infusion or decoction

For pimples, boils, or abscess:

Use as poultice

Page | 543
 B. Other Common Medicinal Plants Endorsed by PITAHC:

MEDICINAL IMAGES USES AND PREPARATIONS

PLANT AND COMMON NAMES PRECAUTIONS/
SCIENTIFIC WARNINGS
NAME

LUYANG Clinical Property: For dyspepsia:

DILAW Rhizomes: Boil 1 tbsp. of minced
Dyspepsia rhizome (lamang-ugat) of
Curcuma longa the luyang dilaw in 1
Pre-Clinical Properties: glass of water until the
(Synonym: Rhizomes: water is reduced to half.
Amomum Anti-inflammatory Cool and strain.
cucurma, Anticancer For children, 7-12 years
Cucurma For gall bladder stones old, use only half of the
domestica) For fatty liver adult dose.
Lowers bad cholesterol
Contains and triglycerides For sprains, “sakit
curcumin and ngulot,” body aches, or
curcuminoid Turmeric powder: rheumatism (“rayuma”):
Anti-inflammatory, anti- Mince or crush a
Luyang dilaw, dilaw, cancer, antioxidant & sufficient amount of the
dulaw, kalawag, immunostimulatory rhizome (lamang-ugat).
pangar, pangas effects: activity against Rub or massage the
turmeric Alzheimer’s disease affected areas with the
sap or juice.
Warning:
The minced or crushed
luyang dilaw is not
recommended for snake
bites. A snakebite is an
emergency condition.
Wash the bite wound well
with soap and water and
immediately bring the
victim to the health
center or hospital.

LUYA Clinical Properties: For rheumatism

For osteoarthritis (“rayuma”):
Zingiber Mince enough amount of
officinale Anti-inflammatory the fresh lamang ugat ng
luya. Rub or massage the
(Synonyms: For nausea and affected joint with the
Amomum vomiting/ anti-emetic minced part. The heat
zingiber, from the minced ginger
Zingiber Pre-Clinical Properties: will give relief to the
blancoi) Anti-emetic pains.

Anti-inflammatory
Cholagogic
Page | 544
 Other traditional uses For dizziness:
(Phil. Pharmacopoeia Chew then swallow a
2004): small portion of the luya
• Antitussive (1 gram of the dried
• Expectorant ginger) 30 minutes
• Antidyspepsia before traveling or riding
• Carminative (relieves a vehicle.
flatulence)
For cough or colds:
Adverse Reactions: Mince or crush 3 pieces
Contact dermatitis of ginger (laman ng luya)
among sensitive with each piece
individuals approximately the size of
the thumb. Boil these in
Warning: 2 glasses of water until
Luya, laya, agat, ginger The minced or crushed the water is reduced to
luya is not recommended half.
for snake bites. A snake Divide the decoction into
bite is an emergency 3 parts and drink 1 part
condition. Wash the bite 3 x a day.
wound well with soap For children, 7-12 years
and water and old, use only half of the
immediately bring the adult dose.
victim to the health
center or hospital. For abdominal
bloatedness (“kabag”) or
indigestion (“impatso’):
Mince 1 piece of the
laman ng luya,
approximately 4-8
grams.
Boil this in 1 glass of
water until the water is
reduced to half.
Cool then drink.
For children, 7-12 years
old, use only half the
adult dose.

For headaches:
Apply minced luya on the
forehead. You may tie a
piece of cloth around the
head to hold the minced
ginger in place.

Page | 545
 MALUNGGAY
Clinical properties: As lactagogue:
Moringa Studies show Young leaves are boiled
oleifera Lam. chemopreventive and eaten to increase
(Synonyms: potential against cancer breast milk of nursing
Moringa Antimicrobial mothers.
polygona, M. Antioxidant
pterygosperma, Antiasthma For malnutrition:
Guillandina Antihypercholesterolemic Eat cooked leaves
moringa) Water purification
Vitamin A supplement For “galis”, sores and
ulcers:
Pre-Clinical Properties: Decoction of boiled roots
Leaves: or bark is used to wash
Lactagogue galis, sores, and ulcers.
Seeds:
Asthma For constipation:
Malunggay, arunggay, Eat 1 – 2 cups of boiled
dool, kalamungai, For malnutrition: leaves at supper time
kalungai, marungay, Contains all the vitamins, with plenty of water.
malunggue, Ben oil minerals, most amino
tree, horseradish tree, acids and anti-oxidants For good digestion:
moringa needed daily. To treat and avoid
Young leaves are a rich constipation (pagtitibi),
source of calcium, iron, make it a habit to eat
phosphorus, Vitamins A leaves and young fruits
B, and C of the malunggay, as
well as other vegetables
• For galis, sores and and root crops rich in
ulcers fiber.
• For constipation
• For good digestion For rheumatism:
• For rheumatism Massage oil with
powdered roasted seeds
on the affected areas.
Warning:
•The roots of the
malunggay have a toxic
component. Do not use
the roots as an
ingredient when cooking
or as a flavoring.
• The minced or crushed
luya is not recommended
for dog or snakebites.
This is an emergency
condition. Wash the bite
wound well with soap
and water and
immediately bring the
victim to the health
center or hospital.
•The use of the roots to
induce menstruation can

Page | 546
 be dangerous. The
absence of menstruation
may be due to
pregnancy. The use of
the roots may be
dangerous to the
pregnant woman or to
the fetus.

BANABA Clinical Property: For diabetes:

Diabetes The following has been
Lagerstroemia used: decoction of old
speciosa L. Pre-Clinical Properties: leaves and dried fruit
(Synonyms: L. Antihyperlipidemic (dried for 1 – 2 weeks)
flos-reginae, L. using 50 grams to a pint
reginae, Antihyperuricemic of boiling water, 4-6
Munxhausia cups daily have been
speciose) used.
Folkloric use:
As a mouthwash for oral Folkloric use:
sores Use as mouthwash:
Used to cleanse or wash Use leaf decoction
wounds

Important Note:
However, the use of a
decoction of the leaves,
bark, or fruit for diabetes
still needs detailed
studies.

Important Note:
Banaba, agaro, The use of a decoction of
bugarom, makablos, the leaves, bark, or fruit
mitla, nabulong, as a diuretic, or for
pamalauagon, crepe kidney disease still
myrtle, Queen’s flower needs detailed studies.

Precautions:
Avoid intake of the
banaba in:
pregnant women,
nursing mothers,
children, and
those with hypoglycemia

Page | 547
 TAKIP-KOHOL Clinical Properties: For wound healing or
bruises:
Centella Wound healing Eaten as a salad to
asiatica stimulate appetite;
Anti-ulcer Minced or pounded
(Synonyms: Antioxidant (against takipkuhol leaves used
Centella human breast cancer, as a poultice for bruises
boninensis, mouse melanoma, or boils;
Glyceria and rat glioma cell lines) Decoction is used for
asiatica, “galis” or wounds with
Hydrocotyle Neuroprotective purulent discharge.
asiatica)
Pre-Clinical Properties:

Venous insufficiency/
Venous hypertension
Generalized anxiety
disorder
Takip-kuhol, takip-suso, Memory enhancer
hahanghalo, panggaga,
yahong-yahong, tainga-
daga, tagaditak, gotu
kola, pennyworth

SILING-
LABUYO Clinical Properties: For arthritis (“rayuma”),
Leaves: antibacterial, body pains, “pilay,” or
Capsicum anthelmintic insect bite:
frutescens L. Crush mature fruit, mix
Fruits: Antimicrobial with vegetable oil and
(Synonym: Anti-inflammatory apply on the painful
Capsicum Anti-gastric acid areas.
annuum, C. secretion
conicum, C. clastogenic Use for nutrition:
globosum) The fruit is rich in
Pre-Clinical Properties: Vitamins C and A. It has
Contains Analgesic (traditionally moderate amounts of
capsaicin, a used for toothache, iron and Vitamin B.
powerful arthritis and Young leaves (talbos):
phytochemical rheumatism) Very rich in Vitamin A,
Fruits: analgesic, anti- rich in Vitamin C and
oxidant calcium, and with a
moderate amount of iron
Folkloric Use: and Vitamin B.
For “galis” (pruritic skin
lesions) For “galis:”
Pounded or minced
leaves are used as
poultice that is applied
to wounds.

Page | 548

Siling-labuyo, chileng-
bundok, katumbal,
siling-palai, silit-diablo,
chili pepper, cayenne
pepper
Precaution:
Higher risk for gastric
cancer (in high-level
consumers)

BALBAS-PUSA
Clinical Properties: For hypertension:
Orthosiphon Use leaves
aristatus Antihypertensive
(Synonyms: For painful urination
Clerodendrathu Antioxidant (“balisawsaw”), kidney
s spicatus, Anti-inflammatory diseases, or as a
Orthosiphon Antimicrobial diuretic:
spiralis) Antihyperglycemic Use decoction of leaves

With high According to ASEAN:

potassium Boil a handful (15
content and a Pre-Clinical Property: grams) of the leaves in 2
bitter alkaloid, Kidney diathesis glasses of water. Drink
orthosiphonin the decoction once a day
plus daily.
methylpariochr Folkloric uses (Phil
omena A Medicinal Plants, 2018):
For gout and kidney
disorders
Diuretic

Source: Stuart, G.
Philippine
Medicinal Plants.

Balbas-pusa, kabling-
parang, kabling-gubat,
Cat’s whiskers, Kidney
tea plant

COCONUT Clinical Properties: For dry skin:

Coconut meat: Apply the coconut oil on
Cocos nucifera Antimalarial property dry skin after bathing
(Synonym: Coconut oil:
Cocos indica, Antimicrobial For atopic dermatitis:
Cocos nana) Antioxidant

Page | 549
 Reduces plasma total Apply coconut oil or
Coconut oil cholesterol and LDL- Virgin Coconut Oil (VCO)
contains lauric cholesterol on the lesion
acid Hepatoprotective activity
which has Wound-healing property For dehydration due to
antibacterial, Endocarp: diarrhea:
antiviral, and Vasorelaxant activity For adults: drink the
antifungal Husk (mesocarp): coconut water from the
properties Antimicrobial “bunga” that are 7-9
Analgesic months old. The amount
Anti-inflammatory given is equivalent to the
Antioxidant amount of fluid lost due
Antineoplastic to diarrhea.
For infants and young
Bark: children: To each glass
Antiparasitic of coconut water, add 1
Niyog, Lubi, iniug, (anthelmintic) glass of clean water and
punlaing, Coconut Spadix: I teaspoon of sugar and
Antidiabetic a pinch of salt.
Cardioprotective Note:
If diarrhea persists or
Pre-Clinical Properties: worsens, have the
Coconut oil: patient consult
For dry skin, atopic immediately at the
dermatitis, high health center.
cholesterol, infant
developmental/neonatal
care (from effect of For good digestion:
massage on growth To treat and avoid
velocity and constipation (pagtitibi),
neurobehavioral make it a habit to eat
development), coconut meat, fruits and
pediculicidal, HIV vegetables, and root
infection crops rich in fiber.

Coconut water:
Dehydration, diarrhea,
hypertension, anti-
inflammatory, kidney
stones

Coconut flour:
For diabetes

TAWATAWA
Clinical Properties: For bruises, boils, and
Euphorbia hirta Roots: insect bites:
Linn. Antimicrobial, Use the minced or
(Synonyms: antineoplastic pounded leaves as a
Chamaesyce Leaves: poultice.
hirta, Euphorbia Antimicrobial,
gemella) Antiparasitic, For “rayuma”:
Anti-inflammatory, Use the minced or
Antidiarrheal, pounded leaves that are

Page | 550
 Diuretic mixed in vegetable oil as
Whole plant: a poultice.
Antimicrobial,
antioxidant, antiparasitic

Traditional Uses:
For bruises, boils, and
insect bites

For joint pains (rayuma)

Tawatawa, gatas-gatas,
bobi, bolobotonis, For maintenance of good
magatas, pansi-pansi, nutrition:
tababa The leaves of tawatawa
are very rich in Vitamins
A and C and iron. These
are also rich in calcium
and have moderate
amounts of Vitamin B
and fiber.

NOTE:
* Research on its use in
dengue and asthma is
still ongoing.
* Its use for stomach
diseases, for diuresis, for
“buni,” amebiasis,
malaria, dysentery and
intestinal parasitism are
likewise still being
investigated.

Precaution:
The use of tawatawa
tapal or its juice extract
is not recommended for
sore eyes. The eyes may
become infected.

OREGANO For cough For cough:

Place a few leaves (3
Plectranthus Traditional Uses: leaves for adults and 1
amboinicus For headaches leaf for children) on top
(Synonyms: of rice that is almost
Coleus For bloatedness (kabag) cooked. Allow the leaves
amboinicus, to be steamed the
Majana For burns and wounds extract the juice. This
amboinica) can be mixed with sugar
Precaution: or honey.
The use of the juice or its
sap is not recommended

Page | 551
 for sore eyes. The eyes For headaches and
may become infected. bloatedness:
Use as tapal (poultice)

For burns and wounds:

Apply as pahid.

Suganda, bildu, clavo,

latai, oregano

IV. What are the Possible HERB-DRUG Interactions?

(Source: G. U. Stuart, Jr. Phil Medicinal Plants, June 2019)

• Ampalaya - antidiabetic synergism with metformin and glibenclamide

• Banaba – interacts with anti-diabetes medications (may cause blood sugar
to become too low when taken together with antidiabetic medications)
• Bawang – known to have anti-platelet properties; may alter metformin
pharmacokinetics with increased availability
• Luyang-dilaw (turmeric) – may slow blood clotting and if taken with
anticoagulants, may increase the risk for bleeding or bruising
• Lagundi – may decrease the plasma concentration of paracetamol
• Luya – may affect anticoagulation therapy and medicines for hypertension
• Malunggay – contains moringinine, a hypotensive component
• Ulasimang-bato (pansit-pansitan) – hypotensive effect and CYP450 enzyme
inhibitory effect

REFERENCES:

Dayrit FM, Macahig RAS. Encyclopedia of Common Medicinal Plants of the Philippines. Volume 1. Quezon
City: Philippine Institute of Traditional and Alternative Health Care, 2014

Department of Health. Herbal Medicine Plants Approved by the DOH.Manila: DOH, Undated.

Galang RM, Naynes RS, Quiroga CO, Singular JEJr, Sia IC (eds). Patnubay sa Paggamit ng Halamang
Gamot. Quezon City: PITAHC, 2017.

Page | 552
Galvez-Tan JZ, Sia IC. The Best 100 Philippine Medicinal Plants. Quezon City: Health Futures Inc, 2014.

Bureau of Food and Drugs. Philippine Phamacopoeia 1 (PP 1). 1st Ed., Alabang, Muntinlupa: Department
of Health-Bureau of Food and Drugs, 2004.

Principe EB, Jose, AS. Propagation and Management of Herbal and Medicinal Plants. Research
Information Series on Ecosystems Vol. 1, No. 2, May – August, 2002.

PITAHC Research and Development Division, Directory of Herbs. Quezon City: PITAHC, 2017.

Sia, Isidro C. 2020, August 27. Halamanan sa Paso [Power Point slides]. Slide Share.

Stuart G.. Philippine Medicinal Plants. Updated 2019. Accessed 9/22/2020 from
www.stuartxchange.org

Tips on Handling Medicinal Plants/ Herbs. Business Diary Ph. Manila. Accessed 9/21/2020 from
businessdiary.com.ph.

Zabat, PM. Plants Approved by DOH. Centro Escolar University. Boy, HIA, Rutilla, AJH, Santos, KA, et.al.
Recommended Medicinal Plants as Source of Natural Products. Digital Chinese Medicine, Vol. 1,
Issue 2, pp.131-142, Science Direct. Accessed 9/21/2020 from
https://doi.org/10.1016/S2589-3777(19)30018-7

SOURCES OF IMAGES/ PICTURES:

Lagundi, sambong, guava, malunggay, luya, luyang dilaw, coconut, yerba buena, oregano, banaba leaf,
balbas-pusa, siling labuyo, bawang, ampalaya, ulasimang bato (pansit-pansitan), poultice, palayok:
Buenaflor, Joseph Alvin O.

Niyog-niyugan, tawatawa, takip-kohol:

Copyright-free images from the internet

Banaba flower, balbas-pusa flower:

Stuart, Godofredo. Philippine Medicinal Plants. Updated 2019. Accessed 9/22/2020 from
www.stuartexchange.com.

Page | 553
 DIRECTORY

DEPARTMENT OF HEALTH
Website: http://www.doh.gov.ph/
Phone Number: (02) 651-7800

DOH – Antimicrobial Resistance Surveillance Program (ARSP)

Antimicrobial Resistance Surveillance Reference Laboratory
DOH Compound, Filinvest Corporate City, Alabang, Muntinlupa
Website: www.ritm.gov.ph/ www.arsp.com.ph
Phone Number: (02) 8099763 / (02) 8072631 local 241 or 242
Email address: secretariat@arsp.com.ph

DOH – Pharmaceutical Division

Website: https://pharma.doh.gov.ph/
Phone Number: (02) 8-875-7734 local 253
Email Address: pnf@doh.gov.ph

PHILIPPINE FOOD AND DRUG ADMINISTRATION

Email Address: fdac@fda.gov.ph
Website: https://www.fda.gov.ph/

Mobile:
GLOBE/ TM: SMART:

0956-4518268 0961-6804447
0956-4518341 0951-1311186
0977-6177991 0961-0574926
0961-0574927
0961-7709691

NATIONAL DRUG INFORMATION CENTER

Telefax: (02) 5264384
Website: http://www.druginfo.ph
Email Address: ndic@druginfo.ph

Page | 554
NATIONAL POISON MANAGEMENT AND CONTROL CENTER

LUZON
Philippine General Hospital
Phone Number: (02) 5241078, Fax: (02) 5260062, SUN: 09228961541;
GLOBE: 09667189904
Email Address: uppoisoncenter@gmail.com

East Avenue Medical Center

Phone Number: (02) 89211212; (02) 434-2511
Email Address: eamctox@gmail.com

Rizal Medical Center

Contact Number: 0966 178 3773
Email Address: rizalmedpoisoncontrol@gmail.com

Batangas Regional Hospital

Phone Number: (043) 723-3578

VISAYAS
Eastern Visayas Regional Medical Center
Phone Number: (053) 3213131, (053) 3213129 (F)

MINDANAO
Zamboanga Medical Center
Phone Number: (062) 9912934, (062) 9910537

PHILIPPINE HEALTH INSURANCE CORPORATION

Trunkline: (02) 84417444
Call center: (02) 84417442
Website: http://www.philhealth.gov.ph
Email Address: actioncenter@philhealth.gov.ph

PHILIPPINE INSTITUTE OF TRADITIONAL AND ALTERNATIVE HEALTH CARE

(PITAHC)
Phone Number: (02) 8376-3067 / 8376-3068; (02) 8282-5193 / 8282-5194
Website: https://pitahc.gov.ph/
Email Address: pitahc@gmail.com

Page | 555
 REFERENCES
Administrative Order No. 163 s. 2002. “Implementing Guidelines and Procedures
in the Procurement and Requisition of Drugs and Medicines by the
Department of Health pursuant to Executive Order No. 49.”

Administrative Order No. 2014-0009. “Implementing Guidelines on the Rational

Use of Medicines (RUM) Pillar of the Philippine Medicines Policy.”

Administrative Order No. 2016-0034. “The New Implementing Guidelines of the

Philippine National Formulary System.”

American College of Cardiology and American Heart Association Task Force on

Clinical Practice Guidelines. 2017 Guidelines for the Prevention, Detection,
Evaluation and Management of High Blood Pressure in Adults. J Am C

American Association of Clinical Endocrinologists (AACE), 2007.

American College of Physicians (ACP), 2007.

American Diabetes Association Standards of Medical Care (ACE), 2010 and

updates as of 2013.

Bravo, LC, Gatchalian, SR, Gonzales, MLM, et. al., 2011, Handbook of Pediatric
Infectious Disease, 5th Edition. UP College of Medicine-Philippine General
Hospital.

BMJ Group and the Royal Pharmaceutical Society of Great Britain, September
2013 – March 2014, British National Formulary, 66th edition, London: BMJ
Group and Pharmaceutical Press.

BMJ Group, the Royal Pharmaceutical Society of Great Britain, and RCPCH
Publications Ltd., July 2013 – July 2014, British National Formulary for
Children, London: BMJ Group, Pharmaceutical Press and RCPCH
Publications Ltd.

Bureau of Food and Drugs. Philippine Phamacopoeia 1 (PP 1). 1st Ed., Alabang,
Muntinlupa: Department of Health-Bureau of Food and Drugs, 2004.

Bush, L. Staphylococal infections. MSD Manual. June 2019. Available from:

https://www.msdmanuals.com/professional/infectious-diseases/gram-
positive-cocci/staphylococcal-infections?query=impetigo. Accessed on:
21 Feb 2020

Canadian Diabetes Association (CDA), 2008.

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Antimicrobial Resistance Surveillance Program Annual Report – 2018. Manila:
Department of Health - Antimicrobial Resistance Surveillance Program,
2019.

Antimicrobial Resistance Surveillance Program Annual Report – 2019. Manila:

Department of Health - Antimicrobial Resistance Surveillance Program,
2020.

Centers for Disease Control and Prevention. (2013). Methicillin-resistant

Staphylococcus aureus (MRSA) infections. Retrieved from
http://cdc.gov/mrsa/.

Cunfliffe T. Blistering (bullous) disorders. Primary Care Dermatology Society.

Available from: http://www.pcds.org.uk/clinical-guidance/bullous-
disorders-an-overview#!prettyPhoto. Accessed on: 21 Feb 2020.

Collaborative Statement of the Philippine Society for Microbiology and Infectious

Diseases, and Philippine Foundation for Vaccination, 2012, Handbook on
Adult Immunization for Filipinos 2012 Update, 2nd edition, Makati City,
Philippines: Zurbano Publishing & Printing Corp.

Consultative meetings with representatives from the PSEDM and Diabetes

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 INDEX
A
Aciclovir / Acyclovir 203
Activated Charcoal, USP 329
Akapulko 544
Albendazole 303
Aluminum Hydroxide + Magnesium Hydroxide 10
Amlodipine 92
Amoxicillin 13, 150
Ampicillin 152
Anti-rabies Serum 206
Anti-tetanus Serum 207
Artemether + Lumefantrine 296
Ascorbic Acid (Vitamin C) 35
Aspirin 49, 109, 234
Atenolol 91
Atorvastatin 103
Atropine 14, 234
Azithromycin 177
B
Balanced Multiple Maintenance Solution 59
Balanced Multiple Replacement Solution 60
BCG Vaccine 212
Biperiden 256
Bisacodyl 20
Butamirate 316
C
Calamine 112
Calcium Carbonate 39
Calcium Gluconate 41, 62
Calcium Carbonate + Vitamin D3 42
Captopril 80
Carbamazepine 249, 262, 283
Cefalexin 166
Cefixime 167
Ceftriaxone 169
Cefuroxime 173
Celecoxib 235
Cetirizine 316
Chloramphenicol 146
Chloroquine 298
Chlorpromazine 264
Ciprofloxacin 187
Clarithromycin 13, 179
Clindamycin 183
Page | 566
Clofazimine 200
Clonidine 97
Clopidogrel 50, 110
Clotrimazole 111, 193, 325
Cloxacillin 160
Clozapine 266
Co-Amoxiclav (Amoxicillin + Potassium Clavulanate) 163
Cobra Antivenin 207
Common Poisoning, (CPG) 490
Cotrimoxazole (Trimethoprim + Sulfamethoxazole) 175
D
Dapsone 201
Dexamethasone 130
Dextrose (see Glucose) 63
Diabetes Mellitus, (CPG) 25
Diarrhea, (CPG) 421
Diazepam 253, 282
Dicycloverine 16
Diethylcarbamazine 304
Digoxin 70
Diltiazem 96
Diphenhydramine 260, 318
Diphtheria-Tetanus Toxoid and Pertussis Vaccine 213
Dopamine 71
Doxycycline 147, 301
E
Enalapril 82
Enalapril + Hydrochlorothiazide 83
Epinephrine 73, 307
Erythromycin 181, 323
Escitalopram 288
Ethambutol 194
Ethinylestradiol + Levonorgestrel 124
Ethyl Alcohol 118, 330
F
Fenofibrate 108
Ferrous Salt 43, 54
Ferrous Salt + Folic Acid 44, 55
Finasteride 127
Fluoxetine 289
Fluphenazine 270
Fluticasone + Salmeterol 308
Folic Acid 36, 55
Furosemide 101
Fusidic Acid 113
Page | 567
G
Gabapentin 262
Gentamicin 185
Gliclazide 31
Glucose (50%) Solution 63
Glucose (Dextrose, 5%) in Lactated Ringer’s 57
Glucose (Dextrose, 5%) in 0.3% Sodium Chloride 56
Glucose (Dextrose, 5%) in 0.9% Sodium Chloride 56
Glucose (Dextrose, 5%) in Water 62
H
Haemophilus influenzae Type B Conjugate Vaccine (Hib) 215
Haloperidol 272
Hepatitis B Vaccine (Recombinant DNA) 216
Hydralazine 78
Hydrochlorothiazide 100
Hydrocortisone 116, 131, 320
Hydrogen Peroxide 119
Hyoscine 17
Hypertension in Adults, (CPG) 434
I
Ibuprofen 238, 245
Influenza Polyvalent Vaccine 217
Insulin
Biphasic Isophane Human Insulin (70/30) 27
Regular Insulin (Recombinant DNA, Human) 29
NPH/Isophane Insulin Human 28
Ipratropium 310
Ipratropium + Salbutamol 311
Isoniazid 195
Isoniazid + Rifampicin 199
Isoniazid + Rifampicin + Ethambutol 199
Isoniazid + Rifampicin + Pyrazinamide + Ethambutol 200
Isosorbide Dinitrate 75
Isosorbide 5 Mononitrate 76

K
Ketoconazole 111

L
Lactated Ringer’s Solution (Ringer’s Lactate) 65
Lactulose 21
Lagundi 322
Levodopa + Carbidopa 258
Levothyroxine 138
Lidocaine, Gel 260, 327
Page | 568
 Inj. 260
Lithium Carbonate 275
Live Attenuated Measles Vaccine 219
Live Attenuated Measles, Mumps and Rubella Vaccine 220
Live Attenuated Bivalent Oral Polio Vaccine 225
Loperamide 24
Loratadine 319
Losartan 85
Losartan + Hydrochlorothiazide 86
M
Magnesium Sulfate 66, 120, 255
Mebendazole 304
Medroxyprogesterone 125
Mefenamic Acid 239
Meningococcal Polysaccharide vaccine 222
Metformin 29
Methicillin-resistant Staphylococcus aureus (MRSA) 183
Methimazole 141
Methyldopa 99
Methylprednisolone 133
Metoclopramide 18
Metoprolol 90
Metronidazole 14, 190, 295
Micronutrient Powder 48
Montelukast 313
Multivitamins for Infants, Children and Adults 32
Mupirocin 113
N
Naproxen 241
Neomycin + Polymyxin B + Fluocinolone Acetonide 325
Nicardipine 93
Nitrofuranton 191
NPH/Isophane Insulin Human 28
O
Ofloxacin 326
Olanzapine 277
Omeprazole 11
Oral Rehydration Salts 22
In management of dehydration in infants and children
Oseltamivir 204
Oxytocin 137

P
Paracetamol 247

Page | 569
Penicillin G Benzathine (Benzathine benzylpenicillin) 154
Penicillin G Crystalline (Benzylpenicillin) 157
Permethrin 305
Phenoxymethylpenicillin (Penicillin V) 158
Phytomenadione 37, 333
Pneumonia, Community-Acquired, (CPG)
In immunocompetent adults 340
Pediatric CAP 351
Poliomyelitis Vaccine (Types 1,2,3) Inactivated
Potassium Chloride 46
Povidone-Iodine 117, 307
Praziquantel 302
Prednisone 135
Primaquine 300
Pyrazinamide 196

R
Rabies Immunoglobulin,
Human (HRIG) 209
Rabies Vaccine Vero Cell (Purified) 227
Regular Insulin (Recombinant DNA, Human) 29
Retinol (Vitamin A) 33
Rifampicin 197, 202
Risperidone 279
Rosuvastatin, 105

S
Salbutamol 314
Sambong 533
Sertraline 291
Silver Sulfadiazine 114
Simvastatin 106
Sodium Chloride (0.9%) 61
Sodium Chloride 67
Sterile Water for Injection 68
T
Tamsulosin 127
Tetanus Immunoglobulin 211
Tetanus Toxoid 229
Tobramycin 323
Tobramycin + Dexamethasone 324
Tramadol 244
Tranexamic Acid 52
Trimethoprim + Sulfamethoxazole (See cotrimoxazole)
Typhoid Vaccine

Page | 570
U
Urinary Tract Infection, (CPG) 365
V
Valproic Acid (See Valproate)
Valproate 251, 285
Vitamin B1 B6 B12 38
Z
Zinc 47

Page | 571