TERTIARY RESOURCES

PPB 485: Drug Literature Evaluation

Fall 2022

Objectives
• Define tertiary drug information (DI) resources
• Identify advantages and disadvantages of tertiary resources
• Classify tertiary resources
• Critically evaluate tertiary resources
• Describe the type of information found in the most common tertiary resources
• Identify electronic books, MCPHS databases, product labeling resources, and
specialty resources that may be useful for accessing information to answer DI
questions

Where do you look?

• A resident asks you want to find information about the use of aspirin for
Kawasaki’s Disease.

• First, you would like to (should) learn more about Kawasaki’s Disease.

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 Example Question
Which of the following resources may have information about the signs
and symptoms of Kawasaki’s Disease? Choose all that apply

A. Micromedex
B. Harrison’s
C. Brigg’s
D. Trissel’s

Example Question
Which of the following resources may have information about the off-label
use of nifedipine for pre-term labor? Choose all that apply

A. Nifedipine product information

B. Clinical Pharmacology
C. Lexicomp Online
D. PDR

Example Question
Which one of the following resources may have information about
therapeutic interchange of nifedipine products?

A. Purple Book
B. Pink Book
C. Orange Book
D. Yellow Book

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 Definitions
• Primary Literature
• Original information or research
• Secondary Literature or Resources
• Reviews of original research (analyzes,
interprets, evaluates -“adds value” to original
research – e.g. Systematic Review)
• OR bibliographic, indexing databases
• Suggestions for use
• Tertiary: determine general answer to a DI
question
• Secondary databases: identify primary or
secondary literature to answer specific DI question
• Primary: determine specific clinical
recommendation for a patient

• Tertiary Literature
• Information summarized or condensed with
references to primary and secondary literature
- a convenient summary or overview of a
topic.

Tertiary Resources and Databases

• Where you find overviews or summaries about a subject
• Can be the first step in searching for an answer to a DI question
• Resources include:
• Textbooks/handbooks
• Review articles
• Computerized information databases (e.g. Micromedex, Clinical Pharmacology)
• Prescribing Information or “package inserts”
• Drug information software for electronic devices (e.g. Apps for smartphones)
• Summary information from websites

Advantages Disadvantages
• Easy to access • Information may not be current
• Most pharmacies have some print or • Information may not be complete
electronic tertiary references • Handbooks or apps particularly
• Easy to use limited
• No special training required • Information may be biased
• Presented only through perspective of
author/editor – expert opinion

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 Evaluating Tertiary Resources
• Is the information current?
Accuracy Appropriateness • Will it cover the information I am
looking for?
• Are the authors qualified?
• How much detail is provided?
Authority Completeness • How reputable are the sources of
information?

References

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Evaluating a website – Is it CRAP?

• Is the website up to date?
• Balanced and unbiased? Does it
include references?
• Who is the creator? Credentials?
Reputable?
• Is the information to teach or to sell?
Fact or opinion?

The C.R.A.P. Test was created by librarian Molly Beestrum at Dominican University

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How Are References Cited?

• Within text:
• Identified by superscript, sequential numbers ( 1) or (author, date) with complete citation at
the end of paper
• End of resource
• Sequentially numbered or alphabetical

• Citation Style for this course is American Medical Association (AMA) format
• Intext, sequential numbers
• Reference retains number once used
• Citation style Lib Guide https://mcphs.libguides.com/citation

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 Common Citation Styles
American Medical Association (AMA) format example*
Proton pump inhibitors are first-line agents amongst gastroenterologists for
peptic ulcer disease.1
1. Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A
Comprehensive Review. Gut Liver. 2017;11(1):27-37. doi:10.5009/gnl15502
American Psychological Association (APA) format example
The majority of Americans experience stress in their daily lives (American
Psychological Association, 2017).
American Psychological Association. (2017). Stress in America: The state of our
nation. https://www.apa.org/news/press/releases/stress/2017/state-nation.pdf

*Recommended citation style for this course

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Print versus eTextbooks

• Electronic version of a textbook may differ from the print
• More frequently updated
• May include references that the textbook version does not
• Advantages of eTextbooks
• Remote access/convenience, can search quickly across multiple sections
• Can include special features (e.g., links, dictionaries)
• Disadvantages of eTextbooks
• Cannot quickly scan pages for information
• $$$Cost

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Computerized versus Mobile Databases (Apps)

• Mobile version is usually less comprehensive than original database
• Mobile database is useful in patient care setting (point of care) as a quick
resource
• Should follow-up with more comprehensive resource when necessary

Mobile Apps
MCPHS Lib Guide https://mcphs.libguides.com/mobile

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 Important
• No single drug information resource covers every topic
• If available, the references cited in resource should be checked to see what is
the source of information provided and how current it is

• Multiple resources should be used to verify information if possible

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General Classification of Tertiary Resources

• Disease state oriented
• Drug therapy oriented
• Specialty references
• IV therapy, drug interactions, pregnancy, geriatrics, pediatrics, etc.

• A mix of all - Some databases (e.g., Micromedex) include all of the above types
of information

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Tertiary Resources
• Database Libraries of E-Texts • Drug Databases
• Stat!Ref • Clinical Pharmacology
• AccessPharmacy • Lexicomp
• AccessMedicine • Micromedex
• Pharmacy Library

• Product Information • FDA Websites

• Specialty Resources

MCPHS Library – access at https://my.mcphs.edu/login

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 Stat!Ref
• Contains a wide variety of electronic textbooks that can be searched
simultaneously
• Subscribers pay only for the titles they want to receive
• Available through MCPHS
• 7 simultaneous users
• MCPHS version includes AHFS and ASHP Injectable Drug Information
• Also available through MAHSLIN (Massachusetts Health Sciences
Library Network)
• Shared use with other institutions
• Use if MCPHS not available (on Library website)
• May not have all MCPHS selections however

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AccessPharmacy
• Texts related to pharmacy education including:
• Applied Clinical Pharmacokinetics
• Basic and Clinical Pharmacology
• Goodman & Gilman
• Pharmacy and Federal Drug Law Review
• Pharmacotherapy: A Pathophysiologic Approach
• Harrison’s Principles of Internal Medicine Online
• NAPLEX Review Guide
• Study tools- Top 300 Rx drugs, Top 100 non-Rx drugs
• Ability to select a specific text or search all texts available

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 AccessMedicine
• Some texts overlap with Access Pharmacy
• Medical texts related to general internal medicine as well as specific topics:
• Cardiovascular disease
• Neurology
• Emergency medicine
• Obstetrics /Gynecology
• Psychiatry
• Pediatrics
• Geriatrics
• Quick reference, flashcards

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Pharmacy Library
• PharmacyLibrary features APhA's textbooks, learning exercises
• Handbook of Nonprescription Drugs
• The APhA Complete Review for Pharmacy Math
• The APhA Complete Review for Pharmacy (NAPLEX® Review)
• Communication Skills for Pharmacists
• Complete Math Review for Pharmacy
• Handbook of Basic Pharmacokinetics
• Handbook of Nonprescription Drugs Quick Reference
• Immunization Handbook for Pharmacists, 5th Edition (Angelo)
• Peripheral Brain for the Pharmacist
• The Pharmacist in Public Health (Truong, Bresette, & Sellers)
• The Pharmacy Professional’s Guide to Résumés, CVs, & Interviewing

APhA = The American Pharmacists Association

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General Pharmacotherapy Textbooks

• Most provide similar information including:
• Pharmacology, indications (including off-label), side effects, drug interactions,
dosing, federal control schedule, dosage forms, etc.
• Key major difference is in level of detail
• Example: AHFS DI may have information about the less common off-label uses
• Handbooks have very limited detail
• Not all texts are referenced
• E-versions of texts may be referenced but not print version (e.g., AHFS)
• Not all are up to date
• Check for publication date, text version

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 Prescribing Information (PI) / Drug Product Label
FDA approved labeling (indication) follows a standard format
Boxed Warning (if applicable)
1. Indications and Usage
2. Dosage and Administration
3. Dosage Forms and Strengths
4. Contraindications
5. Warnings and Precautions
6. Adverse Reactions
7. Drug Interactions
8. Use in Specific Populations
“Package Insert”
9. Drug Abuse and Dependence
10 Over-dosage
11. Description (e.g., dosage forms, ingredients)
12. Clinical Pharmacology
13. Nonclinical Toxicology
14. Clinical Studies
15 References
16. How Supplied/Storage and Handling
17. Patient Counseling

FDA provides PI at http://labels.fda.gov for access to the most recent information

National Library of Medicine link to PI: http://dailymed.nlm.nih.gov/dailymed/about.cfm
• Check to see date of last update

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A Boxed Warning
Prozac Boxed Warning appears first or at the top
of the labeling if one is
required by the FDA

Warning has a black border which draws attention to the Adverse Drug Reaction

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Off-Label Drug Use

• The FDA does not restrict how a drug can be used, but limits manufacturer’s
communication and marketing to what is FDA approved
• It is not unusual for a drug to be prescribed for a different use (or dose, route,
etc.)
• A survey of office-based physicians reported that 31 percent of all antidepressants, anticonvulsants,
and antipsychotic medications prescribed were for off-label indications…. in community clinical
practices, 40 to 80 percent of recipients of commonly prescribed psychotropic medications (including
antidepressants, antipsychotics, and anticonvulsants) were receiving these medications for off-label
indications
• Utilizing resources that cover off-label use is important

Syed SA, Dixson BA, Constantino E, Regan J. The Law and Practice of Off-Label Prescribing and Physician Promotion. J Am Acad
Psychiatry Law. 2021;49(1):53-59. doi:10.29158/JAAPL.200049-20

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 Where Does Information in Product Labeling Come From?
• Information is generally based on data from clinical trials conducted prior to
marketing
• May be limited especially in terms of adverse drug reaction (ADR) information
and use in special populations (e.g., children, elderly, patients with serious
disabilities)
• Can be revised after marketing but it may take some time to do so
• Example: A Boxed Warning or “Black Box warning” can be added which notes
serious ADR associated with drug

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Tertiary Drug Databases

• Micromedex, Clinical Pharmacology, Lexicomp Online

• General Drug Information

• Indications and Usage • Overdosage

• Dosage and Administration • Description
• Dosage Forms and Strengths • Clinical Pharmacology
• Contraindications • Nonclinical Toxicology
• Warnings and Precautions • Clinical Studies
• Adverse Reactions • References
• Drug Interactions • How Supplied/Storage and Handling
• Use in Specific Populations (sections include • Patient Counseling Information
Pregnancy, Nursing, Geriatric, Renal, Hepatic)

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Micromedex
• Very comprehensive and expensive
• Includes
• Disease state, toxicology, and natural product information
• Martindale: The Complete Drug Reference –foreign product names (non-US)
• Index Nominum –foreign product names (non-US)
• Red Book - drug cost information
• Summary information (Quick Answers) presented first
• Should always go to “In-Depth Answers” for details before answering question

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 Lexicomp Online
• Comprehensive but less detail than Micromedex
• Limited disease information
• Includes
• AHFS Clinical Drug Information
• AHFS Essentials provides less detail
• “Briggs” Drugs in Pregnancy & Lactation
• Lab test and Pharmacogenomic information
Natural products
•
Foreign product names
•
• Pronunciation feature which may be useful

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Clinical Pharmacology
• Less comprehensive than Micromedex
• Limited disease state information
• Includes
• Information on product availability, including discontinued products
• Natural Products (limited)
• Foreign product names
• Includes information on common natural products
• Beers list (potentially inappropriate medications in older adults)

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Additional Drug Information Resources

• Goodman and Gilman’s The Pharmacological Basis of Therapeutics (print and e-book,
Access Pharmacy)
• Pharmacology, drug structure, physiology, pathophysiology
• AHFS Drug Information (print and e-book, Lexicomp and STAT Ref)
• Organized by drug class, very comprehensive, focus is on Rx drugs
• Includes off-label uses of drugs and biologicals, and therapeutic guidelines
• Prescriber’s Digital Reference (PDR) freely available at http://www.pdr.net/
• Official product labeling information (“package inserts”)
• No off-label use

• More are availabe

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 Specialty Tertiary Resources
• For information on specific patient populations (e.g., geriatrics, pediatrics)
• For information regarding a specific practice area (e.g., infectious diseases,
cardiology)
• For information on a specific aspect of drug therapy (e.g., ADRs, parenteral
drug therapy, drug interactions, purchasing information, product identification,
drugs in pregnancy, extemporaneous compounding)
• For information about herbs and natural products

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Drug Dosing in Special Populations Common Resources

• Pediatrics: Harriet Lane Handbook (ebook), American Academy of Pediatrics
(AAP) Red Book (infectious disease), Neofax (in Micromedex), Lexicomp
Pediatric & Neonatal Dosage Handbook
• Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal
Risk, may be referred to as “Briggs” (e-book and Lexicomp)
• Drug Prescribing in Renal Failure, may be referred to as “Aronoff’s” (e-book)
• Lexicomp Geriatric Dosage Handbook
• The Sanford Guide to Antimicrobial Therapy

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FDA Orange Book

• Approved Drug Products with Therapeutic Equivalence Evaluation
• Available on FDA website https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
• Provides information on AB ratings
• If there are no bioequivalence problems, generic is designated AA, AN, AO, AP, or AT,
depending on the dosage form (AA = standard, AN = nebulized, AO= injectable oil, AP=
injectable aqueous, AT= topical) and generic is interchangeable
• AB = If actual or potential bioequivalence problems have been resolved with adequate in
vivo and/or in vitro evidence supporting bioequivalence, also interchangeable
• B rated drug products are those that that FDA considers NOT to be therapeutically
equivalent to other pharmaceutically equivalent products and are not interchangeable
• Orange Book codes listed in Redbook (Micromedex), Clinical Pharmacology
and Facts & Comparisons

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 AA No bioequivalence problems, considered therapeutically equivalent
Code AB
AB1
Meets necessary bioequivalence requirements
Meets bioequivalence requirements to AB1 rated reference drug
Interpretation AB2 Meets bioequivalence requirements to AB2 rated reference drug
AB3 Meets bioequivalence requirements to AB3 rated reference drug
AB4 Meets bioequivalence requirements to AB4 rated reference drug
AN Solution or powder for aerosolization
AO Injectable oil solutions
AP Injectable aqueous solutions
AT Topical Products
B Requires further FDA investigation, NOT therapeutically equivalent
BC Controlled-release tablet, capsule, or injectable
BD Documented bioequivalence problems
BE Enteric coated oral dosage forms
BN Product in aerosol-nebulizer delivery system
BP Potential bioequivalence problems
BR Suppository or enema for systemic use
BS Testing standards are insufficient for determination
BT Topical products with bioequivalence issues
BX Insufficient data to confirm bioequivalence
EE Evaluated by the FDA, but a rating is not available for this labeler’s product
ZZ ZZ FDA standard with no orange book code

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Are these products interchangeable?

FDA Orange Book

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FDA Purple Book

• Released in 2015
• Similar to Orange Book but is for biological products
• Lists biologic products, including biosimilar and interchangeable products
• https://purplebooksearch.fda.gov/

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 FDA Purple Book
• Search by Drug

An interchangeable product meets the
requirements for a biosimilar product and
is can be substituted for the reference
product without the intervention of the
prescribing health care provider.
A biosimilar product is a biological product that is highly
similar to and has no clinically meaningful differences in terms
of safety or effectiveness from an existing FDA-licensed
(approved) reference product.

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FDA Biosimilars
• Over 30approved biosimilars, 2 FDA approved interchangeables in 2021

tion
forma
duct-in
similar-pro
rs/bio
simila
gs/bio
da.gov/dru
.f
/www
https:/

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The Pink Book

• Published by CDC
• Provides update on vaccine-preventable
diseases
• Chapters have information about disease,
epidemiology, trends in the US, clinical
features, diagnosis, management, vaccine
schedule, vaccine ADRs, vaccine storage
and handling
• Available on CDC web site
http://www.cdc.gov/vaccines/pubs/pinkboo
k/index.html

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 The Yellow Book
• Published every 2 years by CDC
• Information on international travel for
health professionals
• Includes how to plan for trips, risks
associated with travel to specific
countries, information on specific diseases
related to travel and counseling/advice
• Available on CDC web site
https://wwwnc.cdc.gov/travel/page/yellow
book-home-2020

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Adverse Drug Reaction References (ADRs)

• Information on general ADRs can be found in the general drug therapy
tertiary resources (e.g. AHFS, drug databases such as Micromedex)
• May need to go to primary literature or reputable internet site (fda and
other alerts) for the most current information about ADRs, especially for
new drugs
• www.fdable.com can search FDA medwatch database
• LiverTox – information on Drug-induced liver disease
https://www.ncbi.nlm.nih.gov/books/NBK547852/
• TOXNET–toxicology and hazardous chemicals
https://www.nlm.nih.gov/toxnet/index.html

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Drug Interaction References

• Most general drug resources will include a section on drug interactions
• Drug databases include drug interaction, drug-drug interaction (DDI)
checker

• Specialized DDI references can provide more detail, clinical significance

and management of drug-drug interactions
• Stockley’s Drug Interactions – in print at MCPHS, electronic not
subscribed

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 Pregnancy and Lactation References
• Often limited information on this subject
• Required as part of manufacturer’s information, generally based on animal data

• Ethical issues prevent evaluation of teratogenicity through controlled clinical

trials

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Previous FDA Pregnancy Category Ratings

• A- controlled trials in humans show no risk
• e.g., doxylamine, folic acid, levothyroxine
• B- human studies no risk/ animal studies risk or animal studies no risk / limited
human studies
• e.g., amoxicillin, loratadine, ondansetron These ratings are overly
simplistic, can be
• C- no data or evidence of risk in animals misinterpreted and most
have been replaced
• e.g., fluconazole, metoprolol, sertraline
• D- evidence of risk in humans but benefit may outweigh risk
• e.g., lithium, lisinopril, phenytoin,
• X- evidence of risk or no utility of drug in pregnancy
• e.g., methotrexate, simvastatin, warfarin

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“New” FDA Required Labeling

• Risk for both pregnancy and lactation and effects on female and male
reproductive potential
• Fetal risk summary begins with a one sentence risk conclusion about 4
types of developmental abnormalities:
• Structural abnormalities (malformations etc.)
• Fetal and infant mortality (miscarriage, stillbirth)
• Impaired physiologic function (e.g., deafness, neurodevelopmental effects)
• Alterations to growth (includes restriction, excess, delayed maturation)

• Indicates if risk conclusion is based on animal or human data

• If based on humans, there is a description about the most important data concerning
effects on fetus

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 Pregnancy and Lactation References
• Drugs in Pregnancy and Lactation
• AKA “Briggs”
• Gold standard reference on this topic
• Organized in drug monograph format
• Summarizes both human and animal literature and makes
recommendation regarding fetal risk and breast feeding
• Recommendation may differ from manufacturer in some cases
• Well referenced and comes with supplements
• Available electronically through Lexicomp & E-books at MCPHS

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Click on link to read the

meaning of the rating

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Pregnancy and Lactation References

• LactMed
• Part of the National Library of Medicine
TOXNET system
• Includes information on the levels of
substances in breast milk and infant blood
• Possible adverse effects in the nursing infant
• Suggested therapeutic alternatives to those
drugs are provided, where appropriate

• Location - NCBI bookshelf

• https://www.ncbi.nlm.nih.gov/books/NBK5019
22/

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 Parenteral Compatibility References
• ASHP Injectable Drug Information
• AKA “Trissel’s” – previous author (40+yrs)
• previous title Handbook on Injectable Drugs
• Very comprehensive reference
• Organized in drug monograph format by generic name
• Includes the chemical properties of the drug, stability and IV dosing information
• Includes solution compatibility, additive compatibility, syringe compatibility and Y-
site compatibility
• Available electronically in E-books (Stat!Ref)
• Source used by Clinical Pharmacology, Micromedex, and Lexicomp

Solution, IV bag, Y-site, syringe

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of Ampicillin

53

of Ampicillin

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 Metronidazole - AHFS 8:30.92

Stability — Intact containers of metronidazole injection should be

stored at controlled room temperature and protected from light until
time of use.(3798) (3799) The injection should not be
refrigerated.(3798) (3799) Freezing also should be avoided.(3799)

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Parenteral Compatibility References

• King Guide to Parenteral Admixtures
• Less comprehensive than “Trissel’s”
• Online or in print
• No longer available at MCPHS

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 References for Compounding
• Merck Index
• Chemical properties of drug (e.g., molecular weight, solubility, melting point)
• Do not confuse with Merck Manual
• MCPHS library in print
• Remington: The Science and Practice of Pharmacy
• In addition to a variety of pharmacy related topics, has information about pharmaceutics, medicinal
chemistry and compounding techniques and ingredients
• MCPHS library in print
• The United States Pharmacopeia and The National Formulary (USP–NF)
• A combination of 2 resources, available through e-databases
• Contains the pharmacopeial standards for medicines, dosage forms, drug substances, excipients,
medical devices, and dietary supplements
• Compounding information also available from all 3 drug databases (limited)

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International/ Foreign Product References

• Martindale: the Complete Drug Reference

• Produced in UK
• Could be considered a general drug reference (e.g., has
information on uses, dosing, drug interactions etc.)
• Organized by therapeutic use
• Includes some information about herbal therapies
• Covers 40+ countries
• Available in Micromedex

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International/ Foreign Products References

• Index Nominum
• Domestic and foreign products listed by generic and
trade names
• Each generic entry includes international trade names,
manufacturer and a therapeutic use category
• List of country abbreviations

• Does not describe pharmacology, dosing or ADRs

• Not as detailed as Martindale
• Available in Micromedex

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 Note: In Micromedex the links to
Martindale and Index Nominum
appears after entering initial search
term

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Brand and Country names

Index Nominum Martindale

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Natural Products References

• Area where the interest is growing and there is a need for more comprehensive
information, especially for drug interactions and side effects
• Look for texts that are written by specialist in field, referenced and non-biased
• Micromedex, Clinical Pharmacology, & Lexicomp have some information

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 Natural Product References
• Handbook of Nonprescription Drugs
• Comprehensive text for OTC products
• Organized by disease state
• Includes information on natural products, dietary supplements
and complimentary medicine
• Available as ebook or Pharmacy Library Database
• Interactions Guide
• Available on the library databases
• Interactions between pharmaceutical drugs and “natural” products
such as nutrients and herbs

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Natural Products References

• National Center for Complementary and Integrative Health (NCCIH)
• Government agency of the National Institutes of Health (NIH) within the U.S.
Department of Health and Human Services.
• Provides usefulness, and safety of complementary and integrative health
approaches
• Brief fact sheets about common supplements, not comprehensive
• https://www.nccih.nih.gov/

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Natural Products References

• Natural Medicines Database - most comprehensive
• Very well referenced, unbiased, evidence-based, peer reviewed
• Has checkers for interactions, effectiveness use in pregnancy and lactation
• Professional monographs, patient handouts, commercial products

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 Evidence Based Medicine Database
• Cochrane Library
• Cochrane Database of Systematic Reviews (CDSR)
• Considered the gold-standard of systematic reviews: highly structured,
methodological research

More to come on this database

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Evidence Based Medicine Database (Disease info)

• DynaMed
• Evidence-based point-of-care clinical decision support system and reference
tool; peer reviewed, organized
• Defines and applies a level of evidence (LOE) to determine the quality of the
best available evidence
• Very good resource for Clinical Practice Guidelines
• Best for disease state management (therapeutics); risk factors, diagnosis,
treatment, prognosis
• DynaMed includes Micromedex for medication information (quick answer)
• For complete drug information go to Micromedex, or use Clinical
Pharmacology, Lexicomp Online

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How About the Web?

• Many reputable resources available
• Investigate, Evaluate
• Lexicomp has a link to clinical sites
• See handout for examples

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 MCPHS Library Research Guides
• https://mcphs.libguides.com/

• Links are posted on Blackboard left hand menu

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Summary
• Tertiary references provide a good overview of a topic and should be used first
when researching for information
• May be general or specific in nature
• No single resource will meet your practice needs
• More than one resource should be used to validate information found

• PRACTICE using the references to use them optimally

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