Gahart's 2021 Intravenous Medications:

A Handbook for Nurses and Health

Professionals - eBook PDF
Visit to download the full and correct content document:
https://ebooksecure.com/download/gaharts-2021-intravenous-medications-a-handboo
k-for-nurses-and-health-professionals-ebook-pdf/
YOU’VE JUST PURCHASED

MORE THAN
A TEXTBOOK!
Enhance your learning with Evolve Student Resources.
These online study tools and exercises can help deepen your
understanding of textbook content so you can be more
prepared for class, perform better on exams, and succeed
in your course.

Activate the complete learning experience that comes with each

NEW textbook purchase by registering with your scratch-off access code at

http://evolve.elsevier.com/IVMeds/
If you rented or purchased a used book and the scratch-off code at right
has already been revealed, the code may have been used and cannot
be re-used for registration. To purchase a new code to access these
valuable study resources, simply follow the link above.

Place
REGISTER TODAY! Sticker
Here

You can now purchase Elsevier products on Evolve!

Go to evolve.elsevier.com/shop
to search and browse for products.

2019v1.0
 General Dilution Chart (Gm to mg)
Amount of Diluent
Amount of Drug
Required in Grams 1,000 mL 500 mL 250 mL 125 mL 100 mL 50 mL 25 mL
mg/mL mg/mL mg/mL mg/mL mg/mL mg/mL mg/mL
20 Gm 20 40 80 160 200 400 800
19 Gm 19 38 76 152 190 380 760
18 Gm 18 36 72 144 180 360 720
17 Gm 17 34 68 136 170 340 680
16 Gm 16 32 64 128 160 320 640
15 Gm 15 30 60 120 150 300 600
14 Gm 14 28 56 112 140 280 560
13 Gm 13 26 52 104 130 260 520
12 Gm 12 24 48 96 120 240 480
11 Gm 11 22 44 88 110 220 440
10 Gm 10 20 40 80 100 200 400
9 Gm 9 18 36 72 90 180 360
8 Gm 8 16 32 64 80 160 320
7 Gm 7 14 28 56 70 140 280
6 Gm 6 12 24 48 60 120 240
5 Gm 5 10 20 40 50 100 200
4.5 Gm 4.5 9 18 36 45 90 180
4 Gm 4 8 16 32 40 80 160
3.5 Gm 3.5 7 14 28 35 70 140
3 Gm 3 6 12 24 30 60 120
2.5 Gm 2.5 5 10 20 25 50 100
2 Gm 2 4 8 16 20 40 80
1.5 Gm 1.5 3 6 12 15 30 60
1 Gm 1 2 4 8 10 20 40
0.5 Gm 0.5 1 2 4 5 10 20
0.25 Gm 0.25 0.5 1 2 2.5 5 10

To use chart:
1. Find mg/mL desired, track to amount of diluent desired and amount of drug in Grams
required.
2. Find amount of drug in Grams required, track to diluent desired and/or mg/mL
desired.
3. Find amount of diluent required, track to amount of drug in Grams and/or mg/mL
desired.
Formula: Substitute any number for X
X Grams diluted in 1,000 mL 5 X mg/mL (1 Gram in 1,000 mL 5 1 mg/mL)
X Grams diluted in 500 mL 5 2 X mg/mL (1 Gram in 500 mL 5 2 mg/mL)
X Grams diluted in 250 mL 5 4 X mg/mL (1 Gram in 250 mL 5 4 mg/mL)
X Grams diluted in 125 mL 5 8 X mg/mL (1 Gram in 125 ml 5 8 mg/mL)
X Grams diluted in 100 mL 5 10 X mg/mL (1 Gram in 100 mL 5 10 mg/mL)
X Grams diluted in 50 mL 5 20 X mg/mL (1 Gram in 50 mL 5 20 mg/mL)
X Grams diluted in 25 mL 5 40 X mg/mL (1 Gram in 25 mL 5 40 mg/mL)

Some variation occurs from manufacturer’s overfill or if the drug is in liquid form. If
absolute accuracy is required, these variations can be avoided by withdrawing an amount
in mL from the diluent equal to manufacturer’s overfill and/or an amount equal to the
amount in mL of the drug. Consult the pharmacist for specific information on manufac-
turer’s overfill of infusion fluids used in your facility. See next page.
 General Dilution Chart (mg to mcg)
Amount of Drug Amount of Diluent
Required in
Milligrams 1,000 mL 500 mL 250 mL 125 mL 100 mL 50 mL 25 mL
mcg/mL mcg/mL mcg/mL mcg/mL mcg/mL mcg/mL mcg/mL
20 mg 20 40 80 160 200 400 800
19 mg 19 38 76 152 190 380 760
18 mg 18 36 72 144 180 360 720
17 mg 17 34 68 136 170 340 680
16 mg 16 32 64 128 160 320 640
15 mg 15 30 60 120 150 300 600
14 mg 14 28 56 112 140 280 560
13 mg 13 26 52 104 130 260 520
12 mg 12 24 48 96 120 240 480
11 mg 11 22 44 88 110 220 440
10 mg 10 20 40 80 100 200 400
9 mg 9 18 36 72 90 180 360
8 mg 8 16 32 64 80 160 320
7 mg 7 14 28 56 70 140 280
6 mg 6 12 24 48 60 120 240
5 mg 5 10 20 40 50 100 200
4.5 mg 4.5 9 18 36 45 90 180
4 mg 4 8 16 32 40 80 160
3.5 mg 3.5 7 14 28 35 70 140
3 mg 3 6 12 24 30 60 120
2.5 mg 2.5 5 10 20 25 50 100
2 mg 2 4 8 16 20 40 80
1.5 mg 1.5 3 6 12 15 30 60
1 mg 1 2 4 8 10 20 40
0.5 mg 0.5 1 2 4 5 10 20
0.25 mg 0.25 0.5 1 2 2.5 5 10

To use chart:
1. Find mcg/mL desired, track to amount of diluent desired and amount of drug in mg
required.
2. Find amount of drug in mg required, track to diluent desired and/or mcg/mL desired.
3. Find amount of diluent required, track to amount of drug in mg and/or mcg/mL desired.
Formula: Substitute any number for X
X mg diluted in 1,000 mL 5 X mcg/mL (1 mg in 1,000 mL 5 1 mcg/mL)
X mg diluted in 500 mL 5 2 X mcg/mL (1 mg in 500 mL 5 2 mcg/mL)
X mg diluted in 250 mL 5 4 X mcg/mL (1 mg in 250 mL 5 4 mcg/mL)
X mg diluted in 125 mL 5 8 X mcg/mL (1 mg in 125 ml 5 8 mcg/mL)
X mg diluted in 100 mL 5 10 X mcg/mL (1 mg in 100 mL 5 10 mcg/mL)
X mg diluted in 50 mL 5 20 X mcg/mL (1 mg in 50 mL 5 20 mcg/mL)
X mg diluted in 25 mL 5 40 X mcg/mL (1 mg in 25 mL 5 40 mcg/mL)

Some variation occurs from manufacturer’s overfill or if the drug is in liquid form. If
absolute accuracy is required, these variations can be avoided by withdrawing an amount
in mL from the diluent equal to manufacturer’s overfill and/or an amount equal to the
amount in mL of the drug. Consult the pharmacist for specific information on manufac-
turer’s overfill of infusion fluids used in your facility.
 HOW TO USE THIS BOOK
STEP 1
Refer to the index at the back of the book. You can find any drug by any name in less than
5 seconds. All drugs are cross-indexed by generic and all known trade names. The index
is easily distinguished by a printed blue bar at the edge of the pages. Drugs are also in-
dexed by pharmacologic action. With one turn of the page, all drugs included in the text
with similar pharmacologic actions and their page numbers are available to you. Every-
thing is strictly alphabetized; you will never be required to refer to additional pages to
locate a drug.

STEP 2
Turn to the single page number given after the name of the drug. All information about
the drug is included as continuous reading. You will rarely be required to turn to another
section of the book to be completely informed. Specific breakdowns of each drug (Usual
Dose, Pediatric Dose, Dose Adjustments, Dilution, Compatibility, Rate of Administra-
tion, Actions, Indications and Uses, Precautions, Contraindications, Drug/Lab Interac-
tions, Side Effects, and Antidote) are consistent in format and printed in boldface type.
Subheadings under these categories are in boldface. Scan quickly for a Usual Dose
check, Dose Adjustment, Drug/Lab Interaction, Side Effect, or Antidote or carefully read
all included information. The choice is yours. A quick scan will take 5 to 10 seconds.
Even the most complicated drugs will take less than 2 minutes to read completely. Read
each monograph carefully and completely before administering a drug to a specific pa-
tient for the first time and review it any time a new drug is added to the patient’s drug
profile.

That’s it! A fast, complete, and accurate reference for anyone administering intravenous
medications. The spiral binding is specifically designed to lie flat, leaving your hands
free to secure needed supplies, prepare your medication, or even ventilate a patient while
you read the needed information.

Develop the “look it up” habit. Clear, concise language and simplicity of form con-
tribute to quick, easy use of this handbook. Before your first use, read the preface; it
contains lots of helpful information.

Check out the Intravenous Medications website for monographs no longer included in
this text and for other useful IV medication information:

http://evolve.elsevier.com/IVMeds
 Gahart’s 2021

INTRAVENOUS
MEDICATIONS
A Handbook for Nurses and Health Professionals

BETTY L. GAHART, RN
Nurse Consultant in Education
Napa, California
Former Director, Education and Training
Queen of the Valley Medical Center
Napa, California

ADRIENNE R. NAZARENO, PharmD

Clinical Manager, Department of Pharmacy
Queen of the Valley Medical Center
Napa, California

MEGHAN Q. ORTEGA, RN, BSN

Staff Nurse
Clovis Community Medical Center
Clovis, California

THIRTY-SEVENTH EDITION
 3251 Riverport Lane
St. Louis, Missouri 63043

GAHART’S 2021 INTRAVENOUS MEDICATIONS  ISBN: 978-0-323-75738-6

Copyright © 2021 by Elsevier Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage
and retrieval system, without permission in writing from the publisher. Details on how to
seek permission, further information about the Publisher’s permissions policies and our
arrangements with organizations such as the Copyright Clearance Center and the Copyright
Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by
the Publisher (other than as may be noted herein).

Notices
Practitioners and researchers must always rely on their own experience and knowledge
in evaluating and using any information, methods, compounds or experiments described
herein. Because of rapid advances in the medical sciences, in particular, independent
verification of diagnoses and drug dosages should be made. To the fullest extent of the
law, no responsibility is assumed by Elsevier, authors, editors or contributors for any
injury and/or damage to persons or property as a matter of products liability, negligence
or otherwise, or from any use or operation of any methods, products, instructions, or
ideas contained in the material herein.

Previous editions copyrighted 1973, 1977, 1981, 1984, 1988, 1989, 1990, 1991, 1993, 1994,
1995, 1996, 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004, 2005, 2006, 2007, 2008,
2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020

ISBN: 978-0-323-75738-6
ISSN: 1556-7443

Executive Content Strategist: Sonya Seigafuse

Senior Content Development Specialist: Danielle M. Frazier
Publishing Services Manager: Julie Eddy
Senior Project Manager: Jodi M. Willard
Design Direction: Margaret Reid

Printed in the United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 To my beloved husband,
Bill,
who passed away in September of 2019
and who always provided his patience, support,
and many hours of much-needed and appreciated assistance,
proofreading everything I wrote and checking all the page proofs
after I checked them to be extra sure I didn’t miss something;
and to our children,
Marty, Jeff, Debbie, Rick, and Teresa;
their spouses, Sally, Terri, Jim, and Mary;
and our grandchildren, Meghan, Laurie, Alex, Anne,
Kathryn, Lisa, Benjamin, Matthew, Claire, Neil, Scott, and Alan,
for their encouragement and understanding; and to our great-grandchildren,
Robyn, Daniel, and Layla, who have brought us much joy.

BLG

To my husband,
Greg,
for his loving support and encouragement,
and to my children,
Danielle, Bryan, Emily, and Mark, for allowing me the freedom
to pursue my professional practice.

ARN

To my husband,
Nate,
as well as my parents, Jim and Debbie,
for their unconditional love, support, and understanding.
To my grandparents Bill and Betty for their wisdom and guidance.
Lastly, to God, for His grace and for paving my path.

MQO
 NURSING AND PHARMACOLOGY CONSULTANTS
KIM HUBER, PharmD
Clinical Pharmacist
Memorial Medical Center
Modesto, California
GREGORY D. NAZARENO, PharmD
Staff Pharmacist
John Muir Medical Center
Concord, California
REVIEWERS
JAMES GRAVES, PharmD
Clinical Pharmacist
Inpatient Pharmacy
University of Missouri Health Care
Columbia, Missouri
BERNARD L. MARINI, PharmD, BCOP
Clinical Pharmacist Specialist—
Hematology
University of Michigan
Ann Arbor, Michigan
MERRILEE NEWTON, RN, MSN
Retired Administrative Director of Quality
and Infection Prevention
Alta Bates Summit Medical Center
Berkeley, California
RANDOLPH E. REGAL, BS, PharmD
Clinical Associate Professor
Adult Internal Medicine/Gastroenterology
University of Michigan College of
Pharmacy and Hospitals
Ann Arbor, Michigan
TRAVIS E. SONNETT, PharmD
Inpatient Pharmacy Supervisor
Mann-Grandstaff VA Medical Center;
Adjunct Clinical Faculty
Washington State University College of
Pharmacy
Pharmacotherapy
Spokane, Washington
ix
PREFACE

This Year 2021 edition marks the forty-eighth year of publication of Intravenous
­Medications. All previous editions are considered out-of-date.
In this thirty-seventh edition, a total of 24 new drugs approved by the FDA for intravenous
use have been incorporated. Sixteen of these new drugs are presented in individual mono-
graphs together in Appendix E. Five are new versions of previous drugs and incorporated
in that monograph (e.g., biosimilars). Three new drugs that were approved very close to
the last printing are now alphabetically included in the text.
The sixteen drugs in Appendix E include amisulpride (Barhemsys), a dopamine
antagonist for the treatment of postoperative nausea and vomiting; brexanolone
­
(­Zulresso), a receptor positive modulator for the treatment of postpartum depression
(PPD) in adults; cefiderocol (Fetroja), a cephalosporin antibacterial for the treatment of
complicated UTI and pyelonephritis; cetirizine hydrochloride (Quzyttir), a histamine
H1 antagonist for the treatment of acute urticaria in adults and pediatric patients
from 6 months of age; crizanlizumab-tmca injection (Adakveo), an anti-P-selectin mono-
clonal antibody to reduce the frequency of vaso-occlusive crises in sickle cell disease;
cysteine hydrochloride (Elcys), an amino acid to meet the nutritional needs of newborns
and in liver disease; cysteine hydrochloride (Nouress), indicated only for meeting the nu-
tritional needs of newborns; enfortumab-vedotin-ejfv (Padcev), an anti-nectin-4 antibody-
drug conjugate (ADC) antineoplastic for the treatment of metastatic urothelial cancer;
fam-­trastuzumab deruxtecan-nxki (Enhertu), a HER2-directed antibody and topoisomerase
inhibitor conjugate for the treatment of adults with unresectable or metastatic HER2-
positive breast cancer; golodirsen injection (Vyondys 53), an antisense oligonucleotide for
the treatment of Duchenne muscular dystrophy; imipenem, cilastin, and relebactam (Recar-
brio), an antibacterial (carbapenem, beta-lactamase inhibitor) for the treatment of cUTI
and cIAI in patients with no options; lefamulin (Xenleta), a pleuromutilin antibacterial for
the treatment of community-acquired pneumonia; meloxicam injection (Anjeso), a NSAID
for use in adults for the management of moderate to severe pain alone or in combination
with non-NSAID analgesics; onasemnogene abeparvovec-xioi (Zolgensma), an adeno-­
associated virus vector-based gene therapy for the treatment of spinal muscular dystro-
phy in pediatric patients; polatuzumab vedotin-piiq (Polivy), an anti-CD79b-directed anti-
neoplastic antibody-drug conjugate (ADC) for the treatment of diffuse large B-cell
lymphoma; and teprotumumab-trbw (Tepezza), an insulin-like growth factor-1 receptor
inhibitor for the treatment of thyroid eye disease.
The three drugs alphabetically included in the 2021 text include calaspargase
­pegol-mknl (Asparlas), an enzyme and antineoplastic agent for the treatment of ALL in
patients from 1 month to 21 years of age; ravulizumab-cwvz (Ultomiris), a monoclonal
antibody for the treatment of atypical hemolytic uremic syndrome; and tagraxofusp-erzs
(Elzonris), a CD123-directed cytotoxin antineoplastic for the treatment of blastic plasma-
cytoid dendritic cell neoplasm.
Azathioprine sodium has been transferred to the Evolve website. Methyldopate, ne-
siritide (Natrecor), torsemide (Demadex), and tromethamine (Tham-E) are no longer
available and have been deleted from the website or the text.
Four drugs are new biosimilars. They have been incorporated into the appropriate
drug monograph (bevacizumab, rituximab, and two trastuzumab products, respectively)
and include bevacizumab-bvzr (Zirabev), rituximab-pvvr (Ruxience), trastuzumab-anns
(Kanjinti), and trastuzumab-qyyp (Trazimera). Biosimilars are biological products that are
licensed (approved) by the FDA because they are highly similar to an already FDA-­
approved biological product (known as the reference product [e.g., trastuzumab (Her-
ceptin)]) but have allowable differences because they are made from living organisms.
Biosimilars also have no clinically meaningful differences in terms of safety, purity, and
potency from the reference product.
x
 PREFACE xi

Insulin in NS (Myxredlin), a premixed new formulation of insulin, has been incorpo-

rated in the insulin monograph.
Many new uses have been approved for established drugs, and numerous safety issues
have been identified by the FDA. All of these changes are incorporated so our readers
have the most current information available.
We continually strive to make information in this handbook informative and easier to
access. We continue to identify drugs with a Black Box Warning in the main heading of the
monograph. In addition, Black Box Warning statements are shaded in light gray and a
different typeface is used for instant identification wherever they appear in the text. Blue-
screened text emphasizes a special circumstance not covered by a Black Box Warning.
The FDA is now identifying Limitations of Use of drugs under Indications. Previously this
information has been placed in Precautions. Drugs granted accelerated approval are
­identified.
In the past, we have incorporated the Common Toxicity Criteria (CTC) provided by
the U.S. Department of Health and Human Services, the National Institutes of Health,
and the National Cancer Institute. This listing has been expanded and updated by these
organizations and is too expansive to be included in an appendix. Web access to this
material is available at www.cancer.gov. Search for CTCAE (Common Terminology
­Criteria for Adverse Events Version 4.0). Printed copies are available free of charge; call
1-800-4-CANCER (1-800-422-6237).
We are all aware that The Joint Commission and the Institute for Safe Medication Practices
(ISMP) have strongly emphasized various ways to reduce errors in drug ordering and ad-
ministration. One of their suggestions is to refer to a drug by both its generic and its trade
name. Intravenous Medications is the only reference that has consistently used both names
since its first publication. They also recommend that symbols (e.g., ,, ., #, $) be
spelled out. Although we have always spelled out most of them, they are now all spelled out.
The only exception is in charts when there isn’t room for the spelled-out version. The symbols
are included in the Key to Abbreviations (p. xx) if you need a refresher. Some of the other
ways in which we assist with safe administration are to spell out the word units, use Gm
instead of gm so it is not confused with mg, use mcg instead of mg, and drop all trailing
0s (as in 1.0) to prevent overdoses. The Joint Commission, the ISMP, the American Pharma-
ceutical Association, and several other organizations have identified “High-Alert Medications” (a
list of medications with the highest risk of injury when misused). The websites of these orga-
nizations contain considerable information and identify common risk factors and sug-
gested strategies. From the authors’ viewpoint, all drugs given by the IV route should be
considered high-alert medications. They have an immediate effect, are irretrievable, and
can cause life-threatening side effects with incorrect usage.
We join The Joint Commission in urging you to pay special attention to how tubes and
catheters are connected to patients. The Joint Commission challenges the manufacturers of
these devices to redesign them in ways that will make dangerous misconnection much
less possible. Look up The Joint Commission suggestions. A preventive measure not
mentioned by The Joint Commission is the simple practice of labeling every line at the point
of entry into the patient. This should be done whenever more than a single piece of tubing
(IV or other) is connected to a patient. Multiple-lumen catheters, 3-way stopcocks, chest
tubes, nasogastric tubes, and any other tubing entering the patient should be labeled with
its contents or use at the connection closest to the patient. In today’s health care settings,
patients frequently have multiple tubes inserted into their bodies. Correct labeling takes
only a few seconds at the time of insertion and saves many moments of precious time
every time the line needs to be accessed. Misconnection errors may be fatal; establish all
of these suggestions as a standard of practice, and misconnection errors will be avoided.
IV solutions prepared in flexible plastic containers have generated Safety Alerts by the FDA.
As a reminder: Do not hang IV infusions in flexible plastic containers in series connection,
do not pressurize IV infusions in flexible plastic containers to increase flow rates without
first fully evacuating residual air from the container, and do not use vented IV administration sets
with IV infusions in flexible plastic containers. All may result in air embolism.
xii PREFACE

Elsevier offers electronic versions of Intravenous Medications for handheld devices,

tablets, laptops, and desktop computers. These electronic versions are convenient and por-
table alternatives or supplements to the printed book. In addition, all drugs currently on
the Evolve IV Meds website (http://evolve.elsevier.com/IVMeds) for Intravenous Medica-
tions (because of space limitations for the print version) are now all incorporated in these
electronic versions in alphabetical order, so you have a complete package. Although the
electronic versions are accessible wherever you have an electronic device, keep in mind
that on some devices the entire monograph may not be visible at the same time. It is the
user’s responsibility to be familiar with the complete monograph and all aspects of each
drug before administration.
Health care today is an intense environment. The speed of change is overwhelming, but
the authors and publisher of Intravenous Medications have a commitment to provide all
health care professionals who have the responsibility to administer IV medications with an-
nual editions that incorporate complete, accurate, and current information in a clear, concise,
accessible, and reliable tool. FDA websites are monitored throughout the year and provide
many important updates, such as dose changes, new pediatric doses, additional disease-
specific doses, refinements in dosing applications, new indications, new drug interactions,
additional precautions, updates on post-marketing side effects, and new information on
­antidotes. Most drugs currently approved for intravenous use are included in the print ver-
sion or are on the Evolve website: http://evolve.elsevier.com/IVMeds/. (See pp. xiv and xv for a
listing.) Helpful charts for dilution and/or rate of administration are incorporated in selected
monographs. A General Dilution Chart to simplify calculations is found on the inside front
cover. Front matter material provides a Key to Abbreviations and Important IV Therapy
Facts.
Intravenous Medications is designed for use in critical care areas, at the nursing sta-
tion, in the office, in public health and home care settings, and by students and the armed
services. Pertinent information can be found in a few seconds. Take advantage of its
availability and quickly review every intravenous medication before administration.
The nurse is frequently placed in a variety of difficult situations. While the physician
verbally requests or writes an order, the nurse must evaluate it for appropriateness and
may need to prepare it, administer it, and observe the effects. Intravenous drugs are in-
stantly absorbed into the bloodstream, leading, it is hoped, to a prompt therapeutic ac-
tion, but the risk of an inappropriate reaction is a constant threat that can easily become
a frightening reality. It will be the nurse who must initiate emergency measures should
adverse effects occur. This is an awesome responsibility.
If, after reviewing the information in Intravenous Medications, you have any ques-
tions about any order you are given, clarify it with the physician, consult the pharmacist,
or consult your supervisor. The circumstances will determine whom you will approach
first. If the physician thinks it is imperative to carry out an order even though you have
unanswered questions, never hesitate to request that the physician administer the drug,
drug combination, or dose himself or herself. In this era of constant change, the physician
should be very willing to supply you, your supervisor, and/or the pharmacist with current
studies documenting the validity and appropriateness of orders.
All information presented in this handbook is pertinent only to the intravenous use of
the drug and not necessarily to intramuscular, subcutaneous, oral, or other means of
­administration.
Our sincere appreciation is extended to Gregory Nazareno, Kim Huber, and Merrilee
Newton for their ongoing participation in our efforts to bring you current, accurate, and
relevant information; and to Sonya Seigafuse, Danielle M. Frazier, Julie Eddy, Jodi M.
Willard, and Maggie Reid at Elsevier and Joe Rekart at Graphic World, who are the edi-
tors, production staff, and design staff that make the publishing of Intravenous Medica-
tions happen each year.
 PREFACE xiii

We also wish to thank you, the users of this reference. By seeking out this informa-
tion, you serve your patients’ needs and contribute to the safe administration of IV meds.
This is the final edition of Gahart’s Intravenous Medications. It’s been a great run
from 1973 to 2021. Thank you for your great support. Many sources, including the FDA,
now present information in a way that is relevant to its use, which was part of our origi-
nal goal so we have made our desired impact. Elsevier will continue to publish a similar
reference with a new team of authors. The future of health care is both complicated and
exciting.

    
 CONTENTS

Evolve website information, inside front cover

General Dilution Charts, i-ii

How to Use This Book, iii

Preface, x

Format and Content of Intravenous Medications, xvi

Key to Abbreviations, xx

Important IV Therapy Facts, xxii

Resources, xxiv

IV Drugs, 1

Appendix A
Recommendations for the Safe Use and Handling of Cytotoxic Drugs, 1368
Appendix B
FDA Pregnancy Categories, 1369
Appendix C
U.S. Department of Health and Human Services, National Institutes of Health, National
Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), 1369
Appendix D
Information for Patients Receiving Immunosuppressive Agents, 1370
Appendix E
Recently Approved Drugs, 1371
Index, 1417

Solution Compatibility Chart, last page and inside back cover

Selected Agents Not Included in the Book, Evolve website

Agalsidase Beta Antivenin Crotalidae Polyvalent Immune

Alfentanil Hydrochloride Fab (Ovine)
Alglucerase Arginine Hydrochloride
Alglucosidase Alfa—Lumizyme Ascorbic Acid
Alglucosidase Alfa—Myozyme Atracurium Besylate
Alpha1-Proteinase Inhibitor (Human) Axicabtagene Ciloleucel
Amifostine Azathioprine Sodium
Ammonium Chloride Benztropine Mesylate
Amobarbital Sodium Botulism Immune Globulin (Intravenous
Anthrax Immune Globulin Intravenous Human)
(Human) Caffeine and Sodium Benzoate
Antivenin (Latrodectus mactans) Capreomycin
Antivenin (Micrurus fulvius)

xiv
 CONTENTS xv

Centruroides (Scorpion) Immune F(ab')2 Orphenadrine Citrate

(Equine) Injection Oxacillin Sodium
Chloramphenicol Sodium Succinate Oxymorphone Hydrochloride
Chlorothiazide Sodium Pancuronium Bromide
Colistimethate Sodium Pentazocine (Lactate)
Conjugated Estrogens Pentetate Calcium Trisodium/Pentetate
Corticorelin Ovine Triflutate Zinc Trisodium
Crotalidae Immune F(ab9)2 (Equine) Phentolamine Mesylate
Dactinomycin Piperacillin Sodium
Deferoxamine Mesylate Plasma Protein Fraction
Defibrotide Pooled Plasma (Human)
Denileukin Diftitox Pralidoxime Chloride
Dextran 1 Protein (Amino Acid) Products
Diazoxide Protein C Concentrate (Human)
Dimenhydrinate Pyridostigmine Bromide
Diphtheria Antitoxin Pyridoxine (Vitamin B6)
Dolasetron Mesylate Quinidine Gluconate Injection
Doxapram Hydrochloride Raxibacumab
Edetate Calcium Disodium Regadenoson
Edetate Disodium Remifentanil Hydrochloride
Elosulfase Alfa Rocuronium Bromide
Ephedrine Sulfate Sebelipase Alfa
Ethacrynic Acid Secretin
Folic Acid Sermorelin Acetate
Fomepizole Injection Siltuximab
Fospropofol Disodium Sincalide
Gallium Nitrate Sodium Lactate
Galsulfase Sodium Nitrite and Sodium Thiosulfate
Hetastarch Sodium Phenylacetate and Sodium
6% Hydroxyethyl Starch 130/0.4 in NS Benzoate
Idursulfase Streptokinase
Imiglucerase/Velaglucerase Alfa Streptomycin Sulfate
Inamrinone Lactate Streptozocin
Interferon Alfa-2b, Recombinant Succinylcholine Chloride
Kanamycin Sulfate Taliglucerase Alfa
Laronidase Theophylline in D5W
Levocarnitine Ticarcillin Disodium and Clavulanate
Lincomycin Hydrochloride Potassium
Liothyronine Sodium Trabectedin
Mechlorethamine Hydrochloride Trace Metals
Meperidine Hydrochloride Treprostinil
Methocarbamol Vaccinia Immune Globulin Intravenous
Methoxy Polyethylene Glycol-Epoetin Beta (Human)
Methylene Blue Verteporfin
Minocycline Hydrochloride Vestronidase Alfa-vjbk Injection
Multivitamin Infusion Ziv-Aflibercept
Obiltoxaximab
 FORMAT AND CONTENT OF INTRAVENOUS MEDICATIONS

Designed to facilitate quick reference, each entry begins with the generic name of the drug
in boldface type. Drugs with a Black Box Warning are identified with a symbol in the main
heading. Phonetic pronunciations appear just below the generic name. Drug categories fol-
low. The primary category may be followed by additional ones representing the multiple
uses of a drug. Associated trade names are under the generic name. Boldface type and al-
phabetical order enable the reader to verify correct drug names easily. The use of a Cana-
dian maple leaf symbol ( ) after a trade name indicates availability in Canada only. The
pH is listed in the lower right-hand corner of the title section. While this information is not
consistently available, it is provided whenever possible. It represents the pH of the undi-
luted drug, the drug after reconstitution, or the drug after dilution for administration.
Headings within drug monographs are as follows:
USUAL DOSE: D  oses recommended are the usual range for adults unless specifically
stated otherwise. This information is presented first to enable the nurse to verify that the
physician order is within acceptable parameters while checking the order and before
preparation. If there are any questions, much time can be saved in clarifying them.
Pretreatment: A new subheading beginning with the 36th edition. It appears just under
the USUAL DOSE heading before the actual dose and alerts you to situations that must
or should be completed before administering the drug. Many of the newer drugs can
cause fetal harm, so you will find the statement “Verify pregnancy status” here. You
will also be alerted to baseline studies, pretesting, immunization, prehydration, and
other requirements indicated before treatment and will be referred to the place in the
monograph containing needed additional information.
Premedication: A subheading that notes premedication if required or suggested.
Dose: D
 rug name or a specific indication will be followed by the actual dose.
PEDIATRIC DOSE: Pediatric doses are specifically stated if they vary from mg/kg of body
weight or M2 dose recommended for adults. Not all drugs are recommended for use in
pediatric patients; see Maternal/Child for information on safety and effectiveness for use
in pediatric patients. To prevent unintentional overdose, a premixed solution such as
DUPLEX or Galaxy containers available in a specific dose (e.g., 1 Gm, 2 Gm) should be
used in pediatric patients only when the individual dose is the entire contents of the con-
tainer and not any fraction thereof.
INFANT AND/OR NEONATAL DOSE: Included if available and distinct from Pediatric Dose.
See Maternal/Child for information on safety and effectiveness for use in pediatric pa-
tients, including infants and neonates.
DOSE ADJUSTMENTS: Any situation that requires increasing or decreasing a dose is men-
tioned here. The range covers adjustments needed for elderly, debilitated, or hepatic or
renal impairment patients; adjustments required by race or gender; or adjustments re-
quired in the presence of other medications or as physical conditions are monitored.
DILUTION: Specific directions for dilution are given for all drugs if dilution is necessary
or permissible. Drugs, diluents, and solutions must be appropriate for IV use. Certain
medications may be available in more than one form (e.g., Advantage, Duplex); follow
manufacturer’s directions for reconstitution and stability. The manufacturing and ap-
proval of generics seems to be accelerating. They are usually similar to the trade version
but may differ slightly, so be sure to double-check the dose and dilution requirements.
Appropriate diluents are listed. The Solution Compatibility Chart on the inside back
cover has been expanded and updated. Diluents that are not identified in Dilution will be
listed in this chart. This is the only reference that provides calculation examples to sim-
plify dilution and accurate dose measurement. Charts are available in selected mono-
graphs. If recommendations for pediatric dilutions are available, they are listed. In some
situations mcg or mg/mL dilutions partially account for this variation. To prevent unin-
tentional overdose, a premixed solution such as DUPLEX or Galaxy containers available
xvi
 FORMAT AND CONTENT OF INTRAVENOUS MEDICATIONS xvii

in a specific dose (e.g., 1 Gm, 2 Gm) should be used in pediatric patients only when the
individual dose is the entire contents of the container and not any fraction thereof. If there
are any doubts, consult with the pharmacist and/or pediatric specialist. Generic dilution
charts for grams to milligrams and milligrams to micrograms are featured on the inside
front cover and facing page.
Filters: A
 subheading. Content here includes information included in prescribing in-
formation and information we have requested from manufacturers. Many drugs are
filtered during the manufacturing process. There are numerous variations in recom-
mendations for filtration after the manufacturing process. Filters are single-use one-
way streets and are most effective when used at the last stage of mixing, dilution, or
in-line as administered to the patient, or one or more of the above. Most manufactur-
ers expect that a drug distributed in an ampule will be filtered to eliminate the possi-
bility of glass being drawn into a syringe on withdrawal of the drug. This is always a
two-needle process. One process uses a standard needle to withdraw from the ampule;
that needle is then replaced with a needle filter to inject the drug into the diluent. If it
will not be added to a diluent, use the needle filter to withdraw from the ampule and
replace it with a new standard needle to administer. When questioned, many manu-
facturers suggest following a specific hospital’s standard, which may recommend that
a drug distributed as a powder be filtered either with a needle filter on withdrawal
from the vial, after reconstitution as added to the diluent, or with an in-line filter on
delivery to the patient. Some acknowledge that in selected situations (e.g., open heart
surgery) everything is filtered at some point before delivery to the patient. Although
these responses are helpful, none of them clarify specific information about a drug.
For questions, the manufacturer’s pharmacist is available.
Storage: A subheading. Content here includes such items as stability, refrigeration
versus room temperature, predilution versus postdilution. Newly approved generics
may have slight differences; check the manufacturer’s recommendations.
COMPATIBILITIES
The focus of this section is compatibility. Any drug not listed as compatible should be consid-
ered incompatible.
Beginning with this edition, only the manufacturer’s recommendations for compatibil-
ity or incompatibility are listed. No third-party compatibilities or incompatibilities are
listed. Manufacturer’s listing may include the manufacturer’s recommendation to admin-
ister separately from other drugs or the potential for reaction with some plastic infusion
bags or tubing. Other monographs include manufacturers’ statements regarding the po-
tential inactivation or inhibition of one drug on another. If the manufacturer provides no
information, that will be stated.
If there are other sources that list specific compatibilities dependent on concentration
or manufacturer, a statement to this follows so you know other compatibilities may exist.
Always consult a pharmacist.
Because compatibilities may be influenced by many factors (e.g., temperature, pH,
concentration, time together in solution, a specific order of mixing), it is imperative that
you verify compatibilities with your pharmacist. Knowledge is growing daily in this field, and
your pharmacist should have current information on the pharmacy computer or access to
extensive references. Many compatibility studies have been done by other parties for
both additive and Y-site compatibilities. Almost all are based on specific concentrations,
which may or may not relate to usual doses or recommended concentrations.
What steps should you consider before administering any drug?
• If the drug you wish to administer is not listed in the Compatibility section, consider it
to be incompatible. If administration is imperative and you have confirmed the physi-
cian’s order to administer, have consulted with your supervisor, and have consulted
with the pharmacy, you must turn off the infusing IV (at the stopcock or with a clamp
close to the Y-site), flush the line with a solution compatible to both drugs (and/or
solutions), administer the required drug, and flush the line again before turning the
previously infusing IV back on. Be sure to flush with enough solution before and after
xviii FORMAT AND CONTENT OF INTRAVENOUS MEDICATIONS

administration to completely clear the IV line, single lumen, or multilumen catheter.

If you are unable to discontinue the infusion IV, you must have another IV access
(e.g., a multilumen catheter, a second IV line, or a heparin lock). Some drugs actually
require separate tubing.
• If compatibilities are included in the package insert from the manufacturer, it will be
so stated. If the manufacturer lists drugs as compatible by additive or Y-site and
doesn’t list concentrations, this is a good assurance of compatibility. If concentrations
are listed, review the concentrations of both drugs to make sure they are within the
defined parameters.
• If the drug you wish to administer is listed in the Compatibility section of the access
you wish to use (e.g., additive or Y-site), you must consult with the pharmacist to confirm
any specific conditions that may apply. After your consultation, write the results of your
consultation regarding the specific directions for coadministering drugs on the pa-
tient’s medication record or nursing care plan so others will not need to retrace your
research steps when the medication is to be given again.
• When combining drugs in a solution (additives), always consider the required rate
adjustments of each drug. Can each drug produce the desired effect at the suggested
rate, or is continuous adjustment necessary for one drug, making the combination
impractical?
• Y-site means that the specific drug in a specific monograph is compatible at its Y-site
with an injection or an infusion containing one of the drugs listed under Y-site. The
reverse Y-site compatibility may not be true.
• Although some drugs may be listed as compatible at the Y-site, some drugs can be
administered at the Y-site only if they are further diluted in compatible solutions and
given as an infusion (e.g., potassium concentrates [e.g., acetates, chlorides, phos-
phates], saline solution in concentrations greater than 0.9% or NS, amino acids, and
dextrose solutions greater than 10% [unless in small amounts such as 50 mL dextrose
50% in insulin-induced hypoglycemia]).
• Because today’s hospital units are very specialized (e.g., cancer care, emergency
room, intensive coronary care, various intensive care units, transplant units, and or-
thopedic units to name just a few), nursing staff in each of these areas most likely
administer similar combinations of drugs to their patients. Take the initiative and re-
search the drug combinations that are most frequently used on your unit. Then consult with
the pharmacist and make your own compatibility chart for additives and Y-site (if applicable).
By creating a chart specific to your unit, you will limit the number of consults re-
quired with the pharmacist to combinations that fall outside the parameters you have
researched. This approach will save time for every nurse on your unit and will give
each of you the necessary compatibility information to administer the IV drug com-
binations specific to your unit.
• The Solution Compatibility Chart on the inside back cover has been expanded and
updated. Diluents that are not identified in Dilution will be listed in this chart.
RATE OF ADMINISTRATION: A  ccepted rates of administration are clearly stated. As a gen-
eral rule, a slow rate is preferred. 25-gauge needles aid in giving a small amount of
medication over time. Problems with rapid or slow injection rates are indicated here.
Adjusted rates for infants, children, or the elderly are listed when available. Charts are
available in selected monographs.
ACTIONS: C  lear, concise statements outline the origin of each drug, how it affects body
systems, its length of action, and methods of excretion. If a drug crosses the placental
barrier or is secreted in breast milk, it will be mentioned here if that information is
­available.
INDICATIONS AND USES: U  ses recommended by the manufacturer are listed. Limitations of
Use are now being identified by the manufacturer or FDA for some drugs. Unlabeled uses
are stated as such.
Limitation of Use: A subheading that identifies FDA statements of situations and/or
diagnoses limiting use.
 FORMAT AND CONTENT OF INTRAVENOUS MEDICATIONS xix

CONTRAINDICATIONS: C  ontraindications are those specifically listed by the manufacturer.

Consult with the physician if an ordered drug is contraindicated for the patient. The
physician may have additional historical information that alters the situation.
PRECAUTIONS: The section on precautions covers many areas of information needed be-
fore injecting any drug, including Black Box warnings from the prescribing information.
Most Black Box Warnings appear in this Precautions section; however, all actual Black
Box Warning statements are shaded in light gray and a different typeface is used for instant
identification wherever they appear in the text. The range of information in this category
covers all facets not covered under specific headings. Each listing is as important as the
next. To make it easier for spot checks (after reading the entire monograph), additional
subdivisions are included.
Monitor: A subheading that includes information such as required prerequisites for
drug administration, parameters for evaluation, and patient assessments.
Patient Education: A subheading that addresses only specific, important issues required
for short-term IV use. It is expected that the health professional will always review
the major points in the drug profile with any conscious patient, side effects to expect,
how to cope with them, when to report them, contraceptive requirements, special re-
quirements such as the intake of extra fluids, and an overall review of what the drug
does, why it is needed, and how long the patient can anticipate receiving it. Patient
Medication Guides approved by the FDA are available for most drugs, and it is recom-
mended that the patient review the Medication Guide whenever possible before begin-
ning treatment and repeat the review as indicated.
Maternal/Child: A
 subheading that addresses use in pregnancy, labor, and lactation;
safety for use in pediatric patients; and any special impact on infants and neonates.
Elderly: A subheading that is included whenever specific information impacting this
patient group is available. Always consider age-related organ impairment (e.g., car-
diac, hepatic, renal, insufficient bone marrow reserve), history of previous or con-
comitant disease or drug therapy, and route of excretion when determining dose and
evaluating side effects.
DRUG/LAB INTERACTIONS: Drug/drug or drug/lab interactions are listed here. To help
identify these interactions more easily, single drugs, drug categories when there are multiple
drugs, and specific tests are in boldface type. If a conflict with the patient’s drug profile is
noted, consult a pharmacist immediately. Increasing or decreasing the effectiveness of a
drug can be a potentially life-threatening situation. Check with the lab first on drug/lab
interactions; acceptable alternatives are usually available. After this consultation, notify
the physician if appropriate. To facilitate recognition, common trade names accompany
generic names or examples are presented for drug categories. No other reference consis-
tently provides this helpful information.
SIDE EFFECTS: I n some monographs, the most common side effects may be listed first,
followed by the most serious side effects. In all monographs, alphabetical order simpli-
fies confirmation that a patient’s symptom could be associated with specific drug use.
Specific symptoms of overdose are listed where available or distinct from usual doses.
Post-Marketing: A
 subheading that identifies post-marketing side effects reported that
have not been previously recorded in the prescribing information are listed.
ANTIDOTE: Specific antidotes are listed in this section if available. In addition, specific
nursing actions to reverse undesirable side effects are clearly stated—an instant refresher
course for critical situations.
Within a heading there may be references to other sections within an individual mono-
graph (e.g., see Precautions, see Monitor, see Dose Adjustments, see Maternal/Child).
These references indicate additional requirements and should be consulted before admin-
istering the drug.
 KEY TO ABBREVIATIONS

, less than CVA cerebrovascular accident

. more than CVP central venous pressure
1/4NS one-fourth normal saline (0.2%) D10NS 10% dextrose in normal saline
1/3NS one-third normal saline (0.33%) D10W 10% dextrose in water
1/2NS one-half normal saline (0.45%) D5/1/4NS 5% dextrose in one-quarter normal
ABGs arterial blood gases saline (0.2%)
ACE angiotensin converting enzyme D5/1/3NS 5% dextrose in one-third normal
ACT activated coagulation time saline (0.33%)
ACTH adrenocorticotropic hormone D5/1/2NS 5% dextrose in one-half normal saline
AF atrial fibrillation (0.45%)
A/G albumin-to-globulin ratio D5LR 5% dextrose in lactated Ringer’s
AIDS acquired immunodeficiency syndrome solution
ALT (SGPT) alanine aminotransferase D5NS 5% dextrose in normal saline
AMI acute myocardial infarction D5R 5% dextrose in Ringer’s solution
ANC absolute neutrophil count D5W 5% dextrose in water
aPTT activated partial thromboplastin time DC discontinued
ARDS adult respiratory distress syndrome/ DEHP diethylhexylphthalate
acute respiratory distress syndrome DIC disseminated intravascular
AST (SGOT) aspartate aminotransferase coagulation
AUC area under the curve dL deciliter(s) (100 mL)
AV atrioventricular dMMR deficient mismatch repair
BMD bone mass density DNA deoxyribonucleic acid
BP blood pressure ECG electrocardiogram
BSA body surface area EEG electroencephalogram
BUN blood urea nitrogen eGFR estimated glomerular filtration rate
BWFI bacteriostatic water for injection ESRD end-stage renal disease
C Celsius F Fahrenheit
Ca calcium FSH follicle-stimulating hormone
CABG coronary artery bypass graft GI gastrointestinal
CAD coronary artery disease GFR glomerular filtration rate
CAPD continuous ambulatory peritoneal GGT gamma-glutamyl transferase
dialysis Gm gram(s)
CBC complete blood cell count gr grain(s)
CDAD Clostridium difficile–associated gtt drop(s)
diarrhea GU genitourinary
CHF congestive heart failure Hb hemoglobin
Cl chloride Hct hematocrit
CMV cytomegalovirus HCV hepatitis C virus
CNS central nervous system Hg mercury
CO2 carbon dioxide HIV human immunodeficiency virus
COPD chronic obstructive pulmonary disease hr hour
CPK creatine-kinase HR heart rate
CrCl creatinine clearance HSCT hematopoietic stem cell transplant
CRF chronic renal failure IBW ideal body weight
CRT controlled room temperature (20° to ICU intensive care unit
25° C [68° to 77° F]) IgA immune globulin A
CSF cerebrospinal fluid IGIV immune globulin intravenous
C/S culture and sensitivity ÍL microliters, mL, mm3
CTCAE Common Terminology Criteria for IM intramuscular
Adverse Events INR International Normalized Ratio

xx
 KEY TO ABBREVIATIONS xxi

IP intrapleural PRCA pure red cell aplasia

IU international unit(s) PRES posterior reversible encephalopathy
IV intravenous syndrome
IVIG intravenous immune globulin PSVT paroxysmal supraventricular
K potassium tachycardia
KCl potassium chloride PT prothrombin time
kg kilogram(s) PTT partial thromboplastin time
L liter(s) PVC polyvinyl chloride; premature
lb pound(s) ventricular contraction
LDH lactic dehydrogenase R Ringer’s injection or solution
LFT liver function test RBC red blood cell
LH luteinizing hormone refrigerate temperature at 2° to 8° C (36° to
LR lactated Ringer’s injection or solution 46° F)
M molar RNA ribonucleic acid
M2 meter squared RPLS reversible posterior
MAO monoamine oxidase leukoencephalopathy syndrome
MAP mean arterial pressure RT room temperature
mcg microgram(s) RTS room-temperature stable
mCi millicurie(s) SA sinoatrial
mEq milliequivalent SC subcutaneous
Mg magnesium SIADH syndrome of inappropriate antidiuretic
mg milligram(s) hormone
MI myocardial infarction SOB shortness of breath
min minute SCr serum creatinine
mL milliliter S/S signs and symptoms
mmol millimole(s) SW or SWI sterile water for injection
mm3 cubic millimeters, mL, ÍL TEN toxic epidermal necrolysis
MDRSP multidrug-resistant Streptococcus TIA transient ischemic attacks
pneumoniae TLS tumor lysis syndrome
MRI magnetic resonance imaging TNA 3-in-1 combination of amino acids,
MSI-H microsatellite instability-high glucose, and fat emulsion
Na sodium TPN 2-in-1 combination of amino acids and
NaCl sodium chloride glucose; total parenteral nutrition
NCI National Cancer Institute; see CTCAE TRALI transfusion-related acute lung injury
ng nanogram (millimicrogram) TSH thyroid-stimulating hormone
NS normal saline (0.9%) TT thrombin time
NSAID nonsteroidal anti-inflammatory drug mL microliters, mm3, ÍL
NSCLC non–small-cell lung cancer ULN upper limits of normal
NSR normal sinus rhythm URI upper respiratory infection
N/V nausea and vomiting UTI urinary tract infection
OTC over-the-counter VEGF vascular endothelial growth factor
PAC premature atrial contraction VF ventricular fibrillation
Pao2 arterial oxygen pressure VS vital signs
PCA patient-controlled analgesia VT ventricular tachycardia
PCP Pneumocystis jiroveci pneumonia v/v volume-to-volume ratio
pg picogram WBC white blood cell
pH hydrogen ion concentration WBCT whole blood clotting time
PML progressive multifocal w/v weight-to-volume ratio
leukoencephalopathy w/w weight-to-weight ratio
PO by mouth/orally
 IMPORTANT IV THERAPY FACTS

• Read the Preface and Format and Contents sections at least once. They’ll answer many
of your questions and save time.
USUAL DOSE
• Doses calculated on body weight are usually based on pretreatment weight and not on
edematous weight.
• Normal renal or hepatic function is usually required for drugs metabolized by these
routes.
• Formula to calculate creatinine clearance (CrCl) from serum creatinine value (Cockcroft-
Gault equation):
Weight in kg  (140  Age in years)
Males:  CrCl
72  Serum creatinine (mg/dL)
Females: 0.85 3 Male CrCl value calculated from above formula.
Linear length or height (cm)
• Children: K 
SCr (mg/100 mL)
K for children .1 year of age 5 0.55
K for infants 5 0.45
• Lean Body Weight (LBW)
Males 5 50 kg 1 2.3 kg for each inch over 5 feet.
Females 5 45.5 kg 1 2.3 kg for each inch over 5 feet.
Children weighing 15 kg or less—Use actual body weight in kg.
• Formula to calculate body surface area (BSA):
Height (cm)  Weight (kg)
BSA (M2 ) 
3600
• To prevent unintentional overdose, a premixed solution such as DUPLEX or Galaxy
containers available in a specific dose (e.g., 1 Gm, 2 Gm) should be used in pediatric
patients only when the individual dose is the entire contents of the container and not any
fraction thereof.
DILUTION
• Check all labels (drugs, diluents, and solutions) to confirm appropriateness for IV use.
• Sterile technique is imperative in all phases of preparation.
• Use a filter needle when withdrawing IV meds from ampules to eliminate possible pieces
of glass.
• Pearls: 1 Gm in 1 Liter yields 1 mg/mL
1 mg in 1 Liter yields 1 mcg/mL
% of a solution equals the number of grams/100 mL
(5% 5 5 Gm/100 mL)
• Pediatric dilution: If you dilute 6.0 mg/kg in 100 mL, 1 mL/hr
equals 1.0 mcg/kg/min
If you dilute 0.6 mg/kg in 100 mL, 1 mL/hr
equals 0.1 mcg/kg/min
• To prevent unintentional overdose, a premixed solution such as DUPLEX or Galaxy
containers available in a specific dose (e.g., 1 Gm, 2 Gm) should be used in pediatric
patients only when the individual dose is the entire contents of the container and not any
fraction thereof.
• See charts on inside front cover.

xxii
 IMPORTANT IV THERAPY FACTS xxiii

• Do not use bacteriostatic diluents containing benzyl alcohol for neonates. May cause a
fatal toxic syndrome. S/S include CNS depression, hypotension, intracranial hemor-
rhage, metabolic acidosis, renal failure, respiratory problems, seizures.
• Ensure adequate mixing of all drugs added to a solution.
• When combining drugs in a solution (additives), always consider the required rate adjust-
ment of each drug.
• Examine solutions for clarity and any possible leakage.
• Frozen infusion solutions should be thawed at room temperature (25° C [77° F]) or under
refrigeration. Do not force by immersion in water baths or in the microwave. All ice
crystals must be melted before administration. Do not refreeze.
• Syringe prepackaging for use in specific pumps is now available for many drugs. Con-
centrations are often the strongest permissible, but length of delivery is accurate.
• Controlled room temperature (CRT) is considered to be 25° C (77° F). Most medications
tolerate variations in temperature from 15° to 30° C (59° to 86° F).
INCOMPATIBILITIES
• Some manufacturers routinely suggest discontinuing the primary IV for intermittent in-
fusion; usually done to avoid any possibility of incompatibility. Flushing the line before
and after administration may be indicated and/or appropriate for some drugs.
• The brand of intravenous fluids or additives, concentrations, containers, rate and order of
mixing, pH, and temperature all affect solubility and compatibility. Consult your phar-
macist with any question, and document appropriate instructions on care plan.
TECHNIQUES
• Do not hang IV infusions in flexible plastic containers in series connection, do not pressur-
ize IV infusions in flexible plastic containers to increase flow rates without first fully evacuat-
ing residual air from the container, and do not use vented IV administration sets with IV infu-
sions in flexible plastic containers. All may result in air embolism.
• Confirm patency of peripheral and/or central sites. Avoid extravasation.
• Avoid accidental arterial injection; can cause gangrene.
RATE OF ADMINISTRATION
• Life-threatening reactions (time-related overdose or allergy) are frequently precipitated
by a too-rapid rate of injection.
• If a common IV line is used to administer other drugs through the same IV line, flush the
IV line before and after each infusion with a compatible solution (e.g., NS, D5W). When
flushing before administration, be sure to flush with an amount adequate to clear the
previous drug (e.g., mL of drug or mL of lumen of catheter). When flushing after admin-
istration, be sure to flush with an amount at least equal to that of the drug administered
(e.g., mL of drug or mL of lumen of catheter).
PATIENT EDUCATION
• A well-informed patient is a great asset; review all appropriate drug information with
every conscious patient.
SIDE EFFECTS
• Reactions may be caused by a side effect of the drug itself, allergic response, overdose,
or the underlying disease process.
 RESOURCES

PUBLICATIONS
The following publications have been used as a resource to assemble the information
found in Intravenous Medications. Additional and more detailed information on drugs
may be found in these publications:
American Heart Association: Handbook of Emergency Cardiovascular Care for
Health Care Providers, 2015.
American Hospital Formulary Service Drug Information 2019, Bethesda, MD,
American Society of Health-System Pharmacists (updated via website).
ASHP Publications: Handbook on Injectable Drugs, ed 20, 2018, American Society
of Health-System Pharmacists, Inc.
Lexi-Comp’s Drug Information Handbook, ed 27, 2018-2019, Hudson, OH, American
Pharmacists Association.
Elsevier Guide to Oncology Drugs and Regimens, Huntington, NY, 2006, Elsevier.
The Johns Hopkins Hospital: The Harriet Lane Handbook, ed 20, St Louis, 2014,
Mosby.
Manufacturers’ literature.
WEBSITE RESOURCES
http://www.accessdata.fda.gov/scripts/cder/drugsatfda—Drug Approvals and Updates
http://www.fda.gov/safety/medwatch/default.htm—Safety Information
http://evolve.elsevier.com/IVMeds
http://www.cancer.gov—Common Terminology Criteria for Adverse Events ­(CTCAE)
http://www.blackboxrx.com—A listing of all drugs with a black box warning

xxiv
 e1

GENERIC DRUGS: A
ABATACEPT AMIODARONE HYDROCHLORIDE ANTITHROMBIN III (HUMAN)
ABCIXIMAB AMMONIUM CHLORIDE ANTITHROMBIN RECOMBINANT
ACETAMINOPHEN AMOBARBITAL SODIUM ANTI-THYMOCYTE GLOBULIN
ACETAZOLAMIDE SODIUM AMPHOTERICIN B ■ (RABBIT)
ACETYLCYSTEINE INJECTION AMPHOTERICIN B LIPID-BASED ANTIVENIN (LATRODECTUS
ACYCLOVIR PRODUCTS MACTANS)
ADENOSINE AMPICILLIN SODIUM ANTIVENIN (MICRURUS FULVIUS)
ADO-TRASTUZUMAB EMTANSINE AMPICILLIN SODIUM AND ANTIVENIN CROTALIDAE
AGALSIDASE BETA SULBACTAM SODIUM POLYVALENT IMMUNE FAB
ALBUMIN (HUMAN) ANGIOTENSIN II INJECTION (OVINE)
ALDESLEUKIN ANIDULAFUNGIN APREPITANT
ALEMTUZUMAB ANTHRAX IMMUNE GLOBULIN ARGATROBAN
ALFENTANIL HYDROCHLORIDE INTRAVENOUS (HUMAN) ARGININE HYDROCHLORIDE
AGLUCERASE ANTIHEMOPHILIC FACTOR ARSENIC TRIOXIDE
AGLUCOSIDASE ALFA (HUMAN ■ RECOMBINANT ■ ASCORBIC ACID
(LUMOSINE) RECOMBINANT [Fc FUSION ATEZOLIZUMAB
AGLUCOSIDASE ALFA (MYOSINE) PROTEIN] ■ RECOMBINANT ATRACURIUM BESYLATE
ALLOPURINOL SODIUM [PEGYLATED] ■ ATROPINE SULFATE
ALPHA1-PROTEINASE INHIBITOR RECOMBINANT [SINGLE AVELUMAB
(HUMAN) CHAIN] ■ RECOMBINANT AXICABTAGENE CILOLEUCEL
ALPROSTADIL [PORCINE SEQUENCE]) SUSPENSION
ALTEPLASE ANTIHEMOPHILIC FACTOR ■ AZACITIDINE
AMIFOSTINE VON WILLEBRAND FACTOR AZATHIOPRINE SODIUM
AMIKACIN SULFATE COMPLEX (HUMAN) AZITHROMYCIN
AMINOCAPROIC ACID ANTI-INHIBITOR COAGULANT AZTREONAM
AMINOPHYLLINE COMPLEX
 1

ABATACEPT Antirheumatic
(a-BAY-ta-sept) Disease-modifying agent
Selective T-cell
costimulation blocker

Orencia pH 7.2 to 7.8

USUAL DOSE
Pretreatment: Pretesting required; see Monitor. See Maternal/Child.
Dose is based on body weight in kilograms as shown in the following chart. After
the ­initial dose, repeat administration at 2 and 4 weeks. Administer every 4 weeks there-
after. May be used as monotherapy or concomitantly with disease-modifying anti-­
rheumatic drugs (DMARDs) other than TNF antagonists; see Contraindications and
Drug Interactions. May be given by SC injection or as an IV infusion; formulation and
dose are different; see Indications and prescribing information.

Abatacept Adult Dosing Guidelines

Body Weight (kg) Dose (mg) Number of Vials
,60 kg 500 mg 2 vials
60 to 100 kg 750 mg 3 vials
.100 kg 1,000 mg 4 vials

Patients transitioning from IV therapy to subcutaneous administration should administer

the first subcutaneous dose instead of the next scheduled IV dose. Abatacept is dosed
weekly in the subcutaneous regimen. When administered for treatment of rheumatoid
arthritis, it may be initiated with or without an IV loading dose. If the subcutaneous
regimen is initiated with an IV loading dose, determine loading dose as outlined in the
previous chart. The first subcutaneous injection should be administered within a day of
the IV loading dose. A loading dose is not used when administered for treatment of pso-
riatic arthritis.
PEDIATRIC DOSE
May be given by SC injection (2 years of age and older) or as an IV infusion (6 years of
age and older) in pediatric patients. Formulation and dose are different; see Indications
and prescribing information. When administered subcutaneously, do not administer an IV
loading dose. May be used as monotherapy or concomitantly with methotrexate.
Pediatric patients 6 to 17 years of age who weigh less than 75 kg: 1
 0 mg/kg/dose based on
patient’s body weight at each administration. After the initial dose, repeat administration
at 2 and 4 weeks. Administer every 4 weeks thereafter.
Pediatric patients 6 to 17 years of age who weigh more than 75 kg: S ee Usual Dose and the
Abatacept Adult Dosing Guidelines chart. Do not exceed a maximum dose of 1,000 mg.
DOSE ADJUSTMENTS
There is a trend toward a higher clearance with increasing body weight; see Usual Dose.
No specific dose adjustments are required based on age or gender when corrected for
body weight. n The effects of renal or hepatic impairment have not been studied.
DILUTION
Using ONLY the silicone-free disposable syringe provided with each vial and an 18- to
21-gauge needle, reconstitute each 250-mg vial with 10 mL SWFI; final concentration is
25 mg/mL. (If reconstituted with a siliconized syringe, the solution must be discarded.)
Direct stream of SWFI toward side of vial. Do not use vial if vacuum is not present.
Rotate or swirl vial gently until contents have dissolved. Do not shake. After dissolution,
vent vial with a needle to dissipate any foam that may be present. Solution should
2 ABATACEPT

be clear and colorless to pale yellow. Reconstituted solution must be further diluted to
100 mL as follows: From a 100-mL infusion bag or bottle, withdraw a volume of NS
equal to the volume of reconstituted abatacept solution required for the patient’s dose (for
2 vials, remove 20 mL; for 3 vials, remove 30 mL; for 4 vials, remove 40 mL). Using the
same silicone-free disposable syringe provided, slowly add the reconstituted abatacept into
the infusion bag or bottle. Mix gently.
Orencia prefilled syringes and Orencia ClickJet autoinjectors are intended for subcu-
taneous use only and are not intended for IV ­infusion.
Filter: A
 dministration through a 0.2- to 1.2-micron, nonpyrogenic, low–protein binding
filter is required.
Storage: R  efrigerate unopened vials at 2° to 8° C (36° to 46° F). Do not use beyond ex-
piration date. Protect from light by storing in original packaging. Before administration,
the diluted solution may be stored at RT or refrigerated; however, infusion of the diluted
solution should be completed within 24 hours of reconstitution. Discard diluted solution
if not administered within 24 hours. Any unused portion in a vial must be discarded.
COMPATIBILITY
Manufacturer states, “Should not be infused concomitantly in the same intravenous line
with other agents.” Compatibility studies have not been performed.
RATE OF ADMINISTRATION
Administration through a 0.2- to 1.2-micron, nonpyrogenic, low–protein binding filter is
required.
A single dose equally distributed over 30 minutes.
ACTIONS
A selective T-cell costimulation modulator. A soluble fusion protein that consists of
the extracellular domain of human cytotoxic, T-lymphocyte–associated antigen 4 linked
to the modified Fc portion of human immunoglobulin G1 (IgG1). Produced by recom­
binant DNA technology. Acts as a selective biologic response modulator by inhibiting
T-lymphocyte activation. Activated T-lymphocytes are implicated in the pathogenesis of
rheumatoid arthritis and psoriatic arthritis. Abatacept reduces pain and joint inflamma-
tion and slows the progression of structural damage to bone and cartilage. Mean half-life
is 13.1 days (range 8 to 25 days).
INDICATIONS AND USES
Reduce the S/S, induce a major clinical response, inhibit the progression of structural
damage, and improve the physical function in adult patients with moderately to severely
active rheumatoid arthritis. May be used as monotherapy or concomitantly with
DMARDs other than TNF antagonists. May be given IV or SC. Adult infusion patients
may transition to SC injection; see prescribing information. n Reduce the S/S in pediat-
ric patients 2 years of age and older with moderately to severely active polyarticular ju-
venile idiopathic arthritis. May be used as monotherapy or concomitantly with metho-
trexate. SC injection may be used in pediatric patients 2 years of age and older. IV dosing
has not been studied in patients younger than 6 years of age; see prescribing informa-
tion. n Treatment of adult patients with active psoriatic arthritis. May be used with or
without nonbiologic DMARDs.
Limitation of use: Should not be administered concomitantly with TNF antagonists (e.g.,
adalimumab [Humira], etanercept [Enbrel]) or other biologic rheumatoid arthritis ther-
apy, such as anakinra (Kineret).
CONTRAINDICATIONS
Manufacturer states, “None.” Consider known hypersensitivity to abatacept or any of its
components (maltose, monobasic sodium phosphate). See Limitation of Use and Drug/
Lab Interactions.
PRECAUTIONS
Concurrent use with a TNF antagonist (e.g., adalimumab [Humira], etanercept [Enbrel])
is associated with an increased risk of infections with no associated increased efficacy
when compared with use of the TNF antagonist alone. Concurrent use is not recom-
mended; see Limitation of Use, Contraindications, and Drug/Lab Interactions. n Hyper-
 ABATACEPT 3

sensitivity reactions, including anaphylaxis, have been reported and can occur after the
first infusion. Emergency medical equipment and medications for treating these reactions
must be readily available. n Serious infections, including sepsis and pneumonia, have
been reported; some have been fatal. Patients receiving concomitant immunosuppressive
therapy may be at increased risk. n Use caution in patients with a history of recurrent
infections, underlying conditions that may predispose them to infections, or chronic, la-
tent, or localized infections; see Monitor. n Anti­rheumatic therapies have been associ-
ated with hepatitis B reactivation. Screening for viral hepatitis should be done before
starting therapy with abatacept. Patients who screened positive for hepatitis were ex-
cluded from clinical studies. n Use with caution in patients with COPD. May be at in-
creased risk for developing respiratory adverse events (e.g., COPD exacerbation, cough,
dyspnea, rhonchi). n As with all therapeutic proteins, there is a potential for immuno­
genicity. A small number of patients have developed binding antibodies to abatacept. No
correlation of antibody development to clinical response or adverse events has been ob-
served. n T-cells mediate cellular immune responses. Drugs that inhibit T-cell activa-
tion, including abatacept, may affect patient defenses against infection and malignancies.
The impact of abatacept on the development and course of malignancies is not fully
understood. n See Maternal/Child.
Monitor: E  valuate patients for latent tuberculosis (TB) with a TB skin test. Patients testing
positive in TB screening should be treated with a standard TB regimen before initiating
therapy with abatacept. n Screening for viral hepatitis should be performed before initi-
ating therapy with abatacept. n Monitor for S/S of infection, especially if transitioning
patient from TNF antagonist therapy to therapy with abatacept. Discontinue therapy if a
serious infection develops. n Monitor COPD patients for worsening of respiratory
­status. n Monitor for S/S of hypersensitivity or infusion-related reactions; see Side
­Effects. n See Precautions and Drug/Lab Interactions.
Patient Education: R  ead manufacturer’s patient information sheet before each infusion.
n Review disease states, medication list, and vaccination status with physician; see Pre-

cautions. n Report S/S of allergic reaction (e.g., rash, itching, wheezing), infusion reac-
tion (e.g., dizziness, headache), or infection promptly. Discuss previous infections, cur-
rent infections, or exposure to TB.
Maternal/Child: Safety for use in pregnancy has not been established. Use caution. n There
is no information regarding the presence of abatacept in human milk, the effects on the
breast-fed infant, or the ­effects on milk production. n A pregnancy registry has been es-
tablished; contact manufacturer. n Safety and effectiveness for use in pediatric patients
under 2 years of age not established. IV dosing has not been studied in patients younger
than 6 years of age. n Safety and effectiveness for uses other than juvenile idiopathic ar-
thritis in pediatric patients have not been established. n Patients with juvenile idiopathic
arthritis should be brought up-to-date with all immunizations before initiating therapy
with ­abatacept. n ­Because it is unknown whether abatacept can cross the p­ lacenta and
because it is an immunomodulatory agent, the safety of administering live vaccines to
infants exposed to abatacept in utero is unknown. Consider risk versus ­benefit.
Elderly: S pecific differences in safety and efficacy not noted. The frequency of serious
infection and malignancy in patients over 65 years of age was greater than for those
under age 65. However, there is a higher incidence of infection and malignancy in the
elderly population in general. Use caution; see Precautions.
DRUG/LAB INTERACTIONS
Formal drug interaction studies have not been conducted. n Has been used with metho-
trexate, NSAIDs (e.g., naproxen [Naprosyn, Aleve], ibuprofen [Motrin, Advil]), and
corticosteroids (e.g., prednisone). n Methotrexate, NSAIDs, corticosteroids, and TNF
antagonists do not appear to influence abatacept clearance. n Concurrent use with a TNF
antagonist (e.g., adalimumab [Humira], etanercept [Enbrel], infliximab [Remicade]) is
associated with an increased risk of serious infections and no significant additional effi-
cacy over use of the TNF antagonist alone. Concurrent use is not recommended. n With
the IV formulation, falsely elevated blood glucose readings may occur on the day of the
4 ABATACEPT

infusion with specific blood glucose monitoring systems that react to drug products contain-
ing maltose. IV formulation contains maltose; SC formulation does not contain maltose;
see prescribing information. n Safety and efficacy of concurrent use with anakinra (Ki-
neret) has not been established. Concurrent use is not recommended. n Live virus vac-
cines should not be given concurrently with or within 3 months of abatacept. n May
blunt the effectiveness of some vaccinations.
SIDE EFFECTS
In adult and pediatric patients, side effects are similar in type and frequency. The most
commonly reported side effects are headache, nasopharyngitis, nausea, and upper respi-
ratory tract infections. The most serious adverse effects are infections and malignancies.
Infections are the most likely adverse event to cause interruption or discontinuation of
therapy. Acute infusion-related reactions (cough, dizziness, dyspnea, flushing, headache,
hypertension, hypotension, nausea, pruritus, rash, urticaria, wheezing) have been re-
ported and usually occur within 1 hour of the infusion. Hypersensitivity reactions
(­anaphylaxis [rare], dyspnea, hypotension, urticaria) have been reported, usually within
24 hours of infusion. Other reactions include back or extremity pain, COPD exacerba-
tion, dyspepsia, immunogenicity (antibody formation), and rhonchi.
Post-Marketing: N
 ew or worsening psoriasis and vasculitis (including cutaneous vasculitis
and leukocytoclastic vasculitis).
ANTIDOTE
Notify physician of any side effects; most will be treated symptomatically. During clini-
cal studies, most infusion-related reactions were mild to moderate, and therapy was
discontinued in very few patients. Discontinue abatacept for any serious reaction or in-
fection. Therapy may need to be interrupted in patients who develop infections. Treat
infusion and hypersensitivity reactions as indicated (e.g., oxygen, diphenhydramine,
epinephrine, corticosteroids, vasopressors, and/or fluids). Resuscitate as necessary.

ABCIXIMAB Antiplatelet agent

(ab-SIX-ih-mab) Antithrombotic
Monoclonal antibody

ReoPro pH 7.2

USUAL DOSE
Pretreatment: Baseline studies required; see Monitor.
Administered concomitantly with heparin and aspirin as described in Clinical Studies;
see prescribing information.
Percutaneous coronary intervention: 0.25 mg/kg as an IV bolus administered 10 to 60 min-
utes before percutaneous coronary intervention (PCI). Follow with a continuous infusion
of 0.125 mcg/kg/min (weight adjusted) to a maximum of 10 mcg/min (non–weight ad-
justed) for 12 hours.
Unstable angina not responding to conventional medical therapy with planned PCI within
24 hours: 0.25 mg/kg as an IV bolus followed by an 18- to 24-hour continuous infusion
of 10 mcg/min. Discontinue abciximab 1 hour after the PCI.
Based on an integrated analysis of data from all studies, the following guidelines may
be used to minimize the risk for bleeding:
• When abciximab is initiated 18 to 24 hours before PCI, the aPPT should be main-
tained between 60 and 85 seconds during the abciximab and heparin infusion period.
• During PCI, the ACT should be maintained between 200 and 300 seconds.
• If anticoagulation is continued in these patients following PCI, the aPTT should be
maintained between 55 and 75 seconds.
 ABCIXIMAB 5

DILUTION
Available in 5-mL vials (2 mg/mL). Solution must be clear. Must be filtered with a non-
pyrogenic, low–protein binding, 0.2- or 5-micron filter before administering the bolus
and a 0.2- or 0.22-micron filter before administering the infusion; see Filters. Filtering of
the infusion may be done during preparation or at administration, using the appropriate
in-line filter. Do not shake.
IV injection: B
 olus injection may be given undiluted.
Infusion: W ithdraw desired dose and further dilute with NS or D5W (5 mL [10 mg] di-
luted with 250 mL NS or D5W equals 40 mcg/mL).
Filters: M
 ust be filtered before administering the bolus and the infusion. Bolus may be
given using a sterile, nonpyrogenic, low–protein binding, 0.2- or 5-micron syringe
filter. Filtering of the infusion may be done during preparation using a sterile, nonpy-
rogenic, low–protein binding, 0.2- or 5-micron syringe filter or at administration using
an in-line, sterile, nonpyrogenic, low–protein binding, 0.2- or 0.22-micron filter; see
­Dilution.
Storage: Refrigerate before use. Do not freeze. Check expiration date on vial. Contains
no preservative; discard any unused portion.
COMPATIBILITY
According to the manufacturer, no incompatibilities have been shown with IV fluids or
commonly used cardiovascular drugs; however, administration through a separate IV line
and not mixing with other medications is recommended. No incompatibilities observed
with glass bottles or polyvinyl chloride bags and administration sets.
Other sources suggest a few specific compatibilities dependent on concentration and
manufacturer; consult a pharmacist.
RATE OF ADMINISTRATION
IV injection: A
 n initial dose as a bolus injection; filtration required.
Infusion: S ee Usual Dose. Must be administered through an in-line, nonpyrogenic, low–
protein binding filter (0.2 or 0.22 microns), if not done during preparation, and controlled
by a continuous infusion pump. A 40-mcg/mL solution (10 mg in 250 mL) at a rate of
10.5 mL/hr will deliver 7 mcg/min, and 15 mL/hr will deliver 10 mcg/min. Discard un-
used portion at the end of the infusion.
ACTIONS
The fab fragment of the chimeric human-murine monoclonal antibody, abciximab binds
to the glycoprotein GPIIb/IIIa receptor of human platelets and produces rapid dose-
dependent inhibition of platelet function. It inhibits platelet aggregation by preventing
the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/
IIIa receptor sites on activated platelets. Also binds to the vitronectin receptor found on
platelets and on the endothelial and smooth muscle cells of the vessel wall. The vitronec-
tin receptor mediates the procoagulant properties of platelets and the proliferative proper-
ties of vascular endothelial and smooth muscle cells. Onset of action is rapid, reducing
platelet aggregation to less than 20% of baseline within 10 minutes. Inhibition of platelet
function is temporary f­ollowing a bolus dose, but can be sustained at greater than 80%
by continuous IV infusion. Has prevented acute thrombosis and resulted in lower rates of
thrombosis as compared to aspirin and/or heparin. Initial half-life is 10 minutes. Second
phase half-life is 30 minutes. After the infusion is ended, platelet function generally
­recovers gradually over 48 hours. In most patients, bleeding time returns to less than
12 minutes within 12 to 24 hours. Some abciximab remains in the circulation for 15 days
or more.
INDICATIONS AND USES
An adjunct to PCI for the prevention of cardiac ischemic complications in patients un-
dergoing PCI and in patients with unstable angina not responding to conventional medi-
cal therapy when PCI is planned within 24 hours. Safety and effectiveness of abciximab
use in patients not undergoing PCI have not been established. Used concurrently with
aspirin and heparin.
6 ABCIXIMAB

CONTRAINDICATIONS
Active internal bleeding, administration of oral anticoagulants (e.g., warfarin [Couma-
din]) within 7 days unless PT is at or less than 1.2 times control, aneurysm, arteriovenous
malformation, bleeding diathesis, clinically significant GI or GU bleeding within
6 weeks, history of CVA within 2 years, history of CVA with significant residual neuro-
logic deficit, history of vasculitis (presumed or documented), hypertension (severe and
uncontrolled), intracranial neoplasm, known hypersensitivity to any component of
­abciximab or to murine proteins, major surgery or trauma within 6 weeks, thrombocyto-
penia (less than 100,000/mm3), or the use of IV dextran before PCI or intent to use it
during PCI.
PRECAUTIONS
Administered only in the hospital under the direction of a physician knowledgeable in its
use and with appropriate diagnostic, laboratory, and surgical facilities available. n May
cause major bleeding complications (e.g., retroperitoneal bleeding, spontaneous GI and
GU bleeding, bleeding at the arterial access site). Fatalities have occurred. n Risk of
bleeding may be minimized by using weight-adjusted dosing of abciximab and low-dose
weight-adjusted doses of heparin, with adherence to stricter anticoagulation guidelines,
careful vascular access site management, discontinuation of heparin after the procedure,
and early sheath removal. n Incidence of major bleeding is increased in patients receiv-
ing heparin, other anticoagulants, or thrombolytics (e.g., alteplase [tPA], reteplase [r-PA],
streptokinase). Consider if benefits will outweigh risks, and proceed with extreme cau-
tion if use is considered necessary. n Incidence of major bleeding is also increased if
PCI occurs within 12 hours of the onset of symptoms of an acute MI, if the PCI proce-
dure is prolonged (lasting more than 70 minutes), or if PCI procedure fails. n Extreme
care must be taken in accessing the femoral artery for femoral sheath placement. Only
the anterior wall of the femoral artery should be punctured (avoid a Seldinger [through
and through technique] for obtaining sheath access). n Avoid femoral vein sheath place-
ment if possible. n Hypersensitivity reactions, including anaphylaxis, can occur at any
time (a protein solution). Emergency drugs and equipment must always be available.
n Thrombocytopenia, including severe thrombocytopenia, has been reported. Usually

seen within the first 24 hours of abciximab administration, but some cases have been
reported up to 2 weeks after administration. n Administration may result in the forma-
tion of human antichimeric antibody (HACA). Can cause hypersensitivity reactions in-
cluding anaphylaxis, thrombocytopenia, or diminished benefit if abciximab is readmin-
istered at another time or other monoclonal antibodies are administered. Incidence and
severity of thrombocytopenia may be increased with readministration. n See Drug/Lab
Interactions.
Monitor: B
 efore initiating, obtain results of baseline CBC, platelet count, PT, ACT, and
aPTT. Type and cross-match would also be appropriate. n Monitor heparin anticoagula-
tion (ACT or aPTT) and PT closely. n While a femoral sheath is in place, the patient
must be on strict bed rest, head of the bed should be less than 30 degrees, and the ap-
propriate limb(s) restrained in a straight position. Monitor sheath insertion site(s) and
distal pulses of affected leg(s) frequently while sheath is in place and for 6 hours after
removal. Measure any hematoma and monitor for enlargement. n Monitor platelet count
2 to 4 hours following the bolus dose and at 24 hours or before discharge, whichever is
first. More frequent monitoring may be indicated. n Monitor patient carefully and fre-
quently for signs of bleeding; take vital signs (avoiding automatic BP cuffs); observe any
invaded sites at least every 15 minutes (e.g., sheaths, IV sites, cutdowns, punctures, Fo-
leys, NGs); watch for hematuria, hematemesis, hemoptysis, bloody stool, petechiae, he-
matoma, flank pain, muscle weakness; and do neuro checks every hour. Continue until
clotting functions move toward normal. n Use care in handling patient; avoid arterial
puncture, venipuncture, and IM injection. Use extreme precautionary methods and only
compressible sites if these procedures are absolutely necessary. Apply pressure for 30
minutes to any invaded site and then apply pressure dressings. Saline or heparin locks are
suggested to facilitate blood draws. n Minimize use of urinary catheters, nasotracheal
 ABCIXIMAB 7

intubation, nasogastric tubes, and automatic blood pressure cuffs. Discontinue heparin
after PCI and remove sheath no sooner than 2 hours and no later than 6 hours after
heparin is discontinued (aPTT must be at or less than 50 seconds or ACT at or less than
175 seconds). After removal, apply pressure to the femoral artery for at least 30 minutes.
When hemostasis is confirmed, apply a pressure dressing. Maintain strict bed rest for at
least 6 to 8 hours after sheath removal and/or abciximab is discontinued or 4 hours after
heparin is discontinued, whichever is later. n Throughout process medicate as needed
for back or groin pain and nausea or vomiting. n Remove pressure dressing before am-
bulation. n In the event of serious, uncontrolled bleeding or the need for emergency
surgery, discontinue abciximab. Platelet function may be partly restored with platelet
transfusions. n See Precautions, Drug/Lab Interactions, and Antidote.
Patient Education: Compliance with all measures to minimize bleeding (e.g., strict bed
rest, positioning) is imperative. n Avoid use of razors, toothbrushes, and other sharp
items. n Use caution while moving to avoid excessive bumping. n Report all episodes
of bleeding and apply local pressure if indicated. n Expect oozing from IV sites.
Maternal/Child: U
 se during pregnancy only if clearly needed. n Safety for use during
breast-feeding not established. Not known if it is secreted in breast milk; use caution. n
Safety and effectiveness for use in pediatric patients not established.
Elderly: No overall difference in safety or efficacy observed in patients between 65 and
75 years of age as compared with younger patients. Insufficient data to determine
whether patients age 75 or older respond differently. n Increased risk of major ­bleeding
complications if weight less than 75 kg; see Precautions. n Consider age-­related organ
impairment, concomitant disease, or drug therapy; may also increase risk of bleeding.
DRUG/LAB INTERACTIONS
Formal drug interaction studies have not been conducted. n Use with extreme caution
with other drugs that affect hemostasis (e.g., thrombolytics [e.g., alteplase (tPA), strepto-
kinase], anticoagulants [e.g., heparin, warfarin (Coumadin)], NSAIDs [e.g., ibuprofen
(Advil, Motrin), naproxen (Aleve, Naprosyn)], platelet aggregation inhibitors [e.g., clopi-
dogrel (Plavix), dipyridamole (Persantine), ticlopidine (Ticlid)] and other glycoprotein
GPIIb/IIIa receptor antagonists [e.g., eptifibatide (Integrilin), tirofiban (Aggrastat)], and se-
lected antibiotics [e.g., cefotetan]). n Dextran solutions increased the risk of major bleed-
ing events when used concurrently with abciximab; see Contraindications. n HACA titer
may precipitate an acute hypersensitivity reaction with other diagnostic or therapeutic
monoclonal antibodies (e.g., muromonab-CD3). n Has been administered to patients with
ischemic heart disease treated concomitantly with heparin, warfarin, beta-adrenergic re-
ceptor blockers (e.g., metoprolol [Lopressor]), calcium channel antagonists (e.g., diltia-
zem [Cardizem]), angiotensin-converting enzyme inhibitors (e.g., enalapril [Vasotec]),
nitrates, ticlopidine (Ticlid), and aspirin.
SIDE EFFECTS
May cause major bleeding incidents (e.g., femoral artery or other access site, intracranial
hemorrhage, spontaneous gross hematuria and other GU bleeds, spontaneous hemateme-
sis and other GI bleeds, pulmonary alveolar hemorrhage, retroperitoneal bleeding). De-
creases in hemoglobin greater than 5 Gm/dL or intracranial hemorrhage were defined as
major during trials. Thrombocytopenia is common and may require platelet transfusion.
Abdominal pain, back pain, bradycardia, chest pain, headache, hypotension, nausea,
peripheral edema, positive HACA response, hypersensitivity reactions (including ana-
phylaxis), puncture site pain, and vomiting may occur. Other side effects that may occur
are anemia, arrhythmias (e.g., atrial fibrillation/flutter, bradycardia, complete AV block,
supraventricular tachycardia, ventricular PVCs, tachycardia, or fibrillation), confusion,
hyperesthesia, intermittent claudication, leukocytosis, limb embolism, pericardial effu-
sion, pleural effusion or pleurisy, pneumonia, pulmonary edema, pulmonary embolism,
and visual disturbances.
8 ABCIXIMAB

ANTIDOTE
Stop the infusions of abciximab and heparin if any serious bleeding not controllable with
pressure occurs. Stop infusion in patients with failed PCI. Stop infusion if a hypersensi-
tivity reaction occurs. Treat hypersensitivity reactions as indicated; may require epineph-
rine, airway management, oxygen, IV fluids, antihistamines (e.g., diphenhydramine
[Benadryl]), corticosteroids (e.g., hydrocortisone sodium succinate [Solu-Cortef]), and
pressor amines (e.g., dopamine). Keep physician informed. If an acute platelet decrease
occurs (less than 100,000/mm3 or a decrease of at least 25% from pretreatment value),
obtain additional platelet counts in separate tubes containing ethylenediaminetetraacetic
acid (EDTA), citrate, and heparin. This is to exclude pseudothrombocytopenia due to
anticoagulant interaction. If true thrombocytopenia is verified, discontinue abciximab
immediately. Platelet transfusions may be required. Heparin and aspirin should also be
avoided if the platelet count drops below 60,000/mm3.

ACETAMINOPHEN Antipyretic
(ah-SEAT-ah-MIN-oh-fen) Analgesic

Ofirmev pH 5.5

USUAL DOSE
Pretreatment: Baseline studies may be indicated; see Monitor.
May be given as a single or repeated dose. Minimum dosing interval is 4 hours. No
dose adjustment is necessary when converting from oral to IV dosing.
Care must be taken to avoid dosing errors, which could result in accidental overdose and death. In
particular, be careful to ensure that:
• Dose in milligrams and milliliters is not confused
• Dosing is based on weight for patients under 50 kg
• Infusion pump is programmed properly
• Total daily dose of acetaminophen from all sources (i.e., all routes [IV, oral, and rectal]) and all
acetaminophen-containing products does not exceed maximum daily limits.

Summary of Acetaminophen Dosing in Adults and Adolescents

Maximum Total Daily
Dose Given Dose Given Maximum Dose of Acetaminophen
Age-Group q 4 hr q 6 hr Single Dose (By All Routes)
Adults and adolescents 650 mg 1,000 mg 1,000 mg 4,000 mg in 24 hr
(13 years and older)
weighing $50 kg
Adults and adolescents 12.5 mg/kg 15 mg/kg 15 mg/kg (up 75 mg/kg in 24 hr (up to
(13 years and older) to 750 mg) 3,750 mg)
weighing ,50 kg

PEDIATRIC DOSE
See comments under Usual Dose.
Management of pain and reduction of fever in pediatric patients 2 to 12 years of age: 1
 5 mg/kg
every 6 hours or 12.5 mg/kg every 4 hours. Do not exceed a maximum single dose of
15 mg/kg or a maximum daily dose of 75 mg/kg/day. Minimum dosing interval is
4 hours.
Reduction of fever in infants 29 days to 2 years of age: 1
 5 mg/kg every 6 hours to a maximum
daily dose of acetaminophen 60 mg/kg/day, with a minimum dosing interval of 6 hours.
 ACETAMINOPHEN 9
Reduction of fever in neonates, including premature neonates born at 32 weeks or more gesta-
tional age, up to 28 days chronologic age: 12.5 mg/kg every 6 hours, to a maximum daily
dose of acetaminophen of 50 mg/kg/day, with a minimum dosing interval of 6 hours.
DOSE ADJUSTMENTS
A reduced total daily dose of acetaminophen may be appropriate in patients with hepatic
impairment or active liver disease. n A reduced total daily dose and longer dosing inter-
vals may be appropriate in patients with a CrCl less than or equal to 30 mL/min.
DILUTION
Available in a single-use vial or bag containing 1,000 mg/100 mL (10 mg/mL) of
­acetaminophen. For adults and adolescent patients weighing 50 kg or more requiring a
1,000-mg dose, administer the dose by inserting a vented IV set through the septum of
the 100-mL vial or a nonvented IV set through the administration spike port of the
­100-mL bag. Doses less than 1,000 mg should be withdrawn from the container and
placed into a separate empty container before administration to avoid inadvertent admin-
istration of an overdose. Withdraw appropriate dose (650 mg or weight-based) from
100-mL vial or bag and place in an empty container (e.g., syringe, glass bottle, plastic
IV container) for IV infusion.
Filter: I nformation not available.
Storage: Store unopened vial or bag at CRT. Do not refrigerate or freeze. Do not remove
bag from overwrap until ready to use. After removing the outer wrap, check the container
for minute leaks by squeezing the solution bag firmly. Discard 6 hours after entry into
the container or transfer into an empty container. Single-use product. Discard any unused
solution.
COMPATIBILITY
Manufacturer states, “Do not add other medications to solution. Incompatible with diaz-
epam and chlorpromazine. Do not administer simultaneously.”
Other sources suggest specific compatibilities dependent on concentration and manu-
facturer; consult a pharmacist.
RATE OF ADMINISTRATION
Administer as an infusion, equally distributed over 15 minutes. Pediatric doses up to
600 mg may be drawn up into a syringe and delivered via a syringe pump.
ACTIONS
A nonsalicylate antipyretic and a nonopioid analgesic agent. Exact mechanism of action
is unknown but is thought to act through central actions. Widely distributed into most
tissues except fat. Low protein binding (10% to 25%). Half-life is approximately 2 to
3 hours. Metabolized in the liver via three different pathways. Metabolites excreted in the
urine.
INDICATIONS AND USES
Management of mild to moderate pain in adults and pediatric patients 2 years of age and
older. n Management of moderate to severe pain with adjunctive opioid analgesics in
adults and pediatric patients 2 years of age and older. n Reduction of fever in adults and
pediatric patients.
CONTRAINDICATIONS
Known hypersensitivity to acetaminophen or to any components of the IV formula-
tion. n Patients with severe hepatic impairment or severe active liver disease.
PRECAUTIONS
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant
and death. Most cases of liver injury are associated with the use of acetaminophen at doses that exceed
the maximum daily limits and often involve more than one acetaminophen-containing product. Do not
exceed the maximum recommended daily dose. n Use with caution in patients with hepatic
impairment or active h­ epatic disease, alcoholism, chronic malnutrition, severe hypovole-
mia (e.g., due to d­ ehydration or blood loss), or severe renal impairment (CrCl less than
or equal to 30 mL/min). n Serious, sometimes fatal, skin reactions such as acute gener-
alized exanthematous pustulosis, Stevens-Johnson syndrome, and toxic epidermal
necrolysis have been reported rarely. n Hypersensitivity and anaphylactic reactions have
10 ACETAMINOPHEN

been reported. n Care must be taken when prescribing, preparing, or administering acet-
aminophen to avoid dosing errors, which could result in accidental overdose and death;
see Usual Dose. n Antipyretic effects may mask fever in patients treated for postsurgical
pain.
Monitor: B aseline SCr and liver function tests may be indicated. n Monitor for S/S of
hypersensitivity reaction (e.g., pruritus; rash; respiratory distress; swelling of the face,
mouth, and throat; urticaria). n Monitor for S/S of serious skin reactions.
Maternal/Child: E pidemiologic studies on oral acetaminophen use in pregnant women have
not reported a clear association between acetaminophen use and birth defects, miscar-
riage, or adverse maternal or fetal outcomes. Safety of IV formulation for use in preg-
nancy not established. Use only if clearly needed. n Safety for use in breast-feeding not
established. Acetaminophen is secreted in human milk in small quantities after oral ad-
ministration. Use caution. n The effectiveness for treatment of acute pain has not been
established in pediatric patients less than 2 years of age. n The safety and effectiveness
for treatment of fever in pediatric patients, including premature neonates born at
32 weeks or more gestational age, is supported by adequate and well-controlled studies.
Elderly: N
 o overall differences in safety and efficacy were observed between older and
younger patients, but greater sensitivity of some older individuals cannot be ruled out.
DRUG/LAB INTERACTIONS
Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 (e.g., ethanol, isonia-
zid) may alter the metabolism of acetaminophen and increase its hepatotoxic potential.
Effects have not been studied. n Ethanol may induce hepatic cytochromes but may also
act as a competitive inhibitor of the metabolism of acetaminophen. n Chronic acet-
aminophen doses of 4,000 mg/day may cause an increase in INR in patients stabilized on
warfarin. Effect of short-term use on INR has not been studied. Monitoring of INR recom-
mended. n Many available analgesics contain acetaminophen in combination with another
analgesic (e.g., hydrocodone/acetaminophen [Vicodin, Norco], oxycodone/­acetaminophen
[Percocet]). Over-the-counter cold and allergy preparations and sleep aids may also contain
acetaminophen in combination with other active ingredients. Monitor total daily dose of
acetaminophen coming from all possible sources.
SIDE EFFECTS
 he most common adverse reactions were headache, insomnia, nausea, and
Adult patients: T
vomiting. Less frequently reported side effects included anemia, anxiety, dyspnea,
­fatigue, fever, hypersensitivity reactions including anaphylaxis, hypertension, hypokale-
mia, hypotension, increased aspartate aminotransferase, infusion site pain, muscle
spasms, peripheral edema, and trismus.
Pediatric patients: T
 he most common adverse reactions were constipation, nausea, pru­
ritus, and vomiting. Less commonly reported side effects included abdominal pain,
­agitation, anemia, atelectasis, diarrhea, fever, headache, hypersensitivity reaction, hyper-
tension, hypervolemia, hypoalbuminemia, hypokalemia, hypomagnesemia, hypophos-
phatemia, hypotension, injection site pain, muscle spasm, oliguria, pleural effusion,
pulmonary edema, stridor, and wheezing.
Overdose: Early symptoms may include diaphoresis, general malaise, nausea, and vomit-
ing. More serious adverse effects include hepatic necrosis, renal tubular necrosis, hypo-
glycemic coma, and thrombocytopenia.
ANTIDOTE
Notify the physician of significant side effects. Discontinue immediately at the first ap-
pearance of skin rash or any other sign of hypersensitivity. Treat as indicated (e.g., di-
phenhydramine, epinephrine, albuterol). Resuscitate as necessary. If an acetaminophen
overdose is suspected, obtain a serum acetaminophen level and baseline liver function
studies. N-­acetylcysteine antidote may be indicated. See acetylcysteine monograph. Con-
tact a regional poison control center for additional information.
 11

ACETAZOLAMIDE SODIUM Antiglaucoma

(ah-set-ah-ZOE-la-myd SO-dee-um) Anticonvulsant
Diuretic
Urinary alkalinizer

Diamox pH 9.2

USUAL DOSE
Pretreatment: Baseline studies indicated; see Monitor.
Antiglaucoma agent: 2 50 mg to 1 Gm/24 hr. May be given as 250-mg doses at 4- to 6-hour
intervals. In the treatment of secondary glaucoma and in the preoperative treatment of
some cases of acute congestive (closed-angle) glaucoma, the preferred dose is 250 mg
every 4 hours. In acute cases, to rapidly lower intraocular pressure, an initial single dose
of 500 mg followed by 125 to 250 mg at 4-hour intervals may be given.
Edema of congestive heart failure or drug therapy: 2  50 to 375 mg or 5 mg/kg of body weight
as a single dose daily; when loss of edematous fluid stops, reduce to every other day or
give for 2 days followed by a day of rest.
Anticonvulsant: A  dults and pediatric patients: D  ose in epilepsy may range from 8 to
30 mg/kg/24 hr in divided doses every 6 to 12 hours (2 to 7.5 mg/kg every 6 hours or
4 to 15 mg/kg every 12 hours). Reduce initial daily dose when given with other
­anticonvulsants.
Urinary alkalinization: A
 dults and pediatric patients: 5
 mg/kg/dose every 8 to 12 hours.
PEDIATRIC DOSE
See Maternal/Child.
Acute antiglaucoma agent: 5
 to 10 mg/kg every 6 hours. Do not exceed 1,000 mg/24 hr.
Edema of congestive heart failure or drug therapy: 5 mg/kg as a single dose daily or every
other day; see comment under Usual Dose. Do not exceed 1,000 mg/24 hr.
Slowly progressive hydrocephalus in infants 2 weeks to 10 months (unlabeled): 2
 0 mg/kg/24 hr
in equally divided doses every 8 hours (8.3 mg/kg every 8 hours). Up to 100 mg/kg/24 hr
or a maximum dose of 2 Gm/24 hr has been used.
DOSE ADJUSTMENTS
Reduced dose required when introducing acetazolamide into a treatment regimen with
other anticonvulsants. n Administer every 12 hours in patients with a CrCl from 10 to
50 mL/min. Avoid use in patients with a CrCl less than 10 mL/min (ineffective).
DILUTION
Each 500 mg should be diluted in 5 mL SWFI. May then be given by IV injection or
added to standard IV fluids. IM administration not recommended.
Storage: R
 econstituted solution stable for 12 hours at RT or 3 days refrigerated.
COMPATIBILITY
Compatibility information not available from manufacturer.
Other sources suggest a few specific compatibilities dependent on concentration and
manufacturer; consult a pharmacist.
RATE OF ADMINISTRATION
500 mg or fraction thereof over at least 1 minute or added to IV fluids to be given over
4 to 8 hours.
ACTIONS
A potent carbonic anhydrase inhibitor and nonbacteriostatic sulfonamide, acetazolamide
depresses the tubular reabsorption of sodium, potassium, and bicarbonate. Excreted un-
changed in the urine, producing diuresis, alkalinization of the urine, and a mild degree of
metabolic acidosis.
12 ACETAZOLAMIDE SODIUM

INDICATIONS AND USES

Adjunctive treatment of edema due to congestive heart failure, drug-induced edema,
centrencephalic epilepsies (petit mal, unlocalized seizures), chronic simple (open-angle)
glaucoma, and secondary glaucoma, and preoperatively in acute angle-closure glaucoma
when delay of surgery is desired to lower intraocular pressure. n Used orally for acute
mountain ­sickness.
Unlabeled uses: M
 etabolic alkalosis, urine alkalinization, respiratory stimulant in COPD.
CONTRAINDICATIONS
Depressed sodium and potassium levels, hyperchloremic acidosis, marked kidney or liver
disease, adrenocortical insufficiency, hypersensitivity to acetazolamide or any of its com-
ponents. Long-term use contraindicated in some glaucomas.
PRECAUTIONS
Chemically related to sulfonamides; may cause serious reactions in sensitive pa-
tients. n May be alternated with other diuretics to achieve maximum effect. n Greater
diuretic action is achieved by skipping a day of treatment rather than increasing dose;
failure in therapy may be due to overdose or too-frequent dosage. n IM administration
not recommended. Administration by IV injection is preferred. n Use with caution in
impaired respiratory function (e.g., pulmonary disease, edema, infection, obstruction);
may cause severe respiratory acidosis. n Potassium excretion is proportional to diuresis.
Hypokalemia may result from diuresis or with severe cirrhosis. n Introduce or withdraw
gradually when used as an anticonvulsant.
Monitor: Obtain baseline CBC and platelet count before use and monitor during ther-
apy. n Periodic monitoring of electrolytes is recommended.
Patient Education: C
 onsider birth control options.
Maternal/Child: C
 ategory C: has been shown to be teratogenic in animal studies. Use dur-
ing pregnancy only if potential benefit justifies potential risks to the fetus. n Discontinue
breast-feeding or discontinue acetazolamide. n Safety for use in pediatric patients not
established, but no problems are documented.
Elderly: Use caution; no documented problems, but age-related renal impairment may be
a factor.
DRUG/LAB INTERACTIONS
May cause hypokalemia with concurrent use of steroids. n Hypokalemia may cause
toxicity and fatal cardiac arrhythmias with digoxin or interfere with insulin or oral antidia-
betic agent response, thus causing hyperglycemia. n Alkalinization of urine potentiates
amphetamines, ephedrine, flecainide (Tambocor), methenamine, procainamide, pseudoephed-
rine (Sudafed), quinidine, and tricyclic antidepressants (e.g., amitriptyline [Elavil]) by de-
creasing rate of excretion. n May decrease response to lithium, methotrexate, some antide-
pressants, phenobarbital, salicylates, and urinary anti-infectives by increasing rate of
excretion. n Metabolic acidosis induced by acetazolamide may potentiate salicylate
toxicity (anorexia, tachypnea, lethargy, coma, and death can occur with high-dose
­aspirin). n Alkalinity may cause false-positive urinary protein and possibly urinary steroid
tests. n May depress iodine uptake by the thyroid.
SIDE EFFECTS
Minimal with short-term therapy. Respond to symptomatic treatment or withdrawal of
drug: acidosis, anorexia, bone marrow suppression, confusion, crystalluria, drowsiness,
fever, hemolytic anemia, hypokalemia (ECG changes, fatigue, muscle weakness, vomit-
ing), paresthesias, photosensitivity, polyuria, rash, renal calculus, thrombocytopenic
purpura.
ANTIDOTE
Notify physician of any adverse effects and discontinue drug if necessary. Treat hyper-
sensitivity reactions as indicated; may require epinephrine, airway management, oxygen,
IV fluids, antihistamines (e.g., diphenhydramine [Benadryl]), corticosteroids (e.g., hy-
drocortisone sodium succinate [Solu-Cortef]), and pressor amines (e.g., dopamine).
Moderately dialyzable (20% to 40%).
 13

ACETYLCYSTEINE INJECTION Antidote

(ah-see-till-SIS-tay-een in-JEK-shun)

Acetadote pH 6 to 7.5

USUAL DOSE (ADULT AND PEDIATRIC)

Pretreatment assessment and testing after acute acetaminophen ingestion:
• Assess the history and timing of acetaminophen ingestion as an overdose. (The re-
ported history of the quantity ingested is often inaccurate and is not a reliable guide
to therapy.)
• Obtain baseline AST, ALT, bilirubin, INR, SCr, BUN, blood glucose, and electrolytes
to monitor hepatic and renal function and fluid and electrolyte balance.
• Obtain a plasma or serum sample to assay for acetaminophen concentration at least
4 hours after ingestion. (Levels obtained earlier than 4 hours postingestion may not
represent maximum acetaminophen concentration.)
• If the time of the acute acetaminophen ingestion is unknown, administer the loading
dose of acetylcysteine immediately and obtain an acetaminophen concentration to
determine the need for continued treatment.
• If the acetaminophen concentration cannot be obtained (or is unavailable or uninter-
pretable) within the 8-hour time interval after acetaminophen ingestion or if there is
clinical evidence of acetaminophen toxicity, administer a loading dose of acetylcyste-
ine immediately and continue treatment for a total of 3 doses over 21 hours.
• If the patient presents more than 8 hours after ingestion and the time of acute acet-
aminophen ingestion is known, administer a loading dose of acetylcysteine immedi-
ately and obtain an acetaminophen concentration to determine the need for continued
treatment.
• If the patient presents less than 8 hours after ingestion and both the time of acute
acetaminophen ingestion and the acetaminophen concentration are known, use the
Rumack-Matthew nomogram to determine whether to initiate treatment with acetyl-
cysteine. Initiation depends on acetaminophen concentration and on the clinical pre-
sentation of the patient.
Nomogram for estimating the potential for hepatotoxicity from acute acetaminophen ingestion
and the need for acetylcysteine treatment (see prescribing information for nomogram): A
 dmin-
ister a loading dose to the following patients:
• Patients whose acetaminophen concentrations are at or above the “possible” toxicity
line (dotted line in the nomogram)
• Patients with an acute overdose from an extended-release acetaminophen preparation
whose second acetaminophen concentrations (8 to 10 hours postingestion) are at or
above the “possible” toxicity line
• Patients whose values are below the “possible” toxicity line, but time of ingestion is
unknown or sample was obtained less than 4 hours after ingestion
Continue acetylcysteine treatment (with a maintenance dose [total of 3 separate doses
over 21 hours]) in the following patients:
• Patients whose acetaminophen concentrations are above the “possible” toxicity line
in the nomogram.
• Patients in whom an acetaminophen concentration could not be obtained.
• Patients whose values are below the “possible” toxicity line, but time of ingestion is
unknown or sample was obtained less than 4 hours after ingestion. Obtain a second
concentration and consider clinical status. If there is any uncertainty regarding pa-
tient’s risk of developing hepatotoxicity, it is recommended to administer a complete
treatment course.
Continued
14 ACETYLCYSTEINE INJECTION

Recommended dosage in adults and pediatric patients with acute acetaminophen ingestion:
Total dose equals 300 mg/kg given as 3 separate, sequential doses (i.e., 3-bag method to
administer the loading, second, and third doses). The total recommended infusion time
for the 3 doses is 21 hours. Total volume administered for patients less than 40 kg and
for those requiring fluid restriction can be adjusted as clinically needed; see the following
dosage charts for patients who weigh from 5 to 20 kg, from 21 to 40 kg, and for patients
weighing 41 kg or greater. Consider osmolarity; see Dilution and Precautions.
Distribute doses as indicated in the following guidelines:
Dosage for patients who weigh 5 to 20 kg:
Loading dose: 1  50 mg/kg diluted in 3 mL/kg of diluent administered over 1 hour.
Second dose: 5  0 mg/kg diluted in 7 mL/kg of diluent administered over 4 hours.
Third dose: 1
 00 mg/kg diluted in 14 mL/kg of diluent administered over 16 hours.

Acetylcysteine Dosage Guide by Weight in Patients 5 to 20 kg

Body Loading Dose: 150 mg/kg Second Dose: 50 mg/kg Third Dose: 100 mg/kg diluted
Weight diluted in 3 mL/kg of diluent diluted in 7 mL/kg of diluent in 14 mL/kg of diluent
(kg) administered over 1 hour administered over 4 hours administered over 16 hours
Loading Dose Diluent Second Dose Diluent Third Dose Diluent
(mg) Volume (mL) (mg) Volume (mL) (mg) Volume (mL)
5 kga 750 mg 15 mL 250 mg 35 mL 500 mg 70 mL
10 kg 1,500 mg 30 mL 500 mg 70 mL 1,000 mg 140 mL
15 kg 2,250 mg 45 mL 750 mg 105 mL 1,500 mg 210 mL
20 kg 3,000 mg 60 mL 1,000 mg 140 mL 2,000 mg 280 mL
a
Recommended dosage for patients less than 5 kg has not been studied.

Dosage for patients who weigh 21 to 40 kg:

Loading dose: 1  50 mg/kg diluted in 100 mL of diluent administered over 1 hour.
Second dose: 5  0 mg/kg diluted in 250 mL of diluent administered over 4 hours.
Third dose: 1
 00 mg/kg diluted in 500 mL of diluent administered over 16 hours.

Acetylcysteine Dosage Guide by Weight in Patients 21 to 40 kg

Body Weight Loading Dose: 150 mg/kg Second Dose: 50 mg/kg in Third Dose: 100 mg/kg in
(kg) in 100 mL of diluent 250 mL of diluent 500 mL of diluent
administered over 1 hour administered over 4 hours administered over 16 hours
Total Acetylcysteine Dose Total Acetylcysteine Dose Total Acetylcysteine Dose
(mg) (mg) (mg)
21 kg 3,150 mg 1,050 mg 2,100 mg
30 kg 4,500 mg 1,500 mg 3,000 mg
40 kg 6,000 mg 2,000 mg 4,000 mg

Dosage for patients who weigh 41 kg or greater:

Loading dose: 1  50 mg/kg diluted in 200 mL of diluent administered over 1 hour.
Second dose: 5  0 mg/kg diluted in 500 mL of diluent administered over 4 hours.
Third dose: 1
 00 mg/kg diluted in 1,000 mL of diluent administered over 16 hours.
 ACETYLCYSTEINE INJECTION 15

Acetylcysteine Dosage Guide by Weight in Patients 41 kg or Greater

Body Weight Loading Dose: 150 mg/kg in Second Dose: 50 mg/kg in Third Dose: 100 mg/kg in
(kg) 200 mL of diluent 500 mL of diluent 1,000 mL of diluent
administered over 1 hour administered over 4 hours administered over 16 hours
Total Acetylcysteine Dose Total Acetylcysteine Dose Total Acetylcysteine Dose
(mg) (mg) (mg)
41 kg 6,150 mg 2,050 mg 4,100 mg
50 kg 7,500 mg 2,500 mg 5,000 mg
60 kg 9,000 mg 3,000 mg 6,000 mg
70 kg 10,500 mg 3,500 mg 7,000 mg
80 kg 12,000 mg 4,000 mg 8,000 mg
90 kg 13,500 mg 4,500 mg 9,000 mg
$100 kga 15,000 mg 5,000 mg 10,000 mg
a
No specific studies have been done to evaluate the necessity of dose adjustments in patients weighing over 100 kg. Lim-
ited information is available regarding the dosage requirements of patients who weigh more than 100 kg.

DOSE ADJUSTMENTS
Therapy extending beyond 21 hours may be considered in rare cases such as suspected
massive overdose, concomitant ingestion of other substances, or in patients with pre-
existing liver disease. In these cases, absorption and/or half-life of acetaminophen may
be prolonged. Obtain acetaminophen levels and ALT/AST and INR before the end of
the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which
ALT/AST is still increasing or INR remains elevated, continue the infusion and contact
a regional poison control center. n Specific information and/or recommendations are not
available for patients with impaired hepatic or renal function.
DILUTION
Available in single-dose vials containing 6 Gm/30 mL. May be diluted in D5W, 1/ 2NS,
or SWFI. See Usual Dose for dilution guidelines based on weight. Total volume admin-
istered should be adjusted for patients less than 40 kg or for those requiring fluid restric-
tion. Hyponatremia and seizures may result from large volumes in small pediatric pa-
tients. n A hyperosmolar solution. Caution is advised when the diluent volume is
decreased; hyperosmolarity of the solution is increased as shown in the following chart.

Acetylcysteine Concentration and Osmolarity

Acetylcysteine Osmolarity in ½NS Osmolarity in D5W Osmolarity in SWFI
Concentration (mg/mL) (mOsmol/L) (mOsmol/L) (mOsmol/L)
7 mg/mL 245 mOsmol/L 343 mOsmol/L 91 mOsmol/La
24 mg/mL 466 mOsmol/L 564 mOsmol/L 312 mOsmol/L
a
Osmolarity should be adjusted to a physiologically safe level (generally not less than 150 mOsmol/L in pediatric patients).

Color of acetylcysteine may change from colorless to a slight pink or purple once the
stopper is punctured; quality is not affected.
Filters: D
 ata not available and use is not required by manufacturer.
Storage: S  tore unopened vials at CRT. Diluted solution is stable for 24 hours at CRT. Do
not use previously opened vials for IV administration. Discard unused portions.
COMPATIBILITY
Manufacturer states, “Compatible with D5W, 1/2NS, and SWFI.”
RATE OF ADMINISTRATION
Usual total infusion time of all 3 doses is 21 hours. Rate reduction may be required to
manage S/S of infusion reactions; see Monitor and Antidote.
16 ACETYLCYSTEINE INJECTION

Loading dose: A n infusion evenly distributed over 60 minutes.

Second dose: A n infusion evenly distributed over 4 hours.
Third dose: A
 n infusion evenly distributed over 16 hours.
ACTIONS
Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity.
Acetylcysteine is an antidote for acetaminophen overdose that protects the liver by main-
taining or restoring the glutathione levels (metabolites formed after an overdose of acet-
aminophen may deplete the hepatic stores of glutathione and cause binding of the me-
tabolite to protein molecules within the hepatocyte, resulting in cellular necrosis). It may
also act by forming an alternate substrate and detoxifying the reactive metabolite of
­acetaminophen. Acetylcysteine is postulated to form cysteine and disulfides. Cysteine is
further metabolized to form glutathione and other metabolites. Half-life is approximately
5.6 hours. Crosses the placental barrier. Some excretion in urine.
INDICATIONS AND USES
To prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity
of acetaminophen in patients with acute ingestion or repeated supratherapeutic ingestion
(RSI).
CONTRAINDICATIONS
Known hypersensitivity to acetylcysteine or any of its components.
PRECAUTIONS
For IV administration only. n Should be administered in a facility equipped to monitor
the patient and respond to any medical emergency. n Most effective against severe he-
patic injury when administered within 8 hours of ingestion. Administration before 4 hours
does not allow enough time to determine an actual need for treatment with acetylcysteine;
serum levels drawn before 4 hours have passed may be misleading. Effectiveness dimin-
ishes gradually after 8 hours. Should be administered if 24 hours or less has passed since
ingestion, because the reported time of ingestion may not be correct and it does not appear
to worsen the patient’s condition. n Total volume administered should be adjusted for
patients less than 40 kg and for patients requiring fluid restriction. If volume is not ad-
justed, fluid overload can occur, potentially resulting in hyponatremia, seizure, and death;
see Usual Dose. n Hypersensitivity reactions have been reported and usually occur soon
after initiation of the infusion. Use caution in patients with asthma or a history of bron-
chospasm. Death occurred in a patient with asthma. n Acute flushing and erythema of the
skin may occur. These reactions usually occur within 30 to 60 minutes of beginning the
infusion and often resolve spontaneously despite continued infusion. n Clearance de-
creased and half-life prolonged in patients with various stages of liver damage. n The
Rumack-Matthew nomogram does not apply to patients with repeated supratherapeutic
ingestion (RSI), which is defined as ingestion of acetaminophen at doses higher than those
recommended for extended periods of time. For treatment information, see prescribing
information for a professional assistance line for acetaminophen overdose, or contact a
regional poison control center. n The Rumack-Matthew nomogram may underestimate
the risk for hepatotoxicity in patients with chronic alcoholism, malnutrition, or CYP2E1
enzyme-inducing drugs (e.g., isoniazid [INH]). Consideration should be given to treating
these patients even if the acetaminophen concentrations are in the nontoxic range. n Vial
stopper does not contain natural rubber latex. n See Monitor and Antidote.
Monitor: O btain baseline AST, ALT, bilirubin, INR, SCr, BUN, blood glucose, and elec-
trolytes to monitor hepatic and renal function and electrolyte and fluid balance. Continue
monitoring as indicated.
Preferred method of treatment: Estimate time of acetaminophen ingestion. If less than 24
hours since overdose, draw an acetaminophen level at 4 hours postingestion or as soon
as possible thereafter to clarify the need for intervention with acetylcysteine. The serum
acetaminophen level should be evaluated on the Rumack-Matthew nomogram to deter-
mine the probability of toxicity (see package insert for copy of nomogram). n If serum
 ACETYLCYSTEINE INJECTION 17

acetaminophen level is below the treatment line on the nomogram, discontinue the acet-
ylcysteine if initiated as a precaution. If the plasma level is above the treatment line on
the nomogram, initiate or continue treatment.
Secondary options for treatment: I f serum acetaminophen levels are not available within 8
hours, initiate treatment. Do not delay treatment more than 8 hours postingestion. n If
time of ingestion is unknown or if the patient is unreliable, consider empiric initiation of
acetylcysteine treatment. n If a serum acetaminophen level is not available or cannot be
interpreted and less than 24 hours has elapsed since ingestion, administer acetylcysteine
regardless of the quantity reported to have been ingested.
All treatment options: Monitor vital signs before, during, and after the infusion. n Evalu-
ate serum acetaminophen level on the Rumack-Matthew nomogram. n Infusion reac-
tions may begin with acute flushing and erythema of the skin. May resolve spontaneously
despite continued infusion of acetylcysteine or may progress to an acute hypersensitivity
reaction and/or anaphylaxis. Observe continuously for initial S/S of a hypersensitivity
reaction (e.g., hypotension, rash, shortness of breath, wheezing). n In suspected toxicity
resulting from the extended-release acetaminophen preparation, an acetaminophen level
drawn fewer than 8 hours postingestion may be misleading. Draw a second level at 8 to
10 hours after the acute ingestion. If either acetaminophen level falls above the toxicity
line, acetylcysteine treatment should be initiated. n See Precautions and Antidote.
Patient Education: R
 eport S/S of hypersensitivity promptly (e.g., bronchospasm, hypoten-
sion, shortness of breath, wheezing).
Maternal/Child: Use during pregnancy only if clearly needed. Delaying treatment of acet-
aminophen overdose may increase the risk of maternal or fetal morbidity and mortal-
ity. n Use caution; safety for use during breast-feeding not established; effects unknown.
After 30 hours, acetylcysteine should be cleared from maternal blood, and breast-feeding
can be resumed. n No adequate or well-controlled studies in pediatric patients; use is
based on clinical practice. Efficacy appears to be similar to that seen in adults; see Side
Effects.
Elderly: D
 ifferences in response compared with younger adults not known.
DRUG/LAB INTERACTIONS
Drug-drug interaction studies have not been done.
SIDE EFFECTS
Adult and pediatric patients: Facial flushing, pruritus, rash, and urticaria have been reported
most frequently and most commonly occur during the initial loading dose. Other reported
side effects include edema, hypersensitivity reactions (including anaphylaxis), hypoten-
sion, nausea and vomiting, pharyngitis, respiratory symptoms (e.g., bronchospasm, chest
tightness, cough, respiratory distress, shortness of breath, stridor, wheezing), rhinorrhea,
rhonchi, tachycardia, and throat tightness.
Overdose: S  /S of acute toxicity in animals included ataxia, convulsions, cyanosis, hypo-
activity, labored respiration, and loss of righting reflex.
ANTIDOTE
Keep physician informed of all side effects. Flushing and erythema of the skin may occur
and often resolve spontaneously. If other symptoms of a hypersensitivity reaction occur
(e.g., bronchospasm, dyspnea, hypotension, wheezing), discontinue acetylcysteine and
treat with diphenhydra­mine (Benadryl) or epinephrine as indicated. After symptoms
subside, the infusion may be carefully resumed. If S/S of hypersensitivity recur, dis­
continue infusion permanently and consider alternate treatments. Contact a regional
poison control center for possible treatment alternatives. Hemodialysis may remove
some acetylcysteine.
18

ACYCLOVIR Antiviral
(ay-SYE-kloh-veer)

Zovirax pH 11

USUAL DOSE
Pretreatment: See Precautions and Monitor.
In all situations for adults, adolescents, children, and neonates, do not exceed a
maximum dose of 20 mg/kg every 8 hours.
Adults and adolescents (12 years of age and older):
Herpes simplex infections; mucosal and cutaneous HSV infections in immunocompromised
patients: 5
 mg/kg of body weight every 8 hours for 7 days.
Severe initial clinical episodes of herpes genitalis: 5
 mg/kg every 8 hours for 5 days.
Herpes simplex encephalitis: 1  0 mg/kg every 8 hours for 10 days.
Herpes zoster infections (shingles) in immunocompromised patients: 1  0 mg/kg every 8 hours
for 7 days.
PEDIATRIC DOSE
Herpes simplex infections; mucosal and cutaneous HSV infections in immunocompromised
patients: P
 ediatric patients 3 months to 12 years: 1
 0 mg/kg every 8 hours for 7 days.
Herpes simplex encephalitis: Pediatric patients 3 months to 12 years: 20 mg/kg every 8 hours
for 10 days.
Herpes zoster infections (shingles) in immunocompromised patients: P  ediatric patients under
12 years: 2
 0 mg/kg every 8 hours for 7 days.
NEONATAL DOSE
Neonatal herpes simplex virus infections: PMA of at least 34 weeks: 20 mg/kg every 8 hours
for 21 days.
PMA of less than 34 weeks: 2
 0 mg/kg every 12 hours for 21 days.
Doses recommended should be used with caution in neonates with ongoing medical
conditions affecting their renal function beyond the effect of prematurity.
DOSE ADJUSTMENTS
Calculate dose by ideal body weight in obese individuals. n Reduced dose may be indi-
cated in the elderly based on the potential for decreased renal function and concomitant
disease or drug therapy. n In adults and pediatric patients (older than 3 months) with
impaired renal function, reduce dose and/or adjust dosing interval based on CrCl as in-
dicated in the following chart.

Acyclovir Dosage Adjustments for Adults and Pediatric Patients With Renal Impairment
Creatinine Clearance
(mL/min per 1.73 M2) Percent of Recommended Dose Dosing Interval (hours)
.50 mL/min 100% Every 8 hr
$25-50 mL/min 100% Every 12 hr
$10-25 mL/min 100% Every 24 hr
#0-10 mL/min 50% Every 24 hr

Plasma concentrations decrease with hemodialysis; adjustment of the dosing schedule is

recommended so that an additional dose is administered after each dialysis. No supple-
mental dose is indicated in peritoneal dialysis after adjustment of the dosing interval.
DILUTION
Initially dissolve each 500 mg with 10 mL SWFI (1,000 mg with 20 mL). Concentration
equals 50 mg/mL. Do not use bacteriostatic water for injection (BWFI); will cause pre-
cipitation. Shake well to dissolve completely. Also available in liquid vials. Withdraw the
Another random document with
no related content on Scribd:
 Fig. 30.—Didymium difforme. A, two sporangia (spg 1 and 2) on a fragment of
leaf (l); B, section of sporangium, with ruptured outer layer (a), and threads
of capillitium (cp); C, a flagellula with contractile vacuole (c.vac) and
nucleus (nu); D, the same after loss of flagellum; b, an ingested bacillus; E,
an amoebula; F, conjugation of amoebulae to form a small plasmodium; G,
a larger plasmodium accompanied by numerous amoebulae; sp, ingested
spores. (After Lister.)

Again, in some cases the plasmodia themselves aggregate in the

same way as the amoeboids do in the Acrasieae, and combine to
form a compound fruit termed an "aethalium,"[98] with the regions of
the separate plasmodia more or less clearly marked off. The species
formerly termed Aethalium septicum is now known as Fuligo varians.
It is a large and conspicuous species, common on tan, and is a pest
in the tanpits. Its aethalia may reach a diameter of a foot and more,
and a thickness of two inches. Chondrioderma diffusum, often
utilised as a convenient "laboratory type," is common on the
decaying haulms of beans in the late autumn. The interest of this
group is entirely biological, save for the "flowers of tan."[99]

CHAPTER IV
 PROTOZOA (CONTINUED): SPOROZOA[100]

II. Sporozoa.
Protozoa parasitic in Metazoa, usually intracellular for at least part of their
cycle, rarely possessing pseudopodia, or flagella (save in the sperms), never
cilia; reproduction by brood-formation, often of alternating types; syngamy
leading up to resting spores in which minute sickle-germs are formed, or
unknown (Myxosporidiaceae).

This group, of which seven years ago no single species was known
in its complete cycle, has recently become the subject of
concentrated and successful study, owing to the fact that it has been
recognised to contain the organisms which induce such scourges to
animals as malarial fevers, and various destructive murrains. Our
earliest accurate, if partial knowledge, was due to von Siebold,
Kölliker, and van Beneden. Thirty years ago Ray Lankester in
England commenced the study of species that dwell in the blood,
destined to be of such moment for the well-being of man and the
animals in his service; and since then our knowledge has increased
by the labours of Manson, Ross and Minchin at home, Laveran,
Blanchard, Thélohan, Léger, Cuénot, Mesnil, Aimé Schneider in
France, Grassi in Italy, Schaudinn, Siedlecki, L. and R. Pfeiffer,
Doflein in Central Europe, and many others.
 Fig. 31.—Lankesteria ascidiae, showing life-cycle. a, b, c, Sporozoites in
digestive epithelium cells of host; d, e, growth stages; f, free gregarine; g,
association; h, encystment; i, j, brood-divisions in associated mates; k,
pairing-cells; l, syngamy; m, zygote; n, o, p, nuclear divisions in spores; q,
cyst with adult spores, each containing 8 sickle-germs. (After Luhe,
modified from Siedlecki.)

As a type we will take a simple form of the highest group, the

Gregarinidaceae, Monocystis, which inhabits the seminal vesicles of
the earthworm. In its youngest state, the "sporozoite," it is a naked,
sickle-shaped cell, which probably makes its way from the gut into
one of the large radial cells of the seminal funnel, where it attains its
full size, and then passes out into the vesicles or reservoirs of the
semen, to lie among the sperm morulae and young spermatozoa.
The whole interior is formed of the opaque endosarc, which contains
a large central nucleus, and is full of refractive granules of
paramylum or paraglycogen,[101] a carbohydrate allied to glycogen
or animal starch, so common in the liver and muscles of Metazoa;
besides these it contains proteid granules which stain with carmine,
and oil-drops. The ectosarc is formed of three layers: (1) the outer
layer or "cuticle"[102] is, in many cases if not here, ribbed, with
minute pores in the furrows, and is always porous enough to allow
the diffusion of dissolved nutriment; (2) a clear plasmatic layer, the
"sarcocyte"; (3) the "myocyte," formed of "myonemes," muscular
fibrils disposed in a network with transverse meshes, which effect
the wriggling movements of the cell. The endosarc contains the
granules and the large central nucleus. The adult becomes free in
the seminal vesicles; here two approximate, and surround
themselves with a common cyst: a process which has received the
name of "association" (Fig. 31, g-i). Within this, however, the
protoplasms remain absolutely distinct. The nucleus undergoes
peculiar changes by which its volume is considerably reduced. When
this process of "nuclear reduction" is completed, each of the mates
undergoes brood-divisions (j), so as to give rise to a large number of
rounded naked 1-nucleate cells—the true pairing-cells. These unite
two and two, and so form the 1-nucleate spores (k-m), which
become oat-shaped, form a dense cyst-wall, and have been termed
"pseudonavicellae" from their likeness to the Diatomaceous genus
Navicella. Some of the cytoplasm of the original cells remains over
unused, as "epiplasm," and ultimately degenerates, as do a certain
number of the brood-cells which presumably have failed to pair. It is
believed that the brood-cells from the same parent will not unite
together. The contents of each spore have again undergone brood-
division to form eight sickle-shaped zoospores, or "sporozoites" (n-
q), and thus the developmental cycle is completed. Probably the
spores, swallowed by birds, pass out in their excrement, and when
eaten by an earthworm open in its gut; the freed sickle-germs can
now migrate through the tissues to the seminal funnels, in the cells
of which they grow, ultimately becoming free in the seminal vesicles.
[103]

We may now pass to the classification of the group.

A. Telosporidia.—Cells 1-nucleate until the onset of brood-

formation, which is simultaneous.
1. Gregarinidaceae.—Cells early provided with a firm
pellicle and possessing a complex ectosarc; at first
intracellular, soon becoming free in the gut or coelom of
Invertebrates. Pairing between adults, which
simultaneously produce each its brood of gametes,
isogamous or bisexual, which pair within the common
cyst; zygotospores surrounded by a firm cyst, and
producing within a brood of sickle-shaped zoospores.
(i.) Schizogregarinidae.—Multiplying by simple
fission in the free state as well as by brood-
formation; the brood-cells conjugating in a common
cyst, but producing only one pairing nucleus in
each mate (the rest aborting), and consequently
only one spore.
Ophryocystis A. Schn.
(ii.) Acephalinidae.—Cell one-chambered, usually
 without an epimerite for attachment.
Monocystis F. Stein; Lankesteria Mingazzini.
(iii.) Dicystidae.—Cell divided by a plasmic partition;
epimerite usually present.
Gregarina Dufour; Stylorhynchus A. Schn.;
Pterocephalus A. Schn.
2. Coccidiaceae.—Cells of simple structure, intracellular in
Metazoa. Pairing between isolated cells usually
sexually differentiated as oosphere and sperm, the
latter often flagellate. Brood-formation of the adult cell
giving rise to sickle-shaped zoospores (merozoites), or
progamic and producing the gametes. Oosperm motile
or motionless, finally producing a brood of spores,
which again give rise to a brood of sickle-spores.
(i.) Coccidiidae.—Cell permanently intracellular, or
very rarely coelomic, encysting or not before
division; zoospores always sickle-shaped; oosperm
encysting at once, producing spores with a dense
cell-wall producing sickle-germs.
(ii.) Haemosporidae.—Cells parasitic in the blood
corpuscles or free in the blood of cold-blooded
animals, encysting before brood-formation;
zoospores sickle-shaped; oosperm at first motile.
Lankesterella Labbé; (Drepanidium Lank.;)
Karyolysus Labbé; Haemogregarina Danilewski.
(iii.) Acystosporidae.—Cells parasitic in the blood and
haematocytes of warm-blooded Vertebrates; never
forming a cyst-wall before dividing; zoospores
formed in the corpuscles, amoeboid. Gametocytes
only forming gametes when taken into the stomach
of insects. Oosperm at first active, passing into the
coelom, producing naked spores which again
produce a large brood of sickle zoospores, which
 migrate to the salivary gland, and are injected with
the saliva into the warm-blooded host.
Haemamoeba Grassi and Feletti; Laverania Grassi
and Feletti; Haemoproteus Kruse; Halteridium Labbé.
[104]

B. Neosporidia.—Cells becoming multinucleate apocytes

before any brood-formation occurs. Brood-formation
progressive through the apocyte, not simultaneous.
1. Myxosporidiaceae.—Naked parasites in cold-blooded
animals. Spore-formation due to an aggregation of
cytoplasm around a single nucleus to form an
archespore, which then produces a complex of cells
within which two daughter-cells form the spores and
accessory nematocysts.
Myxidium Bütsch.; Myxobolus Bütsch.; Henneguya
Thélohan; Nosema Nageli (= Glugea Th.).
2. Actinomyxidiaceae.[105]—Apocyte resolved into a
sporange, containing eight secondary sporanges (so-
called spores), of ternary symmetry and provided with
three polar nematocysts.
3. Sarcosporidiaceae.—Encysted parasites in the
muscles of Vertebrates, with a double membrane;
spores simple.
Sarcocystis Lankester.

Fig. 32.—Gregarina blattarum Sieb. A, two cephalonts, embedded by their

epimerite (ep), in cells of the gut-epithelium; deu, deutomerite; nu, nucleus;
 pr, protomerite; B1, B2, two free specimens of an allied genus; the epimerite
is falling off in B2, which is on its way to become a sporont; C, cyst (cy) of A,
with sporoducts (spd) discharging the spores (sp), surrounded by an
external gelatinous investment (g). (From Parker and Haswell.)

Monocystis offers us the simplest type of Gregarinidaceae. In most

Gregarines (Figs. 31, 32) the sporozoite enters the epithelium-cell of
the gut of an Arthropod, Worm or Mollusc, and as it enlarges
protrudes the greater part of its bulk into the lumen, and may
become free therein, or pass into the coelom. The attached part is
often enlarged into a sort of grapple armed with spines, the
"epimerite"; this contains only sarcocyte, the other layers being
absent. The freely projecting body is usually divided by an ingrowth
of the myocyte into a front segment ("protomerite"), and a rear one
("deutomerite"), with the nucleus usually in the latter. In this state the
cell is termed a "cephalont." Conjugation is frequent, but apparently
is not always connected with syngamy or spore-formation;
sometimes from two to five may be aggregated into a chain or
"syzygy." The number of cases in which a syngamic process
between two cells has been observed is constantly being increased.
In Stylorhynchus (Fig. 33) the conjugation at first resembles that of
Monocystis, but the actual pairing-cells are bisexually differentiated
into sperms in the one parent, and oospheres in the other; it is
remarkable that here the pear-shaped sperms are apparently larger
than the oospheres. In Pterocephalus the chief difference is that the
sperms are minute.[106] In all cases of spore-formation the epimerite
is lost and the septum disappears; in this state the cell is termed a
sporont. Sometimes the epiplasm of the sporont forms tubes
("sporoducts"), which project through the cyst-wall and give exit to
the spores, as in Gregarina (Fig. 32, C), a parasite in the beetle
Blaps.

Gregarines infest most groups of Invertebrates except Sponges and

perhaps Coelenterates, the only exception cited being that of
Epizoanthus glacialis, a Zoantharian (p. 406). They appear to be
relatively harmless and are not known to induce epidemics.
The Coccidiaceae never attain so high a degree of cellular
differentiation as the Gregarines, which may be due to their habitat;
for in the growing state they are intracellular parasites. Their life-
history shows a double cycle, which has been most thoroughly
worked out in Coccidiidae by Schaudinn and Siedlecki in parasites
of our common Centipedes. We take that of Coccidium schubergi (in
Lithobius forficatus[107]), beginning with the sporozoite, which is
liberated from the spores taken in with the food, in the gut of the
Centipede. This active sickle-shaped cell (Fig. 34, l) enters an
epithelial cell of the mid-gut, and grows therein till it attains its full
size (a), when it is termed a "schizont"; for it segments (Gk. σχίζω, "I
split") superficially into a large number of sickle-shaped zoospores,
the "merozoites" (c), resembling the sporozoites. The segmentation
is superficial, so that there may remain a large mass of residual
epiplasm. The merozoites are set free by the destruction of the
epithelium-cell in which they were formed, and which becomes
disorganised, like the residual epiplasm. Each merozoite may repeat
the behaviour of the sporozoite, so that the disease spreads freely,
and becomes acute after several reinfections. After a time the adult
parasites, instead of becoming schizonts and simply forming
merozoites by division, differentiate into cells that undergo a binary
sexual differentiation. Some cells, the "oocytes" (d, e), escape into
the gut, and the nucleus undergoes changes by which some of its
substance (or an abortive daughter-nucleus) is expelled to the
exterior (f), such a cell is now an "oogamete" or oosphere. Others,
again, are spermatogones (h): each when full grown on escaping
into the gut commences a division (i, j), like that of the schizonts. The
products of this division or segment-cells are the flagellate sperms
(s): they are more numerous and more minute than the merozoites
produced by the schizonts, and are attracted to the oosphere by
chemiotaxy (p. 23), and one enters it and fuses with it (g). The
oosperm, zygote or fertilised egg, thus formed invests itself with a
dense cyst-wall, as a "oospore" (k), its contents form one or more (2,
4, 8, etc.) spores; and each spore forms again one, two, or four
sickle-shaped zoospores ("sporozoites"), destined to be liberated for
a fresh cycle of parasitic life when the spores are swallowed by
another host.
 Fig. 33.—Bisexual pairing of Stylorhynchus. a, Spermatozoon; b-e, fusion of
cytoplasm of spermatozoon and oosphere; f, g, fusion of nuclei; h-j,
development of wall to zygote; k, l, formation of four sporoblasts; l, side
view of spore; m, mature sporozoites in spore. (After Léger.)

Fig. 34.—Life-history of Coccidium schubergi. a, Penetration of epithelium-cell of

host by sporozoite; b-d, stages of multiple cell-formation in naked state
(schizogony); e, f, formation of oogamete; g, conjugation; h-j, formation of
sperms (s); k, development of zygote (fertilised ovum) to form four spores; l,
formation of two zoospores (or sickle germs) in each spore. (From Calkins's
Protozoa, after Schaudinn.)

In some cases the oogametes are at first oblong, like ordinary

merozoites, and round off in the gut. The microgametocyte, or
spermatogone, has the same character, but is smaller; it applies
itself like a cap to one pole of the oogamete, which has rounded off;
it then divides into four sperms, whose cytoplasm is not sharply
separated; one of these then separates from the common mass,
enters the oogamete, and so conjugation is effected, with an
oosperm as its result. This latter mode of conjugation is that of
Adelea ovata and Coccidium lacazei: the former is probably the
more primitive and the commoner. The sperms of Coccidiidae, when
free, usually possess two long flagella, either both anterior, or a very
long one in front and a short one behind, both turned backwards.

The genus Coccidium affects many animals, and one species in

particular, C. cuniculi Rivolta, attacks the liver of young rabbits,[108]
giving rise to the disease "coccidiosis." Coccidium may also produce
a sort of dysentery in cattle on the Alpine pastures of Switzerland;
and cases of human coccidiosis are by no means unknown.
Coccidium-like bodies have been demonstrated in the human
disease, "molluscum contagiosum," and the "oriental sore" of Asia;
similar bodies have also been recorded in smallpox and vaccinia,
malignant tumours and even syphilis, but their nature is not certainly
known; some of these are now referred to Flagellata (see p. 121).

Closely allied to the Coccidiidae are the Haemosporidae, dwellers

in the blood of various cold-blooded Vertebrates,[109] and entering
the corpuscles as sporozoites or merozoites to attain the full size,
when they divide by schizogony; they are freed like those of the next
family by the breaking up of the corpuscle. The merozoites were
described by Gaule (1879) as "vermicles" ("Würmchen"), and
regarded by him as peculiar segregation-products of the blood;
though Lankester had described the same species in the Frog's
blood as early as 1871, with a full recognition of its true character.
His name, Drepanidium, has had to give way, having been
appropriated to another animal, and has been aptly replaced by that
of Lankesterella. The sexual process of Karyolysus has been found
to take place in a Tick, that of Haemogregarina in a Leech, thus
presenting a close analogy to the next group, which only differs in its
less definite form in the active state, and in the lack of a cell-wall
during brood-formation.
Laveran was the first to describe a member of the Acystosporidae,
in 1880, as an organism always to be found in the blood of patients
suffering from malarial fever; this received the rather inappropriate
name of Plasmodium, which, by a pedantic adherence to the laws of
priority, has been used by systematists as a generic name. Golgi
demonstrated the coincidence of the stages of the intermittent fever
with those of the life-cycle of the parasite in the patient, the
maturation of the schizont and liberation of the sporozoites
coinciding with the fits of fever. Manson, who had already shown that
the Nematodes of the blood that give rise to Filarial haematuria (see
Vol. II. p. 149) have an alternating life in the gnats or mosquitos of
the common genus Culex,[110] in 1896 suggested to Ronald Ross
that the same might apply to this parasite, and thus inspired a most
successful work. The hypothesis had old prejudices in its favour, for
in many parts there was a current belief that sleeping under
mosquito-netting at least helped other precautions against malaria.
Ross found early in his investigations that Culex was a good host for
the allied genus Haemoproteus or Proteosoma, parasitic in birds, but
could neither inoculate man with fever nor be inoculated from man.
He found, however, that the malaria germs from man underwent
further changes in the stomach of a "dappled-wing mosquito," that is,
as we have since learned, a member of the genus Anopheles.
Thenceforward the study advanced rapidly, and a number of
inquirers, including Grassi, Koch, MacCallum (who discovered the
true method of sexual union in Halteridium[111]), and Ross himself,
completed his discovery by supplying a complete picture of the life-
cycles of the malaria-germs. Unfortunately, there has been a most
unhappy rivalry as to the priority of the share in each fragment of the
discovery, whose history is summarised by Nuttall, we believe, with
perfect fairness.[112]

The merozoite is always amoeboid, and in this state enters the blood
corpuscle; herein it attains its full size, as a schizont, becoming filled
with granules of "melanin" or black pigment, probably a
decomposition product of the red colouring matter (haemoglobin).
 Fig. 35.—Life-history of Malarial Parasites. A-G, Amoebula of quartan parasite to
sporulation; H, its gametocyte; I-M, amoebula of tertian parasite to
sporulation; N, its gametocyte; O, T, "crescents" or gametocytes of
Laverania; P-S, sperm-formation; U-W, maturation of oosphere; X,
fertilisation; Y, zygote. a, Zygote enlarging in gut of Mosquito; b-e, passing
into the coelom; f, the contents segmented into naked spores; g, the spores
forming sickle-germs or sporozoites; h, sporozoites passing into the salivary
glands. (From Calkins's Protozoa, after Ross and Fielding Ould.)

The nucleus of the schizont now divides repeatedly, and then the
schizont segments into a flat brood of germs (merozoites), relatively
few in the parasite of quartan fever (Haemamoeba malariae, Fig. 35,
E-G), many in that of tertian (H. vivax, Fig. 35, M). These brood-cells
escape and behave for the most part as before. But after the disease
has persisted for some time we find that in the genus Haemamoeba,
which induces the common malarial fevers of temperate regions,
certain of the full-grown germs, instead of behaving as schizonts,
pass, as it were, to rest as round cells; while in the allied genus
Laverania, (Haemomenas, Ross) these resting-cells are crescentic,
with blunt horns, and are usually termed half-moons (Fig. 35, O, T),
characteristic of the bilious or pernicious remittent fevers of the
tropics and of the warmer temperate regions in summer. These
round or crescent-shaped cells are the gametocytes, which only
develop further in the drawn blood, whether under the microscope,
protected against evaporation, or in the stomach of the Anopheles:
the crescents become round, and then they, like the already round
ones of Haemamoeba, differentiate in exactly the same way as the
corresponding cells of Coccidium schubergi. The female cell only
exhibits certain changes in its nucleus to convert it into an oosphere:
the male emits a small number of sperms, long flagellum-like bodies,
each with a nucleus; and these, by their wriggling, detach
themselves from the central core, no longer nucleated. The male
gametogonium with its protruded sperms was termed the "Polymitus
form," and was by some regarded as a degeneration-form, until
MacCallum discovered that a "flagellum" regularly undergoes sexual
fusion with an oosphere in Halteridium, as has since been found in
the other genera. The oosperm (Y) so formed is at first motile
("ookinete"), as it is in Haemosporidae, and passes into the
epithelium of the stomach of the gnat and then through the wall,
acquiring a cyst-wall and finally projecting into the coelom (a-e).
Here it segments into a number of spheres ("zygotomeres" of Ross)
corresponding to the Coccidian spores, but which never acquire a
proper wall (f). These by segmentation produce at their surface an
immense quantity of elongated sporozoites (the "zygotoblasts" or
"blasts" of Ross, Fig. 35, g), these are ultimately freed by the
disappearance of the cyst-wall of the oosperm, pass through the
coelom into the salivary gland (h), and are discharged with its
secretion into the wound that the gnat inflicts in biting. In the blood
the blasts follow the ordinary development of merozoites in the blood
corpuscle, and the patient shows the corresponding signs of fever.
This has been completely proved by rearing the insect from the egg,
feeding it on the blood of a patient in whose blood there were
ascertained to be the germs of a definite species of Haemamoeba,
sending it to England, where it was made to bite Dr. Manson's son,
who had never had fever and whose blood on repeated examination
had proved free from any germs. In the usual time he had a well-
defined attack of the fever corresponding to that germ, and his blood
on examination revealed the Haemamoeba of the proper type. A few
doses of quinine relieved him of the consequences of his mild
martyrdom to science. Experiments of similar character but of less
rigorous nature had been previously made in Italy with analogous
results. Again, it has been shown that by mere precautions against
the bites of Anopheles, and these only, all residents who adopted
them during the malarious season in the most unhealthy districts of
Italy escaped fever during a whole season; while those who did not
adopt the precautions were badly attacked.[113]

Anopheles flourishes in shallow puddles, or small vessels such as

tins, etc., the pools left by dried-up brooks and torrents, as well as
larger masses of stagnant water, canals, and slow-flowing streams.
Sticklebacks and minnows feed freely on the larvae and keep down
the numbers of the species; where the fish are not found, the larvae
may be destroyed by pouring paraffin oil on the surface of the water
and by drainage. A combination of protective measures in Freetown
(Sierra Leone) and other ports on the west coast of Africa, Ismailia,
and elsewhere, has met with remarkable success during the short
time for which it has been tried; and it seems not improbable, that as
the relatively benign intermittent fevers have within the last century
been banished from our own fen and marsh districts, so the Guinea
coast may within the next decade lose its sad title of "The White
Man's Grave."

So closely allied to this group in form, habit, and life-cycle are some
species of the Flagellate genus Trypanosoma, that in their less
active states they have been unhesitatingly placed here (see p. 119).
Schaudinn has seen Trypanosomic characters in the "blasts" of this
group, which apparently is the most primitive of the Sporozoa and a
direct offshoot of the Flagellates.

The Myxosporidiaceae (Fig. 36) are parasitic in various cold-

blooded animals. They are at least binucleate in the youngest free
state, and become large and multinucleate apocytes, which may bud
off outgrowths as well as reproduce by spores. The spores of the
apocyte are not produced by simultaneous breaking up, but by
successive differentiation. A single nucleus aggregates around itself
a limited portion of the cytoplasm, and this again forms a membrane,
becoming an archespore or a "pansporoblast," destined to produce
two spores; within this, nuclear division takes place so as to form
about eight nuclei, two of which are extruded as abortive, and of the
other six, three are used up in the formation of each of the two
spores. Of these three nuclei in each spore, two form nematocysts,
like those of a Coelenterate (p. 246 f.), at the expense of the
surrounding plasm; while the third nucleus divides to form the two
final nuclei of the reproductive body. The whole aggregate of the
reproductive body and the two nematocysts is enveloped in a bivalve
shell. In what we may call germination, the nematocysts eject a
thread that serves for attachment, the valves of the shell open, and
the binucleate mass crawls out and grows afresh. Nosema bombycis
Nägeli (the spore of which has a single nematocyst) is the organism
of the "Pébrine" of the silkworm, which was estimated to have
caused a total loss in France of some £40,000,000 before Pasteur
investigated the malady and prescribed the effectual cure, or rather
precaution against its spread. This consisted in crushing each
mother in water after it had laid its eggs and seeking for pébrine
germs. If the mother proved to be infected, her eggs were destroyed,
as the eggs she had laid were certain to be also tainted. Balbiani
completed the study of the organism from a morphological
standpoint. Some Myxosporidiaceae produce destructive epidemics
in fish.

Fig. 36.—A, Myxidium lieberkühnii, amoeboid phase; B, Myxobolus mülleri,

spore with discharged nematocysts (ntc); C, spores (psorosperms) of a
Myxosporidian. ntc, nematocysts. (From Parker and Haswell.)

The Dolichosporidia or Sarcosporidiaceae are, in the adult state,

elongated sacs, often found in the substance of the voluntary
muscles, and known as "Rainey's" or "Miescher's Tubes"; they are at
first uninucleate, then multinucleate, and then break up successively
into uninucleate cells, the spores, in each of which, by division, are
formed the sickle-shaped zoospores.[114]

CHAPTER V

PROTOZOA (CONTINUED): FLAGELLATA

III. Flagellata.
Protozoa moving (and feeding in holozoic forms) by long flagella:
pseudopodia when developed usually transitory: nucleus single or if multiple
not biform: reproduction occurring in the active state and usually by
longitudinal fission, sometimes alternating with brood-formation in the cyst or
more rarely in the active state: form usually definite: a firm pellicle or distinct
cell-wall often present.

The Flagellates thus defined correspond to Bütschli's group of the

Mastigophora. The lowest and simplest forms, often loosely called
"Monads," are only distinguishable from Sarcodina (especially
Proteomyxa) and Sporozoa by the above characters: their artificial
nature is obvious when we remember that many of the Sarcodina
have a flagellate stage, and that the sperms of bisexual Sporozoa
are flagellate (as are indeed those of all Metazoa except Nematodes
and most Crustacea). Even as thus limited the group is of enormous
extent, and passes into the Chytridieae and Phycomycetes
Zoosporeae on the one hand, and by its holophytic colonial
members into the Algae, on the other.[115]

Classification.
A. Fission usually longitudinal
(transverse only in a cyst), or if
multiple, radial and complete:
pellicle absent, thin, or if armour-
like, with not more than two valves.
I. Food taken in at any part of the
body by pseudopodia 1. PANTOSTOMATA
Multicilia Cienk.; Mastigamoeba F. E. Sch. (Fig. 37, 4).
II. Food taken in at a definite point
or points, or by absorption, or
nutrition holophytic.
1. No reticulate siliceous shell.
Diameter under 500 µ
(1⁄50").
* Contractile vacuole
simple (one or more).
(α) Colourless:
reserves usually
fat: holozoic,
saprophytic or
parasitic 2. Protomastigaceae
(β) Plastids yellow or
brown: reserves
fat or proteid:
nutrition variable:
body naked,
often amoeboid
in active state (C.
nudae), or with a
test, sometimes
containing
calcareous discs
("coccoliths,"
"rhabdoliths") of
peculiar form (C.
loricatae) 3. Chrysomonadaceae
Chromulina Cienk.; Chrysamoeba Klebs;
 Hydrurus Ag. Dinobryon Ehrb. (Fig. 37, 11);
Syncrypta Ehrb. (Fig. 37, 12); Zooxanthella
Brandt; Pontosphaera Lohm.;
Coccolithophora Lohm.; Rhabdosphaera
Haeck.
(γ) Green, (more
rarely yellow or
brown) or
colourless:
reserves starch:
fission
longitudinal 4. Cryptomonadaceae
Cryptomonas Ehrb. (Fig. 37, 9); Paramoeba
Greeff.
(δ) Green (rarely
colourless):
fission multiple,
radial 5. Volvocaceae
** System of contractile
vacuoles complex,
with accessory
formative vacuoles or
reservoir, or both.
(ε) Pellicle delicate or
absent:
pseudopodia
often emitted:
excretory pore
distinct from
flagellar pit:
reserves fat 6. Chloromonadaceae
Chloramoeba Lagerheim; Thaumatomastix,
Lauterborn.
(ζ) Pellicle dense, 7. Euglenaceae
 tough or hard,
often wrinkled or
striate: contractile
vacuole
discharging by
the flagellar pit.
Nutrition variable
Euglena Ehrb.; Astasia Duj. (Fig. 37, 3);
Anisonema Duj.; Eutreptia Perty (Fig. 42, p.
124); Trachelomonas Ehrb. (Fig. 37, 1);
Cryptoglena Ehrb.
2. Skeleton an open network of
hollow siliceous spicules.
Plastids yellow. Diameter
under 500 µ. 8. Silicoflagellata
Dictyocha Ehrb.
3. Diameter over 500 µ. Mouth
opening into a large
reticulate endoplasm:
flagella 1, or 2, very
unequal. 9. Cystoflagellata
Noctiluca Suriray (Fig. 48); Leptodiscus R. Hertw.
B. Fission oblique or transverse: flagella
two, dissimilar, the one coiled round
the base of the other or in a
traverse groove; pellicle often
dense, of numerous armour-like
plates 10. Dinoflagellata
Ceratium Schrank; Gymnodinium Stein; Peridinium Ehrb. (Fig.
46); Pouchetia Schütt; Pyrocystis Murray (Fig. 47); Polykrikos
Bütschli.
The Protomastigaceae and Volvocaceae are so extensive as to
require further subdivision.

Protomastigaceae
I. Oral spots 2. Flagella distant in pairs. Distomatidae
II. Oral spot 1 or 0.
A. Flagellum 1.
(a) No anterior process: often
parasitic Oikomonadidae
Oikomonas K. (Figs. 37, 2, 8); Trypanosoma Gruby
(Fig. 39, a-f); Treponema Vuill. (Fig. 39, g-i).
(b) Anterior process unilateral or
proboscidiform: cell often
thecate Bicoecidae
Bicoeca Clark; Poteriodendron St.
(c) Anterior process a funnel,
surrounding the base of the
flagellum: cells often
thecate.
(i.) Funnel free Craspedomonadidae
Codosiga Clark; Monosiga Cl.; Polyoeca Kent;
Proterospongia Kent; Salpingoeca Cl.
(ii.) Funnel not emerging
from the general
gelatinous investment Phalansteridae
B. Flagella 2, unequal or dissimilar in
function, the one sometimes
short and thick.
(a) Both flagella directed
forwards Monadidae