Table Of ContentA REFERENCE GUIDE TO FETAL AND NEONATAL RISK
Drugs in
Pregnancy and
Lactation, Eleventh Edition
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A REFERENCE GUIDE TO FETAL AND NEONATAL RISK
Drugs in Pregnancy and
Lactation, Eleventh Edition
Gerald G. Briggs, BPharm, FCCP
Pharmacist Clinical Specialist (Obstetrics) (Retired)
MemorialCare Center for Women
Miller Children’s Hospital
Long Beach Memorial Medical Center
Long Beach, California
Clinical Professor of Pharmacy
University of California, San Francisco
Adjunct Professor of Pharmacy Practice
University of Southern California, Los Angeles
Adjunct Professor, Department of Pharmacotherapy
Washington State University, Spokane
Roger K. Freeman, MD
MemorialCare Center for Women
Miller Children’s Hospital
Long Beach Memorial Medical Center
Long Beach, California
Director, Mednax Medical Group
Clinical Professor of Obstetrics and Gynecology
University of California, Irvine
Craig V. Towers, MD, FACOG
Professor and Vice Chair
Department of Obstetrics and Gynecology
Division of Maternal-Fetal Medicine
University of Tennessee Medical Center, Knoxville
Alicia B. Forinash, PharmD, FCCP, BCPS, BCACP
Professor of Pharmacy Practice
Saint Louis College of Pharmacy
Clinical Pharmacy Specialist (Obstetrics)
Maternal-Fetal Care Clinic, Saint Mary’s Health Center
Saint Louis, Missouri
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11th edition
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comprehensiveness, or currency of the content of this work.
This work is no substitute for individual patient assessment based upon healthcare professionals’ examination of each patient and consideration
of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to
the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and
not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments.
Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses,
indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should
consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the
manufacturer’s package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify
any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow
therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or
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Foreword
This book is now in its 11th edition and continues to enjoy great success with physicians and other
professionals involved in the care of pregnant and lactating patients. Many of the reviews are exhaustive but
pertinent to the management of pregnant and lactating patients who have already ingested a drug or who are
in need of drug therapy where a cost–benefit analysis may be necessary for appropriate counseling. There are
seldom absolute answers to questions a woman may have when she ingests a drug when pregnant or nursing
because human experience is usually, of necessity, somewhat anecdotal. Even with all the information in this
publication, there are risks that are yet unknown that may apply to a small number of people making the
dictum of not using drugs in pregnancy without good cause still important. The effect of drugs in animals, the
importance of timing and dose, and the effect of environmental factors are all involved in the risks and
benefits of drugs in pregnant and/or lactating women and their fetuses/neonates. These factors are considered
when data are available, but we must admit that in no individual case is the understanding of risks and
benefits absolute.
Because many pregnant and lactating women take substances, both legal and illegal, without the
knowledge of their caregivers, the challenge to understand the risks/benefits of any drug and its interactions
with these substances is daunting. Today, we are just beginning to understand the specific genetic influences
on the action, toxicity, and teratogenicity of drugs in an individual. I expect in the future there will be many
identified genetic factors that will influence therapeutic decisions.
While we will again miss the great contributions of Dr. Sumner Yaffe, the addition of Dr. Craig Towers
and Dr. Alicia Forinash will be very important going forward. It is our hope that the 11th edition will
continue to provide the practitioner appropriate assistance with questions regarding drugs in pregnancy and
lactation.
Roger K. Freeman, MD
University of California, Irvine
I have been using this book since the 1st edition in 1983. As a new coauthor, I now have the opportunity
to participate in its production. This reference book continues to be one of the primary sources for
determining the risks of a particular medication that is or might be used during pregnancy, as well as during
breastfeeding. The 11th edition adds 142 new drugs to the large volume that currently exist, and many of the
drugs in this edition have been updated with new information. In the management and care of a woman who
becomes pregnant while on medications and/or requires drug treatment during pregnancy, the information
supplied in this text provides clinicians with vital data to council their patients. However, a continuing
concern is the absence or very limited human pregnancy data for most of the drugs. Nevertheless, I have no
doubt that this edition will continue to aid practitioners worldwide on this subject.
Craig V. Towers, MD, FACOG
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University of Tennessee Medical Center, Knoxville
In my years as a clinical pharmacist specialist in obstetrics, this book has always been my go to reference.
The summary and in-depth reviews provide valuable information to assist with decisions about medication
safety in pregnancy and lactation. When evaluating drug use during pregnancy, there are several critical things
to consider. Here are two of them. It is important to evaluate both the gestational age and the time when the
various tissues are forming. For example, a drug that increases the risk of oral clefts could be used after the 1st
trimester because the oral tissue would already be formed. It is also important to consider the risks of the
medications and compare these to the embryo–fetal risks of untreated maternal disease. Many maternal
diseases have higher risks for the mother than the embryo–fetal risk from drugs used to treat the disease. I also
want to thank my husband, Brian, and my children, Riley and Cole, for all of their support while I have been
working on this edition.
Alicia B. Forinash, PharmD, FCCP, BCPS, BCACP
Saint Louis, Missouri
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Preface
We are very fortunate to have two respected clinicians join us as coauthors in the preparation of the 11th
edition. Dr. Towers is a maternal–fetal medicine specialist in Tennessee, and Dr. Alicia Forinash is a clinical
pharmacist specialist in obstetrics in St. Louis. Both have published extensively and are knowledgeable in the
effects of drugs on the embryo–fetus and nursing infant.
As with the previous edition, this edition is available in print and online. We have attempted to reduce the
size of the book by removing 33 reviews of drugs that are no longer marketed. If information is needed for
those agents, it can be obtained by referring to the 10th edition.
This edition contains 142 new drug reviews, only two of which have human pregnancy data. None have
reported use during breastfeeding. We also have revised a large number of reviews. Nevertheless, published
human data continue to be very limited for most of the drugs in this book. This places the clinician in a
difficult position. How do they council the patient, who is pregnant or may become pregnant during
treatment, when they are prescribing a medication with no or limited human data and there are no other
drugs with the same mechanism of action that have human pregnancy data? In this situation, the clinician
must decide if treatment of the patient’s condition provides a benefit to her that exceeds the potential risk to
the embryo and/or fetus. The four questions that we ask ourselves when estimating that risk are described
below.
First, is there human pregnancy experience for the drug? In most cases, the answer to this question is no.
Second, is there developmental toxicity in humans with other drugs in the same pharmacologic class? With a
few exceptions (e.g., ACE inhibitors ARII-blockers, β-blockers, nonsteroidal ant-inflammatory drugs), the
answer is not known because many new drugs have highly specific mechanisms and are in a class by
themselves. Third, does the drug cross the placenta? Drugs with molecular weights less than 600 usually cross
easily, but factors such as the elimination half-life, lipid solubility, and plasma protein binding can
significantly modify the amount crossing. However, in the second half of pregnancy, most drugs, even those
with high molecular weight, will cross regardless of these modifying factors. Fourth, does the drug cause
developmental toxicity in animals and can these data be used to estimate human risk? We attempted to answer
this question in a recent article (Briggs GG, et al. Should pregnant women be included in phase IV clinical
drug trials? Am J Obstet Gynecol 2015; 810–5). Animal data for 311 drugs in the 10th edition raised the
possibility of human harm that has been confirmed in 75 drugs (24%). Thus, the animal data do not provide
an adequate assessment, but it can be used in combination with the answers to the other questions and an
assessment of the disease risk to the mother when counseling the patient. This appears to be better than
saying “We just don’t know” when a patient asks if this drug will hurt her developing baby.
As in previous editions, some drug reviews have toll-free telephone numbers for the use of health care
professionals or patients to enroll in observational studies. These studies are an important method for
gathering prospective data on pregnancy exposures for high-risk drugs. In fact, such studies are often the only
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human pregnancy experience available for new drugs and pharmacologic drug classes. The data generated by
these studies and registries can be valuable for the raising of hypotheses of major teratogenicity or providing
some assurance that the agent is not a significant teratogen. Because their importance is so high, health care
professionals and patients are encouraged to call for information about patient enrollment.
Gerald G. Briggs, BPharm, FCCP
Pharmacist Clinical Specialist (Obstetrics) (Retired)
MemorialCare Center for Women
Miller Children’s Hospital
Long Beach Memorial Medical Center
Long Beach, California
Clinical Professor of Pharmacy
University of California, San Francisco
Adjunct Professor of Pharmacy Practice
University of Southern California, Los Angeles
Adjunct Professor, Department of Pharmacotherapy
Washington State University, Spokane
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Contents
Foreword
Preface
Instructions for Use of the Reference Guide
Monographs
Appendix
Index
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