Drugs During Pregnancy and Lactation Treatment Options and Risk Assessment Third Edition Edited by Christof Schaefer, Paul Peters, and Richard K Miller AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 32 Jamestown Road, London NW1 7BY, UK 225 Wyman Street, Waltham, MA 02451, USA 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA The Boulevard, Langford Lane, Kidlington, Oxford 0X5 1GB, UK Third edition 2015 Copyright © 2015, 2007, 2001 Elsevier B.V All rights reserved 8th edition published in German under the title Arzneimittel in Schwangerschaft & Stillzeit 8th edition 2012 © Elsevier GmbH, Urban & Fischer Verlag, München This 3rd English-language edition of the 8th edition of Arzneimittel in Schwangerschaft & Stillzeit by Christof Schaefer, Horst Spielmann, Klaus Vetter and Corinna Weber-Schöndorfer is published by arrangement with Elsevier GmbH, Urban and Fischer Verlag, Munich The 3rd English-language edition is for the most part an extension and update of this work ISBN 978-0-12-408078-2 (Drugs During Pregnancy and Lactation, 3rd English Edition) ISBN 978-3-437-21203-1 (Arzneimittel in Schwangerschaft & Stillzeit, Auflage 2012) No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0)1865 853333; email: permissions@elsevier.com Alternatively, you can submit your request online by visiting the Elsevier web site at http://elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher 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 Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress For information on all Academic Press publications visit our website at www.store.elsevier.com Typeset by TNQ Books and Journals Printed and bound in Europe 15 16 17 18 10 List of Contributors MARK ANDERSON Great North Children’s Hospital, Newcastle upon Tyne, UK SUSAN M BARLOW Harrington House, Brighton, East Sussex, UK MATITIAHU BERKOVITCH Clinical Pharmacology Unit and Teratogen Information Service, Assaf Harofeh Medical Center, Tel Aviv University, Israel CORNELIA BORISCH Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany CHRISTINA D CHAMBERS Department of Pediatrics, University of California San Diego, La Jolla, CA, USA MAURIZIO CLEMENTI Clinical Genetics Unit, Department of Women’s and Children’s Health, University of Padova, Padova, Italy BENEDIKTE-NOËL CUPPERS Teratology Information Service, Lareb, Den Bosch, The Netherlands MARIA ELLFOLK Teratology Information Service, HUSLAB and Helsinki University Central Hospital, Helsinki, Finland JAN M FRIEDMAN Department of Medical Genetics, University of British Columbia, Vancouver, Canada LEE H GOLDSTEIN Clinical Pharmacology Unit, Haemek Medical Center, Tel Aviv University, Tel Aviv, Israel JULIANE HABERMANN Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany HENRY M HESS Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester NY, USA STEFANIE HULTZSCH Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany ELEANOR HÜTTEL Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany xx List of Contributors ANGELA KAYSER Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany GUDULA KIRTSCHIG Department of Dermatology, VU Medical Centre, Amsterdam, The Netherlands RUTH A LAWRENCE Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA FERNANDA SALES LUIZ VIANNA Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil HELI MALM Teratology Information Service, HUSLAB and Helsinki University Central Hospital, Helsinki, Finland PAUL MERLOB Beilinson Teratology Information Service (BELTIS) Department of Neonatology, Rabin Medical Center, Schneider Children Hospital, Petah Tikva, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel RICHARD K MILLER Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA MARC OPPERMANN Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany ASHER ORNOY Department of Medical Neurobiology, Hebrew University Hadassah Medical School and Israeli Ministry of Health, Jerusalem, Israel STEPHANIE PADBERG Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany MARY PANSE Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany PAUL PETERS Department of Obstetrics, University Medical Center Utrecht, Utrecht, The Netherlands JANINE E POLIFKA Department of Pediatrics, University of Washington, Seattle, WA, USA CHRISTOF SCHAEFER Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany List of Contributors xxi LAVINIA SCHÜLER-FACCINI Teratogen Information Service, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil SALLY STEPHENS UK Teratology Information Service (UKTIS), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK FRANK M SULLIVAN Harrington House, Harrington Road, Brighton, East Sussex, UK GERARD H.A VISSER Department of Obstetrics, University Medical Center, Utrecht, The Netherlands CORINNA WEBER-SCHÖENDORFER Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-University Clinic, Berlin, Germany BERNKE TE WINKEL Teratology Information Service, Lareb, Den Bosch, The Netherlands KATHERINE L WISNER Department of Psychiatry, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA LAURA M YATES UK Teratology Information Service (UKTIS), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK Preface We wish to thank the readership for their suggestions and support of the second English edition We were most appreciative that this textbook was not only available in the German language (eight editions with almost 80,000 copies), but also in Chinese and Russian This third English edition with contributions from the experts in the field continues the tradition of integrating therapies for disease with drug selections during pregnancy and lactation We hope that physicians, health care and cure providers will find that this expanded third English edition enhances their ability to answer the queries frequently asked by concerned women who are planning a pregnancy, are pregnant, or are breastfeeding regarding the risk of medicinal products for themselves, their unborn or breastfed infant We continue to focus the content of this volume for Family Medicine Physicians, Internists, Obstetricians, Pediatricians, Psychiatrists, Medical Geneticists, Dermatologists, Lactation Consultants, Midwives, Nurses, Pharmacists, Psychologists and Toxicologists among all health care providers The third English edition features the most relevant information in regard to acceptable treatment options and allows readers to be confident in their capability to assess the risk of an inadvertent or required treatment/exposure As we have indicated in previous editions, aspects of drug counseling are inadequately supported by various sources of information such as the Physician’s Desk Reference, package leaflets or pharmacotherapy handbooks Formal drug risk classifications or statements such as “contraindicated during pregnancy” may even lead to a simplified perception of risk, e.g., an overestimation of the risk or simple fatalism, and withholding of essential therapy or the prescription of insufficiently studied and potentially risky drugs may result This simplified perception of risk can also lead to unnecessary invasive prenatal diagnostic testing or even to a recommendation to terminate a wanted pregnancy During lactation, misclassification of a drug risk may lead to the advice to stop breastfeeding, even though the drug in question is acceptable or alternatives appropriate for the breastfeeding period are available This book continues to be based on a survey of the literature on drug risks during pregnancy and lactation, as yet unpublished results of recent studies, and current discussions in professional societies dealing with clinical teratology and developmental toxicology Similar to the German edition originally founded by Horst Spielmann, Berlin, this volume reflects accepted “good therapeutic practice” in different clinical settings It is written for clinical decision-makers Arranged according to treatment indications, the third English edition provides an overview of the relevant drugs in the referring medical specialty available today that might be taken by women of reproductive age The volume’s organization facilitates a comparative risk approach, i.e., identifying the drugs of choice for particular diseases or symptoms In addition, recreational drugs, diagnostic procedures (X-ray), vaccinations, poisonings, workplace and environmental contaminants, herbs, supplements and breastfeeding during infectious diseases are discussed in detail The third English edition has been completely revised The content has been adapted for an international readership The contributing authors reflect expertise in a range of clinical specialties, e.g dermatology, obstetrics, pediatrics, internal medicine, psychiatry and many others xxiv Preface Moreover, most authors are active members of the teratology societies including the Organization of Teratogen Information Specialists (OTIS) and the European Network of Teratology Information Services (ENTIS) We are grateful for the outstanding contributions from each of the authors It should be noted that the editors and authors have agreed that the royalties from this volume will be donated to women’s health services in areas of need The royalties from the second English edition helped to support women’s health clinics in Guatemala The Editors and Authors express our appreciation to Kristine Jones, publishing editor, from Elsevier/Academic Press for providing support and advice We thank Shannon Stanton for constant and diligent support during the developmental process and overseeing the transfer of chapters to production and Elizabeth Hormann and Ekkehard Kemmann for translation Finally, the editors wish to express our appreciation to our families for providing us the time and support to complete this edition May the reader use this volume, both in print and electronically, to perform a risk assessment and to examine treatment options for specific diseases in women of reproductive age By providing pre-pregnancy counseling, the editors and authors hope that inappropriate therapeutic, occupational and/or environmental exposures will be minimized Finally, we continue to welcome comments, recommendations and suggestions from our readers using this volume Please share your suggestions with us at the following email address: DrugPregLac@urmc.rochester.edu.* Richard K Miller, Rochester, New York, USA Christof Schaefer, Berlin, Germany Paul Peters, Utrecht, Netherlands * Do not use this email address for patient-related questions because it is not constantly monitored If you have specific patient related questions, please contact the nearest MotherToBaby or ENTIS Teratogen Information Service Thank you Disclaimer Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and interactions It is the r esponsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability 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 General commentary on drug therapy and drug risks in pregnancy Paul Peters, Richard K Miller and Christof Schaefer 1.1 Introduction 1.2 Development and health 1.3 Reproductive stages 1.4 Reproductive and developmental toxicology 1.5 Basic principles of drug-induced reproductive and developmental toxicology 1.6 Effects and manifestations 10 1.7 Pharmacokinetics of drugs in pregnancy 11 1.8 Mechanisms of developmental toxic agents 13 1.9 Causes of developmental disorders 14 1.10 Embryo/fetotoxic risk assessment and plausibility 15 1.11 Classification of drugs used in pregnancy 17 1.12 Paternal use of medicinal products 18 1.13 Communicating the risk of drug use in pregnancy 19 1.14 Risk communication prior to pharmacotherapeutic choice 20 1.15 Risk communication regarding the safety of drugs already used in pregnancy 21 1.16 Teratology information centers 21 1.1 Introduction Most prescribers and users of drugs are familiar with the precautions given concerning drug use during the first trimester of pregnancy These warnings were introduced after the thalidomide disaster in the early 1960s However, limiting the exercise of caution to the first months of pregnancy is both shortsighted and effectively impossible – firstly, because chemicals can affect any stage of pre- or postnatal development; and secondly, because when a woman first learns that she is pregnant, the process of organogenesis has already long since begun (for example, the neural tube has closed) Hence, the unborn could already be inadvertently exposed to maternal drug treatment during the early embryonic period (Figure 1.1) This book is intended for practicing clinicians, who prescribe medicinal products, evaluate environmental or occupational exposures in women who are or may become pregnant Understanding the risks of Drugs During Pregnancy and Lactation http://dx.doi.org/10.1016/B978-0-12-408078-2.00001-9 Copyright © 2015 Elsevier B.V All rights reserved ... Urban and Fischer Verlag, Munich The 3rd English-language edition is for the most part an extension and update of this work ISBN 978-0-12-408078-2 (Drugs During Pregnancy and Lactation, 3rd English... 2 25 Wyman Street, Waltham, MA 02 451 , USA 52 5 B Street, Suite 1800, San Diego, CA 92101-44 95, USA The Boulevard, Langford Lane, Kidlington, Oxford 0X5 1GB, UK Third edition 20 15 Copyright © 20 15, .. .Drugs During Pregnancy and Lactation Treatment Options and Risk Assessment Third Edition Edited by Christof Schaefer, Paul Peters, and Richard K Miller AMSTERDAM