Litt's drug eruption & reaction manual [25th edition] 9780429020162, 0429020163, 9780429669163, 042966916X, 9780429670657, 0429670656, 9780429672149, 0429672144, 9781351258289, 1351258281

Table of contents :
Content: Introduction. Drug profiles: generic names A-Z. Descriptions of important reactions. Main classes of drugs. Class reactions. Genetics tables. Concordance of synonyms and trade names with generic names.

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25th EDITION

Neil H. Shear

Boca Raton London New York

CRC Press is an imprint of the Taylor & Francis Group, an informa business

CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2019 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-0-367-03065-0 (Paperback) International Standard Book Number-13: 978-0-367-03068-1 (Hardback) This book contains information obtained from authentic and highly regarded sources. While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and do not necessarily reflect the views/opinions of the publishers. The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines. Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently verified. The reader is strongly urged to consult the relevant national drug formulary and the drug companies’ and device or material manufacturers’ printed instructions, and their websites, before administering or utilizing any of the drugs, devices or materials mentioned in this book. This book does not indicate whether a particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole responsibility of the medical professional to make his or her own professional judgements, so as to advise and treat patients appropriately. The authors and publishers have also attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com

CONTENTS Introduction

v

Drug profiles: generic names A–Z

1

Descriptions of important reactions

293

Main classes of drugs

200

Class reactions ACE inhibitors Antiarrhythmics Antibiotics, macrolide Anticonvulsants Antidepressants, tricyclic Antihistamines (H1) Antimalarials Antipsychotics Antiretrovirals Benzodiazepines Beta blockers Biologics Bisphosphonates Calcium channel blockers Cephalosporins Disease-modifying antirheumatic drugs (DMARDS) DPP-4 inhibitors Epidermal growth factor receptor (EGFR) inhibitors Fluoroquinolones Non-steroidal anti-inflammatory drugs (NSAIDS) Proton pump inhibitors (PPI) Statins TNF inhibitors Tyrosine-kinase inhibitors

305 305 307 309 310 313 314 315 317 319 321 322 323 328 329 331 332 337 338 341 343 346 348 349 352

Genetic tables

356

Concordance of synonyms and trade names with generic names

367 iii

Editors’ introductory notes Any drug has the potential to cause an adverse reaction. An adverse drug reaction (ADR) is an unwanted, unpleasant, noxious, or harmful consequence associated with the use of a medication that has been administered in a standard dose by the proper route, for the purpose of prophylaxis, diagnosis, or treatment. Death is the ultimate adverse drug event. ADRs are a major problem in drug therapy. They are the most common of all iatrogenic illnesses that complicate up to 15% of therapeutic drug courses and are a leading cause of morbidity and mortality in healthcare. ADRs should therefore be considered in the differential diagnosis of a wide variety of medical disorders. Many more people – particularly the elderly – are taking more and more prescription and over-the-counter medications. In addition, new drugs are appearing in the medical marketplace on an almost daily basis. It is unsurprising, then, that more and more drug reactions and cutaneous eruptions are emerging. Prevention, diagnosis and treatment of adverse drug events are becoming increasingly complex, and it is to be expected that physicians in all specialties are often perplexed by the nature of ADRs. To this end, I now offer a new and improved edition that has evolved from the treasured Drug Eruption Reference Manual of previous editions. I hope that you will find this new edition informative and valuable. Enjoy! Jerome Z. Litt M..D, Editor emeritus

What is new in 2019? Patients frequently ask about their prescribed drug: "Is it safe?" This text is meant to help all prescribers, dispensers and patients understand what the risk of harm might be; whether it is from a drug reaction or interaction, Litt's D.E.R.M. is the goto information source. How does this information help answer the unanswerable? Simply put, safety is a process, not a question. With the right information at hand a safe environment can thrive; the most up-to-date relevant data help peel away background noise from a seemingly infinite number of sources. This new edition adds additional support to a risk management environment, and we will continue to provide the most up-to-date and relevant information. I look forward to feedback and suggestions. For this edition we are starting to add known genetic risks that are associated with drug reactions and can be screened prior to drug thearpy. This will expand annually as appropriateness of testing becomes part of practice. Litt D.E.R.M. is more than a text. It is part of a community of resources to make prescribing safe and to help optimize therapy. To that end remember that the on-line data is almost double what you see in the text. And it too is kept up-to-date! For me in my practice I am in love with the recently introduced Litt app – an easy portal to the online database, particularly if you are moving between various work spaces. Recently a patient on three critical drugs developed a rash on day 8 of treatment. The Litt app gave me easy access to the likelihood of an exathematous rash for each, and I could provide a clear and thoughtful direction for the immediate future. Finally, I want to note what I call the “Drug Reaction of the Year 2019”! There are indeed new drug reactions, and for me the BIG one is “-gliptin”-induced. When you recognize this and stop the “-gliptins” (dipeptidyl-peptidase 4 inhibitors), in a diabetic patient you will see the reaction clear over the following month. The big “aha” moment for me is when I see a patient with bullous pemphigoid and start to worry about the impact of corticosteroids on their glucose. Even patients who have been on the “-gliptins” for two years will clear. I thank Jerry Litt for this great opportunity and the awesome work of the team at CRC Press to keep on top of all new medications that are making the landscape even more complex. And USE THE APP!! Neil H. Shear, M.D., F.R.C.P.C., F.A.C.P.

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Litt’s Drug Eruption & Reaction Manual – at a glance This 25th edition has been revised and updated throughout to present a quick clinical reference guide to adverse drug reactions (ADRs), side effects, drug interactions and other safety information for prescription and over-the-counter medications. There is also material on reactions caused by classes of drugs, enabling you to see at a glance whether a reaction is common to all the drugs in that particular class, or to a majority of them, or only to a significant few. The aims of this edition remain: 1. To help medical practitioners make informed and safe decisions when diagnosing and prescribing, and also when generally seeking information. 2. To help healthcare professionals remain pharmacovigilant. 3. To provide all physicians, lecturers, educators and pharmacists with an easy-to-use and reliable quick reference tool. The full and comprehensive picture for all drugs – from which our information derives – can be found at our website database (www.drugeruptiondata.com), which is updated continually. (This may now also be accessed via an app.) Space in the manual is, unfortunately, constrained, so full profiles for various generic drugs have been eliminated from this print manual because either they have been withdrawn from the marketplace or they are rarely, if ever, prescribed today; new to this edition are links to their basic profiles in the website database. Important new drugs added to this edition of the manual are noted with an asterisk.

A note on ADRs The incidence and severity of ADRs are influenced by a number of factors: 1. Patient-related factors: • Age – geriatric, pediatric, adolescent . . . older patients are taking more medications—hence more of a possibility of

developing reactions; pediatric patients have more delicate skins; hormonal changes occur in adolescents . . . All these factors play roles in the development of possible adverse reactions. • Gender – male or female – and if the latter, then pregnant/breast-feeding/menopausal . . . • Disease – not only the disease being treated, but also other pre-existing health conditions and comorbid diseases. For

example, atopic patients are at increased risk for serious allergic reactions. Also, there would be an increased risk for hypersensitivity drug reactions if the patient has asthma or lupus erythematosus. • Genetics – a patient could have abnormal drug metabolism by cytochrome P450 due to inheriting abnormal alleles. • Geography – patients living in sunny climes could develop photoxicities from photosensitizing drugs more readily than

those who inhabit cooler, less sunny climates. 2. Drug-related factors: • Type/class of drug – for example, there is a heightened risk of hypersensitivity with the use of beta-blockers (see further the

tables on class reactions). • Duration of therapy – the longer a patient maintains the therapy, the greater the possibility that he/she could develop a

reaction. • Dosage – the greater the dosage, the more likely an adverse side effect. • Bioavailability – the extent to and rate at which the drug enters systemic circulation, thereby accessing the site of action. • Interactions with other drugs – for example, synergistic QT prolongation can occur when two QT prolonging agents, such

as erythromycin + ritonavir, are used together. • Route of administration – intramuscular, intravenous, subcutaneous, and topical administrations are more likely to cause

hypersensitivity reactions; oral medications are less likely to result in drug hypersensitivity. The terms “drug allergy,” “drug hypersensitivity,” and “drug reaction” are often used interchangeably. Drug allergy specifically refers to a reaction mediated by IgE; drug hypersensitivity is an immune-mediated response to a drug agent in a sensitized patient; and drug reactions comprise all adverse events related to drug administration, regardless of etiology.

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Vigilance at point of care: While the possibilities for adverse drug reactions seem endless, we must be on the lookout for any new medication(s) the patient might be taking. A thorough, detailed history of all medications must be made in order to elicit any remote possibility that the drug in question might be the culprit for the side effect. People do not often realize that the common over-thecounter analgesics – aspirin, Tylenol, Advil, Motrin, Naprosyn, and others – are actually medications. Herbals and supplements such as St. John’s wort, ginkgo biloba, and echinacea can be responsible for various hypersensitivity reactions. For example, St. John’s wort, in particular, interacts adversely with SSRIs and tricyclic antidepressants.

Contents of the book, and how to use them 1.

The A–Z The major portion of the manual lists in alphabetical order the 1000 most consulted and most important generic drugs, biologics, and supplements, and the adverse reactions that can arise from their use. An asterisk against the entry title indicates this drug is new to this edition. If you do not find a drug in the main A–Z listing under the name you know it by, you can turn to the concordance of synonyms and trade names to find the generic name it will be listed under. Trade (Brand) name(s) are then listed alphabetically. When there are many trade names, the ten (or so) most commonly recognized ones are listed. Following the trade names is – in parentheses – the latest name of the pharmaceutical company that markets the drug. Many of the names of the companies have changed from earlier editions of this manual because of acquisitions, mergers, and other factors in the pharmaceutical industry. Next appear the Indication(s), the Class in which the drug belongs, and the Half-life of each drug, where known. Drug interactions: many severe, hazardous drug–drug interactions are recorded. Only clinically significant drug interactions that have been reported to trigger potential harm and that could be life threatening have been included here in the profile. These interactions are predictable and well documented in controlled studies; they should be avoided. Pregnancy category: for new drugs approved on or after 30 June 2015 this field gives (where available) a brief summary of the full statement reflecting the risk for pregnant women as given in the prescribing guidelines; health care providers are advised to check the individual label where necessary. An explanation of the categories for older drugs (A, B, C, D and X) can be found on our website www.drugeruptiondata.com. Adverse Drug Reactions: under each drug profile is a list of related ADRs. These adverse events have been classified under the following categories: Skin, Hair, Nails, Mucosal, Cardiovascular, Central Nervous System, Neuromuscular/Skeletal, Gastrointestinal/Hepatic, Respiratory, Endocrine/Metabolic, Genitourinary, Renal, Hematologic, Otic, Ocular, Local, Other. Within each category, the reactions are listed alphabetically. Thus, the order of listing does not reflect severity or frequency in any way. The terminology used to list reaction patterns has been simplified as far as possible by eliminating, for the most part, tags such as “like” (as in “-Psoriasis-like”), “-reactivation,” “-syndrome,” “-dissemination,” “-iform,” etc. The number of reports is given for each reaction in square brackets. The incidence of the most important reactions is given in parentheses where indicated (usually from the full prescribing information for the relevant drug). For example, the profile for Amoxicillin begins: Skin AGEP [28] Anaphylactoid reactions/Anaphylaxis [16] Angioedema (