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The Renal DrugHandbookThe Ultimate Prescribing Guidefor Renal Practitioners5th EditionEdited byCaroline Ashley and Aileen DunleavyUK Renal Pharmacy GroupForeword byProfessor Sir John CunninghamProfessor of NephrologyUniversity College LondonBoca Raton London New YorkCRC Press is an imprint of theTaylor & Francis Group, an informa business

CRC PressTaylor & Francis Group6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742 2019 by Taylor & Francis Group, LLCCRC Press is an imprint of Taylor & Francis Group, an Informa businessNo claim to original U.S. Government worksPrinted on acid-free paperInternational Standard Book Number-13: 978-1-138-62479-5 (Hardback)This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequencesof their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication andapologize 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 byany electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or inany 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-forprofit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopylicense 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 andexplanation without intent to infringe.Visit the Taylor & Francis Web site athttp://www.taylorandfrancis.comand the CRC Press Web site athttp://www.crcpress.com

Foreword to the fifth editionThe Renal Drug Handbook has developed into anessential resource for nephrologists, specialist nursesand pharmacists engaged in the care of these patients.As the field moves forward so also do the therapeuticopportunities, and pitfalls. Fortunately successive editionsof the handbook have kept pace with these advances - thepresent Fifth Edition includes over 900 drug monographs,each containing synoptic but important information for thetarget audience. A particularly strong point to this seriesis that, rather than trying to be clever, the authors havestuck with a simple alphabetical organisation which makesfinding one’s way around extremely easy. Having found thedesired entry, the reader is then confronted with a logical,clear and consistently structured body of information onthe relevant drug, including criteria for use, dosing issues inpatients with normal, reduced and severely reduced renalfunction, drug interactions, metabolism, pharmacokineticsand practicalities of administration. It is this combinationof utility and accessibility that enables the Fifth Editionof The Renal Drug Handbook to set an exceptionally highcrossbar. The book will continue to be available onlineand for this Fifth Edition will be also downloadable tosmartphones. There really is nothing else quite like it.Professor Sir John CunninghamProfessor of Nephrology, University College LondonApril 2018iii

PrefaceWelcome to the fifth edition of The Renal Drug Handbook.The information contained in this book has been compiledfrom a wide range of sources and from the clinical experienceof the editorial board of the UK Renal Pharmacy Group,all of whom are involved in the pharmaceutical care ofrenally-impaired patients. As such, some of the informationcontained in the monographs may not be in accordance withthe licensed indications or use of the drug.The Handbook aims to: provide healthcare professionals with a singlereference of easily retrievable, practical informationrelating to drug use, sourced from the practicalexperience of renal units throughout the UK. Byreferring to the monographs, the user is guidedin how to prescribe, prepare and administer thedrug with due regard to potentially serious druginteractions and to any renal replacement therapy thepatient may be undergoing provide a practice-based review of drug utilisation inrenal units across the UK indicating, where appropriate,any local methods of use, licensed or otherwise.In recent years, the classification for chronic kidneydisease (CKD) has changed, now being described as CKDstages 1–5. Each stage is defined by the patient’s eGFR(or estimated GFR) which is calculated using the MDRD(modification of diet in renal disease) equation. One pointto note is that the eGFR is normalised to a standard bodysurface area of 1.73 m2. There is relatively good correlationbetween the two equations for calculating renal function inpatients of average weight, and either could be used for themajority of drugs. However, eGFR should not be used forcalculating drug doses in patients at extremes of body weightnor for drugs with a narrow therapeutic window unless itis first corrected to the actual GFR for that patient. ActualGFR can be calculated from the following equation:Actual GFR (eGFR BSA/1.73)At extremes of body weight neither the MDRD northe Cockcroft-Gault equation is particularly accurate. If anaccurate GFR is required, e.g. for chemotherapy, then anisotope GFR determination should be performed.The information on dosage adjustments in renalimpairment given in this book is based on Cockcroft-Gaultcreatinine clearance and not eGFR, since the majority ofivpublished information available is based on creatinineclearance.The Handbook is not intended to offer definitive adviceor guidance on how drugs should be used in patients withrenal impairment, nor is it a comprehensive and completelist of all drugs licensed in the UK.The range of drugs covered will continue to grow withsubsequent editions. The Handbook is not a guide todiagnosis nor to a drug’s side-effect profile, except whereadverse drug events are more pronounced in the presenceof renal impairment. For more in-depth information,users are advised to refer to the Summary of ProductCharacteristics, the British National Formulary, packageinserts or other product data.The use of drugs in patients with impaired renalfunction can give rise to problems for several reasons: Altered pharmacokinetics of some drugs, i.e. changesin absorption, tissue distribution, extent of plasmaprotein binding, metabolism and excretion. In renalimpairment these parameters are often variableand interrelated in a complex manner. This may befurther complicated if the patient is undergoing renalreplacement therapy. For many drugs, some or even all, of the alteredpharmacokinetic parameters and modifiedinterrelationships are unknown. In suchcircumstances, the informed professional judgementof clinicians and pharmacists must be used to predictdrug disposition. This must be based on knowledgeof the drug, its class, chemistry and pharmacokineticsin patients with normal renal function. Sensitivity to some drugs is increased, even ifelimination is unimpaired. Many side-effects are particularly poorly tolerated byrenally impaired patients. Some drugs are ineffective when renal function isreduced. Renal function generally declines with age, and manyelderly patients have a GFR less than 50 mL/minwhich, because of reduced muscle mass, may not bereflected by an elevated creatinine. Consequently, onecan justifiably assume mild renal impairment whenprescribing for the elderly.Many of these problems can be avoided by carefulchoice and use of drugs. This Handbook seeks to assisthealthcare professionals in this process.