The Renal Drug Handbook: The Ultimate Prescribing Guide for Renal Practitioners, 5th Edition

1109 Pages·2018·7.25 MB·English

by  Caroline Ashley

The Renal Drug
Handbook
The Ultimate Prescribing Guide
for Renal Practitioners
5th Edition
Edited by
Caroline Ashley and Aileen Dunleavy
UK Renal Pharmacy Group
Foreword by
Professor Sir John Cunningham
Professor of Nephrology
University College London
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
CRC Press
Taylor & Francis Group
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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: 978-1-138-62479-5 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reli-
able data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences
of their use. The authors and publishers have 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 acknowl-
edged 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
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explanation without intent to infringe.
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Foreword to the fifth edition
The Renal Drug Handbook has developed into an clear and consistently structured body of information on
essential resource for nephrologists, specialist nurses the relevant drug, including criteria for use, dosing issues in
and pharmacists engaged in the care of these patients. patients with normal, reduced and severely reduced renal
As the field moves forward so also do the therapeutic function, drug interactions, metabolism, pharmacokinetics
opportunities, and pitfalls. Fortunately successive editions and practicalities of administration. It is this combination
of the handbook have kept pace with these advances - the of utility and accessibility that enables the Fifth Edition
present Fifth Edition includes over 900 drug monographs, of The Renal Drug Handbook to set an exceptionally high
each containing synoptic but important information for the crossbar. The book will continue to be available online
target audience. A particularly strong point to this series and for this Fifth Edition will be also downloadable to
is that, rather than trying to be clever, the authors have smartphones. There really is nothing else quite like it.
stuck with a simple alphabetical organisation which makes
finding one’s way around extremely easy. Having found the Professor Sir John Cunningham
Professor of Nephrology, University College London
desired entry, the reader is then confronted with a logical,
April 2018
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: 978-1-138-62479-5 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reli-
able data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences
of their use. The authors and publishers have 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 acknowl-
edged 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
iii
Preface
Welcome to the fifth edition of The Renal Drug Handbook. published information available is based on creatinine
The information contained in this book has been compiled clearance.
from a wide range of sources and from the clinical experience The Handbook is not intended to offer definitive advice
of the editorial board of the UK Renal Pharmacy Group, or guidance on how drugs should be used in patients with
all of whom are involved in the pharmaceutical care of renal impairment, nor is it a comprehensive and complete
renally-impaired patients. As such, some of the information list of all drugs licensed in the UK.
contained in the monographs may not be in accordance with The range of drugs covered will continue to grow with
the licensed indications or use of the drug. subsequent editions. The Handbook is not a guide to
The Handbook aims to: diagnosis nor to a drug’s side-effect profile, except where
adverse drug events are more pronounced in the presence
• provide healthcare professionals with a single
of renal impairment. For more in-depth information,
reference of easily retrievable, practical information
users are advised to refer to the Summary of Product
relating to drug use, sourced from the practical
experience of renal units throughout the UK. By Characteristics, the British National Formulary, package
referring to the monographs, the user is guided inserts or other product data.
in how to prescribe, prepare and administer the The use of drugs in patients with impaired renal
drug with due regard to potentially serious drug
function can give rise to problems for several reasons:
interactions and to any renal replacement therapy the
patient may be undergoing • Altered pharmacokinetics of some drugs, i.e. changes
• provide a practice-based review of drug utilisation in in absorption, tissue distribution, extent of plasma
renal units across the UK indicating, where appropriate, protein binding, metabolism and excretion. In renal
any local methods of use, licensed or otherwise. impairment these parameters are often variable
and interrelated in a complex manner. This may be
In recent years, the classification for chronic kidney further complicated if the patient is undergoing renal
disease (CKD) has changed, now being described as CKD replacement therapy.
stages 1–5. Each stage is defined by the patient’s eGFR • For many drugs, some or even all, of the altered
pharmacokinetic parameters and modified
(or estimated GFR) which is calculated using the MDRD
interrelationships are unknown. In such
(modification of diet in renal disease) equation. One point
circumstances, the informed professional judgement
to note is that the eGFR is normalised to a standard body
of clinicians and pharmacists must be used to predict
surface area of 1.73 m2. There is relatively good correlation drug disposition. This must be based on knowledge
between the two equations for calculating renal function in of the drug, its class, chemistry and pharmacokinetics
patients of average weight, and either could be used for the in patients with normal renal function.
majority of drugs. However, eGFR should not be used for • Sensitivity to some drugs is increased, even if
calculating drug doses in patients at extremes of body weight elimination is unimpaired.
nor for drugs with a narrow therapeutic window unless it • Many side-effects are particularly poorly tolerated by
renally impaired patients.
is first corrected to the actual GFR for that patient. Actual
• Some drugs are ineffective when renal function is
GFR can be calculated from the following equation:
reduced.
Actual GFR = (eGFR × BSA/1.73) • Renal function generally declines with age, and many
elderly patients have a GFR less than 50 mL/min
At extremes of body weight neither the MDRD nor which, because of reduced muscle mass, may not be
the Cockcroft-Gault equation is particularly accurate. If an reflected by an elevated creatinine. Consequently, one
can justifiably assume mild renal impairment when
accurate GFR is required, e.g. for chemotherapy, then an
prescribing for the elderly.
isotope GFR determination should be performed.
The information on dosage adjustments in renal Many of these problems can be avoided by careful
impairment given in this book is based on Cockcroft-Gault choice and use of drugs. This Handbook seeks to assist
creatinine clearance and not eGFR, since the majority of healthcare professionals in this process.
iv
Preface v
Using the monographs decision for dosing within a particular form of renal
replacement therapy. Only a few specific guidelines
• Drug name: The approved (generic) name is usually
are given for dosing in continuous arteriovenous/
stated.
venovenous haemofiltration (CAV/VVH). In
• Clinical use: A brief account of the more common
general, dosing schedules are the same as those
indications in renally impaired patients is given.
quoted for CAV/VVHD, although it should
Where an indication or route is unlicensed, this is
be borne in mind that CAV/VVH may have a
usually stated.
lower drug clearance capacity. Thus the clinician
• Dose in normal renal function: The doses quoted
or pharmacist should use informed professional
for patients with normal renal function are generally
judgement, based on knowledge of the drug and its
the licensed dosage recommendations stated in the
pharmacokinetics, when deciding whether to further
Summary of Product Characteristics for each drug.
modify dosing regimens.
Where a product is not licensed in the UK, dosage
guidelines are provided by the relevant drug company. It should be noted that HDF removes drugs more
• Pharmacokinetics: Basic pharmacokinetic data such
efficiently than HD, although there is limited information
as molecular weight, half-life, percentage protein-
in this area.
binding, volume of distribution and percentage
excreted unchanged in the urine are quoted, to assist • Important drug interactions: The interactions listed
in predicting drug handling in both renal impairment are those identified by a black spot in Appendix 1
and renal replacement therapy. of the British National Formulary. They are defined
• Metabolism: Very few drugs are 100% excreted via as those interactions which are potentially serious,
either the liver or the kidneys. Many are metabolised and where combined administration of the drugs
by the liver to either active or inactive metabolites, involved should be avoided, or only undertaken with
and some of these may be excreted via the kidneys. caution and appropriate monitoring. Users of the
Pharmacologically active metabolites that undergo monographs are referred to Appendix 1 of the British
renal excretion must be considered when prescribing National Formulary for a more comprehensive list of
the parent drug in patients with renal impairment. interactions deemed to be not so clinically significant.
• Dose in renal impairment: The level of renal • Administration: Information is given on
function below which the dose of a drug must be reconstitution, route and rate of administration,
reduced depends largely on the extent of renal and other relevant factors. Much of the information
metabolism and elimination, and on the drug’s relates to local practice, including information on
toxicity. Most drugs are relatively well tolerated, have the minimum volume that drugs can be added to.
a broad therapeutic index or are metabolised and Only the most commonly used and compatible
excreted hepatically, so precise dose modification is reconstitution and dilution solutions are stated. The
unnecessary. In such cases, the user is instructed to product literature should always be consulted for the
‘dose as in normal renal function’. most up to date information.
• Other information: Details given here are only
For renally excreted drugs with a narrow therapeutic
relevant to the use of that particular drug in patients
index, the total daily maintenance dose may be reduced either with impaired renal function or on renal replacement
by decreasing the dose or by increasing the dosing interval, or therapy. For more general information, please refer to
sometimes by a combination of both. Dosing guidelines for the Summary of Product Characteristics for that drug.
varying degrees of renal impairment are stated accordingly.
Your contribution to future editions is vital. Any ideas,
• Dose in renal replacement therapy: Details are comments, corrections, requests, additions, local practices,
given for dosing in automated peritoneal dialysis/ etc. on the drugs in the Handbook should be put in writing
continuous ambulatory peritoneal dialysis (APD/
to the Editors-in-Chief: Caroline Ashley, Pharmacy
CAPD), intermittent haemodialysis (HD),
Department, Royal Free Hospital, Hampstead, London
intermittent haemodiafiltration (HDF), continuous
NW3 2QG or Aileen Dunleavy, Pharmacy Department,
venovenous haemodialysis/haemodiafiltration
(CVV HD/HDF), and continuous arteriovenous Crosshouse Hospital, Kilmarnock KA2 0BE.
haemodialysis/haemodiafiltration (CAV HD/
HDF), where known. Drugs are categorised into Caroline Ashley
dialysable/not dialysable/dialysability unknown, Aileen Dunleavy
to aid the practitioner in making an informed March 2018
The following texts have been used as reference sources for Schrier RW, Gambertoglio JG. Handbook of Drug
the compilation of the monographs in this book: Therapy in Liver and Kidney Disease. Little,
Brown and Co.; 1991.
electronic Medicines Compendium www.medicines.
Dollery C. Therapeutic Drugs. 2nd ed. Churchill
org.uk/emc
Livingstone; 1999.
British National Formulary 73rd ed. Pharmaceutical
Seyffart G. Drug Dosage in Renal Insufficiency.
Press; 2017.
Kluwer Academic Publishers; 1991.
Sweetman SC. Martindale: The Complete Drug
Cyclosporin Interaction File (Novartis
Reference. 39th ed. Pharmaceutical Press; 2017.
Pharmaceuticals UK).
Accessed via http://www.knowledge.scot.nhs.uk
Drugdex Database. Micromedex 2.0 Inc., USA.
Bennett WM, et al. Drug Prescribing in Renal Failure:
Drug company information.
Dosing guidelines for adults. 5th ed. American
www.rxlist.com
College of Physicians; 2007.
medsafe.govt.nz
Drug Information Handbook. 22nd ed. Lexicomp;
www.medicinescomplete.com
American Pharmacists Association; 2013
http://www.drugbank.ca/drugs
Knoben JE, Anderson PO. Clinical Drug Handbook.
7th ed. Drug Intelligence Publications Inc.; 1993.
vi
About the editors vii
About the editors
Caroline Ashley is the Lead Specialist Pharmacist for School of Pharmacy in 2011. She was 2017 recipient of
Renal Services at the University College London Centre for the BRS Mallick Lecture Award for lifetime services to the
Nephrology and Transplantation, Royal Free Hospital. She renal community.
has over 25 years’ renal experience, and her major areas of Aileen Dunleavy is the Senior Specialist Pharmacist
interest are transplantation and auto-immune renal disease. for Renal Services at the University Hospital Crosshouse,
Caroline was involved in the development of the Renal NHS Ayrshire and Arran, with over 20 years’ renal
National Service Framework, and the NICE guidelines experience. Her major areas of interest are dialysis, anaemia
on Immunosuppression in Renal Transplantation, Renal and CKD. She became an independent prescriber in 2008.
Anaemia, and Acute Kidney Injury. She is the co-editor of She is the co-editor of The Renal Drug Handbook and has
both The Renal Drug Handbook and the Introduction to contributed to the Introduction to Renal Therapeutics,
Renal Therapeutics, and sits on the editorial board of the Drugs in Use and Adverse Drug Reactions. She has been a
British Journal of Renal Medicine. She was the Chair of committee member of the UK Renal Pharmacy Group for
the UK Renal Pharmacy Group from 1996 to 2017, and more than 15 years.
was made Associate Professor of Pharmacy Practice, UCL
List of abbreviations
5-ASA 5-aminosalicylic acid ED erectile dysfunction
ABC advanced breast cancer EDTA edetic acid
ACE angiotensin-converting enzyme eGFR estimated glomerular filtration rate
ACS acute coronary syndrome ERF established renal failure
ADH antidiuretic hormone ESAs erythropoiesis-stimulating agents
AIDS acquired immunodeficiency syndrome ESRD end-stage renal disease
ALG antilymphocyte immunoglobulin ESRF end-stage renal failure
ALT alanine transaminase FSGS focal segmental glomerulosclerosis
APD automated peritoneal dialysis G-6-PD glucose-6-phosphate dehydrogenase
APTT activated partial thromboplastin time GFR glomerular filtration rate
ARBs angiotensin receptor blockers GI gastrointestinal
ARF acute renal failure GTN glyceryl trinitrate
AST aspartate transaminase HCL hairy cell leukaemia / hydrochloride
ATG antithymocyte immunoglobulin HD intermittent haemodialysis
AT-II angiotensin- II HDF intermittent haemodiafi ltration
ATN acute tubular necrosis HIT heparin-induced thrombocytopenia
AUC area under the curve HMG CoA 3-hydroxy-3-methyl-glutaryl coenzyme A
AV atrioventricular HUS haemolytic uraemic syndrome
bd twice daily ICU intensive care unit
BP blood pressure IM intramuscular
BUN blood urea nitrogen INR international normalised ratio
CAPD continuous ambulatory peritoneal dialysis IP intraperitoneal
CAVH continuous arteriovenous haemofiltration IV intravenous
CAVHD continuous arteriovenous haemodialysis LFT liver function test
CKD chronic kidney disease LHRH luteinising hormone-releasing hormone
CLL chronic lymphocytic leukaemia LMWH low molecular weight heparin
CMV cytomegalovirus LVF left ventricular failure
CNS central nervous system M/R modified release
COX-2 cyclo-oxygenase-2 MAO monoamine oxidase
CRCL creatinine clearance MAOI monoamine oxidase inhibitor
CRF chronic renal failure MI myocardial infarction
CRIP constant-rate infusion pump MMF mycophenolate mofetil
CSF cerebrospinal fluid MPA mycophenolic acid
CSM Committee on Safety of Medicines NHL non-Hodgkin’s lymphoma
CVVH continuous venovenous haemofiltration NSAID non-steroidal anti-inflammatory drug
CVVHD continuous venovenous haemodialysis NSLC non-small cell lung cancer
CVVHDF continuous venovenous haemodiafiltration NYHA New York Heart Association
CyA ciclosporin OD daily
CYP cytochrome pigment PAH primary arterial pulmonary hypertension
DIC disseminated intravascular coagulation PCA patient-controlled analgesia
DVT deep-vein thrombosis PCI percutaneous coronary intervention
E/C enteric coated PCP Pneumocystis jiroveci pneumonia
ECG electrocardiogram PCR polymerase chain reaction
ECT electroconvulsive therapy PD Parkinson’s disease / peritoneal dialysis
viii
List of abbreviations ix
PE phenytoin equivalent / pulmonary SIADH syndrome of antidiuretic hormone
embolism secretion
PO orally SLE systemic lupus erythematosus
PR rectally SPC Summary of Product Characteristics
PRCA pure red cell aplasia SR sustained release
prn when required SSRI selective serotonin reuptake inhibitor
PTH parathyroid hormone SVT symptomatic non-sustained ventricular
PTLD post transplant lymphoproliferative tachy-arrhythmias
disorder T½ elimination half-life
PVC polyvinyl chloride T3 tri-iodothyronine (liothyronine)
RA rheumatoid arthritis T4 thyroxine (levothyroxine)
RBC red blood cells TADs tricyclic antidepressants
RhG-CSF recombinant human granulocyte colony- TDM therapeutic- drug monitoring
stimulating factor TPN total parenteral nutrition
RHuEPO recombinant human erythropoietin UTI urinary-tract infection
SBECD sulphobutylether-beta-cyclodextrin sodium WM Waldenström’s macroglobulinaemia
SC subcutaneous