The Renal Drug Handbook 3rd Edition

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The Renal Drug Handbook 3rd Edition

The Renal Drug Handbook Third Edition The Renal Drug Handbook Third Edition Edited by Caroline Ashley and Aileen Cur

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The Renal Drug Handbook Third Edition

The Renal Drug Handbook Third Edition

Edited by

Caroline Ashley and Aileen Currie UK Renal Pharmacy Group

Foreword by

Dr Aine Burns

Radcliffe Publishing Oxford • New York

Radcliffe Publishing Ltd 18 Marcham Road Abingdon Oxon OX14 1AA United Kingdom www.radcliffe-oxford.com Electronic catalogue and worldwide online ordering facility. © 2009 Caroline Ashley and Aileen Currie First Edition 1999 Second Edition 2004 Caroline Ashley and Aileen Currie have asserted their right under the Copyright, Designs and Patents Act 1998 to be identified as the authors of this work. All rights reserved. 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 permission of the copyright owner. Every effort has been made to ensure the accuracy of these guidelines, and that the best information available has been used. This does not diminish the requirement to exercise clinical judgement, and neither the publishers nor the original authors can accept any responsibility for their use in practice. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library. ISBN-13: 978 184619 298 2

Typeset by Pindar NZ, Auckland, New Zealand Printed and bound by TJI Digital, Padstow, Cornwall, UK

Contents Foreword Preface About the editors List of abbreviations Abacavir Abatacept Abciximab Acamprosate calcium Acarbose Acebutolol Aceclofenac Acenocoumarol (nicoumalone) Acetazolamide Acetylcysteine Aciclovir IV Aciclovir oral Acipimox Acitretin Acrivastine Adefovir dipivoxil Adenosine Adrenaline (epinephrine) Albendazole (unlicensed product) Alemtuzumab (MabCampath) Alendronic acid Alfacalcidol Alfentanil Alimemazine tartrate (trimeprazine) Aliskiren fumarate Allopurinol Almotriptan Alteplase (rt-PA) (recombinant human tissue-type plasminogen activator) Aluminium hydroxide Amantadine hydrochloride Amikacin Amiloride hydrochloride Aminophylline Amiodarone hydrochloride Amisulpride Amitriptyline hydrochloride

xiii xiv xviii xix 1 2 3 4 5 6 7 8 10 11 12 14 15 16 17 18 19 20 21 22 23 24 25 27 28 29 30 31 33 34 35 36 37 39 41 42

Amlodipine Amoxicillin Amphotericin IV – Abelcet (lipid complex) Amphotericin IV – Ambisome (liposomal) Amphotericin IV – Amphocil (complex with sodium cholesteryl sulphate) Amphotericin IV – Fungizone Ampicillin Amprenavir Amsacrine Anagrelide Anastrozole Anidulafungin Apomorphine hydrochloride Aprepitant Argatroban Aripiprazole Arsenic trioxide Artemether with lumefantrine Ascorbic acid Aspirin Atazanavir Atenolol ATG (Rabbit) (Thymoglobuline) Atorvastatin Atovaquone Atracurium besilate Auranofin Azathioprine Azithromycin Aztreonam

44 45 46 47

Baclofen Balsalazide sodium Basiliximab Bemiparin sodium (LMWH) Bendroflumethiazide

79 80 81 82 83

49 50 52 53 55 56 57 58 59 60 61 62 63 64 65 66 67 69 70 72 73 74 75 76 77 78

vi  Contents

Benzatropine mesilate (benztropine) Benzbromarone (unlicensed product) Benzylpenicillin Betahistine dihydrochloride Betamethasone Betaxolol hydrochloride Bevacizumab Bezafibrate Bicalutamide Bisacodyl Bisoprolol fumarate Bivalirudin Bleomycin Bortezomib Bosentan Bromocriptine Budesonide Bumetanide Buprenorphine Bupropion hydrochloride (amfebutamone HCl) Buspirone hydrochloride Busulfan

84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102

Cabergoline Calcitonin (salmon)/salcatonin Calcitriol Calcium acetate Calcium carbonate Calcium gluconate Calcium Resonium Candesartan cilexetil Capecitabine Capreomycin Captopril Carbamazepine Carbimazole Carboplatin Carmustine Carvedilol Caspofungin Cefaclor Cefadroxil Cefalexin Cefixime Cefotaxime Cefpodoxime Cefradine

106 107 108 109 110 111 112 113 114 115 116 117 119 120 121 122 123 124 125 126 127 128 129 130

103 104 105

Ceftazidime 131 Ceftriaxone 132 Cefuroxime (oral) 133 Cefuroxime (parenteral) 134 Celecoxib 135 Celiprolol hydrochloride 137 Cetirizine hydrochloride 138 Cetuximab 139 Chloral hydrate 140 Chlorambucil 141 Chloramphenicol 142 Chlordiazepoxide hydrochloride 143 Chloroquine 144 Chlorphenamine maleate (chlorpheniramine) 145 Chlorpromazine hydrochloride 146 Chlorpropamide 148 Chlortalidone (chlorthalidone) 149 Ciclosporin 150 Cidofovir 152 Cilazapril 153 Cilostazol 154 Cimetidine 155 Cinacalcet 157 Cinnarizine 158 Ciprofibrate 159 Ciprofloxacin 160 Cisplatin 161 Citalopram 163 Cladribine 164 Clarithromycin 165 Clindamycin 167 Clobazam 168 Clofazimine 169 Clomethiazole (chlormethiazole) 170 Clomipramine hydrochloride 171 Clonazepam 173 Clonidine hydrochloride 174 Clopidogrel 175 Clozapine 176 Co-amoxiclav (amoxicillin/clavulanic acid) 178 Co-beneldopa (Madopar) 179 Co-careldopa (Sinemet) 180 Co-codamol (paracetamol and codeine phosphate) 181 Codeine phosphate 182 Co-dydramol (paracetamol and dihydrocodeine) 183

Contents  vii

Colchicine Colestipol hydrochloride Colestyramine (cholestyramine) Colistin Cortisone acetate Co-trimoxazole (trimethoprim + sulfamethoxazole) Cyclizine Cyclopenthiazide Cyclophosphamide Cycloserine Cyproterone acetate Cytarabine Cytomegalovirus (CMV) human immunoglobulin (unlicensed product)

184 185 186 187 189

Dacarbazine Daclizumab Dactinomycin Dalteparin sodium (LMWH) Danaparoid sodium Dapsone Daptomycin Darbepoetin alfa Darifenacin Darunavir Dasatinib Daunorubicin Deferasirox Deferiprone Deflazacort Demeclocycline hydrochloride Desferrioxamine mesilate Desirudin (unlicensed product) Desloratadine Desmopressin (DDAVP) Dexamethasone Dexibuprofen Dexketoprofen Diamorphine hydrochloride Diazepam Diazoxide Diclofenac sodium Didanosine Digitoxin Digoxin Dihydrocodeine tartrate

200 201 202 203 205 207 208 209 210 211 212 213 214 215 216 217 218 220 221 222 223 224 225 226 227 228 229 231 232 233 234

190 192 193 194 195 196 197

199

Diltiazem hydrochloride Dipyridamole Disodium etidronate Disodium pamidronate Disopyramide Disulfiram Dobutamine Docetaxel Dolasetron mesilate Domperidone Donepezil hydrochloride Dopamine hydrochloride Dopexamine hydrochloride Dornase alfa Dosulepin hydrochloride (dothiepin) Doxapram hydrochloride Doxazosin Doxorubicin hydrochloride Doxycycline Drotrecogin alfa Duloxetine

235 236 237 238 239 241 242 243 244 245 246 247 248 249 250 252 253 254 255 256 257

Efalizumab Efavirenz Eletriptan Emtricitabine Enalapril maleate Enfuvirtide Enoxaparin sodium (LMWH) Entecavir Epirubicin hydrochloride Eplerenone Epoetin alfa (Eprex) Epoetin beta (Neorecormon) Epoprostenol (prostacyclin) Eprosartan Eptifibatide Erlotinib Ertapenem Erythromycin Escitalopram Esmolol hydrochloride Esomeprazole Estramustine phosphate Etamsylate Ethambutol hydrochloride Ethosuximide Etodolac

258 259 260 261 262 263 264 266 267 268 270 271 272 273 274 275 276 277 279 280 281 282 283 284 285 286

viii  Contents

Etomidate Etoposide Etoricoxib Everolimus (unlicensed product) Exenatide Ezetimibe

288 289 291 293 294 295

Famciclovir Famotidine Felodipine Fenofibrate Fenoprofen Fentanyl Ferrous gluconate Ferrous sulphate Fexofenadine hydrochloride Filgrastim Finasteride Flecainide acetate Flucloxacillin Fluconazole Flucytosine Fludarabine phosphate Fludrocortisone acetate Flumazenil Fluorouracil Fluoxetine Flupentixol Fluphenazine Flurbiprofen Flutamide Fluvastatin Fluvoxamine maleate Folic acid Folinic acid (calcium folinate) Fondaparinux sodium Formoterol fumarate (eformoterol) Fosamprenavir Foscarnet sodium Fosinopril sodium Fosphenytoin sodium Frovatriptan Fulvestrant Furosemide (frusemide)

296 297 298 299 300 302 303 304 305 306 307 308 310 311 313 314 315 316 317 318 320 321 322 324 325 326 327 328 329 330 331 332 333 334 336 337 338

Gabapentin Galantamine Ganciclovir

340 341 342

Gemcitabine Gemfibrozil Gentamicin Glibenclamide Gliclazide Glimepiride Glipizide Glyceryl trinitrate Granisetron Griseofulvin Guanethidine monosulphate

343 344 345 346 347 348 349 350 351 352 353

Haloperidol Heparin Hydralazine hydrochloride Hydrocortisone acetate Hydrocortisone sodium succinate Hydromorphone hydrochloride Hydroxycarbamide (hydroxyurea) Hydroxychloroquine sulphate Hydroxyzine hydrochloride Hyoscine butylbromide Hyoscine hydrobromide

354 356 357 358 359 360 361 362 363 364 365

Ibandronic acid 366 Ibuprofen 368 Idarubicin hydrochloride 369 Ifosfamide 371 Iloprost 373 Imatinib 374 Imidapril hydrochloride 375 Imipramine hydrochloride 376 Indapamide 378 Indinavir 379 Indometacin 381 Indoramin 383 Inositol nicotinate 384 Insulin – soluble (Actrapid or Humulin S) 385 Interferon alfa-2a (Roferon-A) 386 Interferon alfa-2b 387 Interferon beta 389 Interferon gamma-1b (Immukin) 390 Ipratropium bromide 391 Irbesartan 392 Irinotecan hydrochloride 393 Iron dextran 5% solution 394 Iron sucrose 395 Isoniazid 396

Contents  ix

Isosorbide dinitrate Isosorbide mononitrate Isotretinoin Ispaghula husk Isradipine Itraconazole Ivabradine hydrochloride

397 398 399 400 401 402 404

Ketamine Ketoconazole Ketoprofen Ketorolac trometamol Klean-Prep

405 406 408 410 412

Labetalol hydrochloride Lacidipine Lactulose Lamivudine Lamotrigine Lansoprazole Lanthanum carbonate Leflunomide Lenalidomide Lenograstim Lepirudin Lercanidipine hydrochloride Letrozole Leuprorelin acetate Levamisole (unlicensed product) Levetiracetam Levocetirizine hydrochloride Levofloxacin Levomepromazine (methotrimeprazine) Levothyroxine sodium (thyroxine) Lidocaine hydrochloride Linezolid Liothyronine sodium (tri-iodothyronine) Lisinopril Lithium carbonate Lofepramine Lomustine Loperamide hydrochloride Lopinavir Loratadine Lorazepam Lormetazepam Losartan potassium Lymecycline

413 414 415 416 417 418 419 420 421 422 423 425 426 427 428 429 430 431 432 434 435 436 437 438 439 441 442 443 444 445 446 447 448 449

Mebendazole Medroxyprogesterone acetate Mefenamic acid Mefloquine Meloxicam Melphalan Mepacrine hydrochloride (unlicensed product) Meptazinol Mercaptopurine Meropenem Mesalazine Mesna Metformin hydrochloride Methadone hydrochloride Methenamine hippurate Methotrexate Methyldopa Methylprednisolone Metoclopramide hydrochloride Metolazone Metoprolol tartrate Metronidazole Mexiletine hydrochloride Miconazole Midazolam Midodrine hydrochloride (unlicensed product) Minocycline Minoxidil Mircera Mirtazapine Misoprostol Mitomycin Mitoxantrone Mivacurium Mizolastine Moclobemide Modafinil Moexipril hydrochloride Montelukast Morphine Movicol (active ingredient is the osmotic laxative polyethylene glycol) Moxifloxacin Moxisylyte (thymoxamine) Moxonidine

450 451 453 455 456 458 460 461 462 463 464 465 466 467 468 469 471 472 473 474 475 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495

496 497 498 499

x  Contents

Muromonab-CD3 (OKT3) (unlicensed product) Mycophenolate

500 501

Nabumetone Nadolol Naftidrofuryl oxalate Nalidixic acid Naloxone hydrochloride Naproxen Naratriptan Nateglinide Nebivolol Nefopam hydrochloride Nelfinavir Neomycin sulphate Neostigmine Netilmicin Nevirapine Nicardipine hydrochloride Nicorandil Nicotinic acid Nifedipine Nimodipine Nisoldipine Nitrazepam Nitrofurantoin Nizatidine Noradrenaline acid tartrate (norepinephrine bitartrate) Norfloxacin Normal human immunoglobulin Nortriptyline Nystatin

502 504 505 506 507 508 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527

Octreotide Oestrogen, conjugated (unlicensed product) Ofloxacin Olanzapine Olmesartan medoxomil Olsalazine sodium Omalizumab Omeprazole Ondansetron Orlistat Orphenadrine hydrochloride Oseltamivir

534

528 529 530 532 533

535 536 537 538 539 540 541 542 543 544 545

Oxaliplatin Oxazepam Oxcarbazepine Oxprenolol hydrochloride Oxybutynin hydrochloride Oxycodone hydrochloride Oxytetracycline

546 547 548 549 550 551 552

Paclitaxel Paliperidone Palonosetron Pancreatin Pancuronium bromide Pantoprazole Papaveretum Paracetamol Parecoxib Paricalcitol Paroxetine Pegfilgrastim Peginterferon alfa Pemetrexed Penicillamine Pentamidine isetionate Pentostatin Pentoxifylline (oxpentifylline) Perindopril erbumine Pethidine hydrochloride Phenelzine Phenindione Phenobarbital (phenobarbitone) Phenoxymethylpenicillin (penicillin V) Phentolamine mesilate Phenytoin Phosphate supplements Phytomenadione (vitamin K1) Pimozide Pindolol Pioglitazone Piperazine Piracetam Piroxicam Pivmecillinam hydrochloride Pizotifen Posaconazole Potassium chloride Pramipexole Pravastatin sodium

553 554 555 556 557 558 559 560 561 563 564 565 566 567 568 569 571 572 573 574 575 576 577 579 580 581 583 584 585 586 587 588 589 590 591 592 593 595 596 597

Contents  xi

Praziquantel (unlicensed product) Prazosin Prednisolone Pregabalin Primaquine phosphate Primaxin (imipenem/cilastatin) Primidone Procainamide hydrochloride Procarbazine Prochlorperazine Procyclidine hydrochloride Proguanil hydrochloride Promazine hydrochloride Promethazine hydrochloride Propafenone hydrochloride Propiverine hydrochloride Propofol Propranolol hydrochloride Propylthiouracil Protamine sulphate Pseudoephedrine hydrochloride Pyrazinamide (unlicensed product) Pyridostigmine bromide Pyridoxine hydrochloride Pyrimethamine

598 599 600 601 602 603 604 606 608 609 610 611 612 613 614 615 616 617 619 620 621 622 623 624 625

Quetiapine Quinagolide Quinapril Quinine

626 627 628 629

Rabeprazole sodium Raloxifene hydrochloride Raltitrexed Ramipril Ranitidine Rasagiline Rasburicase Reboxetine Remifentanil Repaglinide Reteplase Ribavirin (tribavirin) Rifabutin Rifampicin Rimonabant Risedronate sodium Risperidone

630 631 632 633 634 635 636 637 638 639 640 641 643 645 647 648 649

Ritonavir Rituximab Rivastigmine Rizatriptan Rocuronium bromide Ropinirole Rosiglitazone Rosuvastatin Rotigotine

650 652 653 654 655 656 657 658 659

Salbutamol Saquinavir Senna Sertindole Sertraline Sevelamer (Renagel®) Sibutramine hydrochloride Sildenafil Simple linctus Simvastatin Sirolimus Sitagliptin Sodium bicarbonate Sodium chloride Sodium clodronate Sodium fusidate Sodium nitroprusside Sodium valproate Sorafenib Sotalol hydrochloride Spironolactone Stavudine Streptokinase Streptomycin (unlicensed product) Strontium ranelate Sucralfate (aluminium sucrose sulphate) Sulfadiazine Sulfasalazine (sulphasalazine) Sulfinpyrazone Sulindac Sulpiride Sumatriptan Suxamethonium chloride Synercid (quinupristin 150 mg/ dalfopristin 350 mg)

660 661 662 663 665 666 667 668 669 670 671 673 674 675 676 677 678 679 680 681 683 684 685 686 688 689 690 691 692 693 694 695 696

Tacrolimus Tadalafil

698 700

697

xii  Contents

Tamoxifen Tamsulosin hydrochloride Tazocin (piperacillin/tazobactam) Teicoplanin Telbivudine Telithromycin Telmisartan Temazepam Temocillin Temozolomide Tenecteplase Tenofovir disoproxil Terazosin Terbinafine Terbutaline sulphate Terlipressin Tetracycline Thalidomide Theophylline Thiotepa Tiagabine Tigecycline Tiludronic acid Timentin (ticarcillin/clavulanic acid) Timolol maleate Tinidazole Tinzaparin sodium (LMWH) Tioguanine Tiotropium Tipranavir Tirofiban Tizanidine Tobramycin Tolbutamide Tolfenamic acid Tolterodine tartrate Topiramate Topotecan Torasemide Toremifene Tramadol hydrochloride Trandolapril Tranexamic acid Trastuzumab Trazodone hydrochloride Treosulfan Triamcinolone

701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 729 730 731 732 733 734 735 736 738 739 740 741 742 743 744 745 746 747 748 749

Triamterene Trifluoperazine Trimethoprim Trimipramine Triptorelin Tropisetron Tryptophan

750 751 752 753 754 755 756

Urokinase Ursodeoxycholic acid

757 758

Valaciclovir Valganciclovir Valproic acid Valsartan Vancomycin Vardenafil Varenicline Vecuronium bromide Venlafaxine Verapamil hydrochloride Vigabatrin Vildagliptin Vinblastine sulphate Vincristine sulphate Vindesine sulphate Vinorelbine Vitamin B and C preparations Voriconazole

759 760 761 762 763 765 766 767 768 769 771 772 773 774 775 776 777 778

Warfarin sodium

780

Xipamide

781

Zafirlukast Zanamivir Ziconotide Zidovudine Zoledronic acid Zolmitriptan Zolpidem tartrate Zonisamide Zopiclone Zotepine Zuclopenthixol Drugs for malaria prophylaxis Vaccines

782 783 784 785 786 787 788 789 790 791 792 793 794

Foreword This third edition of The Renal Drug Handbook is a fantastic publication. Nephrology is a complex speciality and, increasingly, specialist nurses and paramedics are involved in the care of patients. Each of us needs to be wary of prescribing for renal patients and this handbook provides a highly practical, user-friendly method of ensuring that appropriate prescriptions are given to patients, whether they have normal renal function, renal impairment, transplants or are receiving renal replacement therapy. In addition, the authors give very helpful information on pharmacokinetics and common indications for the use of each drug described. This information is not available in any other single textbook. It is an invaluable resource for all healthcare professionals but particularly for those involved in the care of renal patients. A copy of the second edition can be found chained to note trolleys in all of the wards where renal patients are cared for in my hospital. This third edition is even more comprehensive. Aine Burns FRCP Consultant Nephrologist Centre for Nephrology Royal Free Hampstead NHS Trust September 2008

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Preface Welcome to the third edition of The Renal Drug Handbook. The information contained in this book has been compiled from a wide range of sources and from the clinical experience of the editorial board of the UK Renal Pharmacy Group, all of whom are involved in the pharmaceutical care of renally-impaired patients. As such, some of the information contained in the monographs may not be in accordance with the licensed indications or use of the drug. The Handbook aims to: ●●

●●

provide healthcare professionals with a single reference of easily retrievable, practical information relating to drug use, sourced from the practical experience of renal units throughout the UK. By referring to the monographs, the user is guided in how to prescribe, prepare and administer the drug with due regard to potentially serious drug interactions and to any renal replacement therapy the patient may be undergoing provide a practice-based review of drug utilisation in renal units across the UK indicating, where appropriate, any local methods of use, licensed or otherwise.

In recent years, the classification for chronic kidney disease (CKD) has changed, now being described as stages 1–5. Each stage is defined by the patient’s eGFR (or estimated GFR) which is calculated using the MDRD equation (modification of diet in renal disease). One point to note is that the eGFR is normalised to a standard body surface area of 1.73 m2. There is relatively good correlation between the two equations for calculating renal function in patients of average weight, and either could be used for the majority of drugs. However, eGFR should not be used for calculating drug doses in patients at extremes of body weight nor for drugs with a narrow therapeutic window unless it is first corrected to the actual GFR for that patient. Actual GFR can be calculated from the following equation: Actual GFR = (eGFR x BSA/1.73) At extremes of body weight neither the MDRD nor the Cockcroft-Gault equation is particularly accurate. If an accurate GFR is required, e.g. for some chemotherapy, then an isotope GFR determination should be performed. The information on dosage adjustments in renal impairment given in this book is based on Cockcroft-Gault creatinine clearance and not eGFR, since the majority of published information available is based on creatinine clearance. The Handbook is not intended to offer definitive advice or guidance on how drugs should be used in patients with renal impairment, nor is it a comprehensive and complete list of all drugs licensed in the UK.

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Preface  xv

The range of drugs covered will continue to grow with subsequent editions. The Handbook is not a guide to diagnosis nor to a drug’s side-effect profile, except where adverse drug events are more pronounced in the presence of renal impairment. For more in-depth information, users are advised to refer to the Summary of Product Characteristics, the British National Formulary, package inserts or other product data. The use of drugs in patients with impaired renal function can give rise to problems for several reasons: ●●

●●

●● ●● ●● ●●

Altered pharmacokinetics of some drugs, i.e. changes in absorption, tissue distribution, extent of plasma protein binding, metabolism and excretion. In renal impairment these parameters are often variable and interrelated in a complex manner. This may be further complicated if the patient is undergoing renal replacement therapy. For many drugs, some or even all of the altered pharmacokinetic parameters and modified interrelationships are unknown. In such circumstances, the informed professional judgement of clinicians and pharmacists must be used to predict drug disposition. This must be based on knowledge of the drug, its class, chemistry and pharmacokinetics in patients with normal renal function. Sensitivity to some drugs is increased, even if elimination is unimpaired. Many side-effects are particularly poorly tolerated by renally impaired patients. Some drugs are ineffective when renal function is reduced. Renal function generally declines with age, and many elderly patients have a GFR less than 50 mL/min which, because of reduced muscle mass, may not be reflected by an elevated creatinine. Consequently, one can justifiably assume mild renal impairment when prescribing for the elderly.

Many of these problems can be avoided by careful choice and use of drugs. This Handbook seeks to assist healthcare professionals in this process.

Using the monographs ●● ●●

●●

●●

●●

Drug name: The approved (generic) name is usually stated. Clinical use: A brief account of the more common indications in renally impaired patients is given. Where an indication is unlicensed, this is usually stated. Dose in normal renal function: The doses quoted for patients with normal renal function are generally the licensed dosage recommendations stated in the Summary of Product Characteristics for each drug. Where a product is not licensed in the UK, dosage guidelines are provided by the relevant drug company. Pharmacokinetics: Basic pharmacokinetic data such as molecular weight, halflife, percentage protein-binding, volume of distribution and percentage excreted unchanged in the urine are quoted, to assist in predicting drug handling in both renal impairment and renal replacement therapy. ‘–’ denotes ‘not known’ or ‘no data available’. Dose in renal impairment: The level of renal function below which the dose of a drug must be reduced depends largely on the extent of renal metabolism and elimination, and on the drug’s toxicity. Most drugs are relatively well tolerated, have a broad therapeutic index or are metabolised and excreted hepatically, so precise

xvi  Preface

dose modification is unnecessary. In such cases, the user is instructed to ‘dose as in normal renal function’. For renally excreted drugs with a narrow therapeutic index, the total daily maintenance dose may be reduced either by decreasing the dose or by increasing the dosing interval, or sometimes by a combination of both. Dosing guidelines for varying degrees of renal impairment are stated accordingly. ●●

Dose in renal replacement therapy: Details are given for dosing in continuous ambulatory peritoneal dialysis (CAPD), intermittent haemodialysis (HD), haemodiafiltration (HDF), continuous venovenous haemodialysis/haemodiafiltration (CVV HD/HDF), and continuous arteriovenous haemodialysis/haemodiafiltration (CAV HD/HDF), where known. Drugs are categorised into dialysable/not dialysable/ dialysability unknown, to aid the practitioner in making an informed decision for dosing within a particular form of renal replacement therapy. Only a few specific guidelines are given for dosing in continuous arteriovenous/venovenous haemofiltration (CAV/VVH). In general, dosing schedules are the same as those quoted for CAV/VVHD, although it should be borne in mind that CAV/VVH may have a lower drug clearance capacity. Thus the clinician or pharmacist should use informed professional judgement, based on knowledge of the drug and its pharmacokinetics, when deciding whether to further modify dosing regimens.

It should be noted that HDF removes drugs more efficiently than HD, although there is limited information in this area. The Intensive Care Group based at St Thomas’ Hospital, London, has an extensive database on drug removal by haemofiltration and haemodiafiltration, so any extra information can be obtained from them (Tel. 020 7188 7188, pager 1863 or 1830). ●●

●●

●●

Important drug interactions: The interactions listed are those identified by a black spot in Appendix 1 of the British National Formulary. They are defined as those interactions which are potentially serious, and where combined administration of the drugs involved should be avoided, or only undertaken with caution and appropriate monitoring. Users of the monographs are referred to Appendix 1 of the British National Formulary for a more comprehensive list of interactions deemed to be not so clinically significant. Administration : Information is given on reconstitution, route and rate of administration, and other relevant factors. Much of the information relates to local practice, including information on the minimum volume that drugs can be added to. Only the most commonly used and compatible reconstitution and dilution solutions are stated. Other information: Details given here are only relevant to the use of that particular drug in patients with impaired renal function or on renal replacement therapy. For more general information, please refer to the Summary of Product Characteristics for that drug.

Your contribution to future editions is vital. Any ideas, comments, corrections,

Preface  xvii

requests, additions, local practices, etc. on the drugs in the Handbook should be put in writing to the Editors-in-Chief: Caroline Ashley, Pharmacy Department, Royal Free Hospital, Hampstead, London NW3 2QG or Aileen Currie, Pharmacy Department, Crosshouse Hospital, Kilmarnock KA2 0BE. Caroline Ashley Aileen Currie September 2008 The following texts have been used as reference sources for the compilation of the monographs in this book: Electronic Medicines Compendium. British National Formulary No. 55. London: BMJ Publishing Group/RPS Publishing; 2008. Martindale: The Extra Pharmacopoeia. 33rd ed. Pharmaceutical Press; 2002. Bennett WM, et al. Drug Prescribing in Renal Failure: Dosing guidelines for adults. 4th ed. American College of Physicians; 1999. Knoben JE, Anderson PO. Clinical Drug Handbook. 7th ed. Drug Intelligence Publications Inc.; 1993. Schrier RW, Gambertoglio JG. Handbook of Drug Therapy in Liver and Kidney Disease. Little, Brown and Co.; 1991. Dollery C. Therapeutic Drugs. 2nd ed. Churchill Livingstone; 1999. Seyffart G. Drug Dosage in Renal Insufficiency. Kluwer Academic Publishers; 1991. Cyclosporin Interaction File (Novartis Pharmaceuticals UK). Drugdex Database. Micromedex Inc., USA. Drug company information. www.rxlist.com medsafe.govt.nz www.medicinescomplete.com

About the editors Caroline Ashley MSc, BPharm, MRPharmS Lead Pharmacist, Renal Services Royal Free Hospital, London Aileen Currie BSc, MRPharmS Senior Pharmacist, Renal Services Crosshouse Hospital, Kilmarnock

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List of abbreviations ABC ACE ADH AIDS ALG ALT APTT ARF 5-ASA AST ATG AT-II ATN AUC AV BD BP BSA BUN BWt CAPD CAVH CAVHD CIVAS CKD CLCR CLL CMV CNS COX-2 CRF CRIP CSF CSM

advanced breast cancer angiotensin-converting enzyme antidiuretic hormone acquired immunodeficiency syndrome antilymphocyte immunoglobulin alanine transaminase activated partial thromboplastin time acute renal failure 5-aminosalicylic acid aspartate transaminase antithymocyte immunoglobulin angiotensin-II acute tubular necrosis area under the curve atrioventricular twice daily blood pressure British Pharmacopoeia body surface area blood urea nitrogen body-weight continuous ambulatory peritoneal dialysis continuous arteriovenous haemofiltration continuous arteriovenous haemodialysis centralised intravenous additive service chronic kidney disease creatinine clearance chronic lymphocytic leukaemia cytomegalovirus central nervous system cyclo-oxygenase-2 chronic renal failure constant-rate infusion pump cerebrospinal fluid Committee on Safety of Medicines

CVVH

continuous venovenous haemofiltration CVVHD continuous venovenous haemodialysis CVVHDF continuous venovenous haemodiafiltration CyA ciclosporin CYP cytochrome pigment DIC disseminated intravascular coagulation DVT deep-vein thrombosis E/C enteric coated ECG electrocardiogram ECT electroconvulsive therapy ED erectile dysfunction EDTA edetic acid eGFR estimated glomerular filtration rate ERF established renal failure ESRD end-stage renal disease ESRF end-stage renal failure G-6-PD glucose-6-phosphate dehydrogenase GFR glomerular filtration rate GI gastrointestinal GTN glyceryl trinitrate HCL hairy-cell leukaemia HD intermittent haemodialysis HDF intermittent haemodiafiltration HIT heparin-induced thrombocytopenia HMG CoA 3-hydroxy-3-methyl-glutaryl coenzyme A HUS haemolytic uraemic syndrome ICU intensive care unit IM intramuscular INR international normalised ratio IP intraperitoneal IV intravenous LFT liver function test LHRH luteinising hormone-releasing hormone LMWH low molecular weight heparin

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xx  List of abbreviations

LVF MAO MAOI MI MMF MPA M/R mw NNRTI NSAID NSLC NYHA OA OC OD PAH PCA PCP PCR PD PE PO PR PRCA

left ventricular failure monoamine oxidase monoamine oxidase inhibitor myocardial infarction mycophenolate mofetil mycophenolic acid modified release molecular weight non-nucleoside reverse transcriptase inhibitor non-steroidal anti-inflammatory drug non-small-cell lung cancer New York Heart Association osteoarthritis ovarian carcinoma daily primary arterial pulmonary hypertension patient-controlled analgesia Pneumocystis jiroveci pneumonia polymerase chain reaction peritoneal dialysis Parkinson’s disease pulmonary embolism phenytoin equivalent orally rectally pure red cell aplasia

prn PTH PTLD

when required parathyroid hormone post transplant lymphoproliferative disorder PVC polyvinyl chloride RA rheumatoid arthritis RBC red blood cells RhG-CSF recombinant human granulocyte colony-stimulating factor RHuEPO recombinant human erythropoietin SBECD sulphobutylether beta cyclodextrin sodium SC subcutaneous SLE systemic lupus erythematosus SPC Summary of Product Characteristics SR sustained release SSRI selective serotonin reuptake inhibitor SVT symptomatic non-sustained ventricular tachy-arrhythmias elimination half-life T1/2 tri-iodothyronine (liothyronine) T3 thyroxine (levothyroxine) T4 TDM therapeutic-drug monitoring TPN total parenteral nutrition UTI urinary-tract infection WM Waldenström’s macroglobulinaemia

Abacavir  1

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

Abacavir CLINICAL USE

Nucleoside reverse transcriptase inhibitor: ●● Used for HIV infection in combination with other antiretroviral drugs DOSE IN NORMAL RENAL FUNCTION

600 mg daily in 1 or 2 divided doses PHARMACOKINETICS Molecular weight (daltons)

286.3 (670.7 as sulphate)

% Protein binding

49

% Excreted unchanged in urine

2

Volume of distribution 0.8 (L/kg) Half-life – normal/ ESRF (hrs)

1.5/Unchanged

DOSE IN RENAL IMPAIRMENT GFR (mL/min)

20–50 Dose as in normal renal function 10–20 Dose as in normal renal function