This page intentionally left blank Antiepileptic Drugs Combination Therapy and Interactions This book reviews the use of antiepileptic drugs focussing on the interactions between these drugs, and between antiepileptics and other drugs. These interactions can be beneficial or can cause harm. The aim of this book is to increase awareness of the possible impact of combination pharmacotherapies. Pharmacokinetic and pharmacodynamic interactions are discussed sup- ported by clinical and experimental data. The book consists of five parts covering the general concepts and advantages of combination therapies, the principles of drug interactions, the mechanisms of interactions, drug interactions in specific populations or in patients with co-mor- bid health conditions, concluding with a look at the future directions for this field of research. The book will be of interest to all who prescribe antiepileptics to epileptic and non-epileptic patients, including epileptologists, neurologists, neuropediatricians, psychiatrists and general practitioners. Antiepileptic Drugs Combination Therapy and Interactions Edited by Jerzy Majkowski The Foundation of Epileptology, Warsaw Blaise F. D. Bourgeois Harvard Medical School, USA Philip N. Patsalos Institute of Neurology, UK and Richard H. Mattson Yale University School of Medicine, USA cambridge university press Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge cb2 2ru,UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521822190 © Cambridge University Press 2005 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2005 isbn-13 978-0-511-12593-5 eBook (NetLibrary) isbn-10 0-511-12593-3 eBook (NetLibrary) isbn-13 978-0-521-82219-0 hardback isbn-10 0-521-82219-x hardback Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Contents List of contributors Page ix Foreword Giuliano Avanzini xiii Foreword Torbjörn Tomson xv Acknowledgements xvii Part I Introduction1 1Combination therapy of diseases: general concepts3 Emma Mason and Philip A. Routledge 2Combination therapy with antiepileptic drugs: potential advantages and problems 16 Richard H. Mattson 3Pharmacogenetic aspects 26 Matthew C. Walker, Michael R. Johnson and Philip N. Patsalos Part II Pharmacokinetic interactions 45 4Pharmacokinetic principles and mechanisms of drug interactions 47 Philip N. Patsalos 5Predictability of metabolic antiepileptic drug interactions 57 Edoardo Spina, Emilio Perucca and Rene Levy 6Influence of food and drugs on the bioavailability of antiepileptic drugs 93 Carlos A. Fontes Ribeiro 7Interactions between antiepileptic drugs 111 Bernhard Rambeck and Theodor W. May 8Interactions between antiepileptic and non-antiepileptic drugs 139 Jerzy Majkowski and Philip N. Patsalos v vi Contents Part III Pharmacodynamic interactions 179 9Pharmacodynamic principles and mechanisms of drug interactions 181 Blaise F. D. Bourgeois 10 Methods for assessing pharmacodynamic interactions 193 Blaise F. D. Bourgeois 11 Experimental studies of pharmacodynamic interactions 208 Stanislaw J. Czuczwar 12 Clinical studies of pharmacodynamic interactions 228 John R. Pollard and Jacqueline French 13 Clinical studies of pharmacodynamic interactions between antiepileptic drugs and other drugs 241 Gaetano Zaccara, Andrea Messori and Massimo Cincotta Part IV Drug interactions in specific patient populations and special conditions 255 14 Antiepileptic drug interactions in children 257 Olivier Dulac, Elizabeth Rey and Catherine Chiron 15 Antiepileptic drug interactions in the elderly 273 Jeannine M. Conway and James C. Cloyd 16 Antiepileptic drug interactions in pregnancy 294 Mark S. Yerby 17 Antiepileptic drug interactions in handicapped and mentally retarded patients 325 Matti Sillanpää 18 Antiepileptic drugs and sex steroids 341 Richard H. Mattson 19 Antiepileptic drug interactions in patients requiring psychiatric drug treatment 350 Michael R. Trimble and Marco Mula 20 Antiepileptic drugs in non-epileptic health conditions: possible interactions 369 Jerzy Majkowski 21 Drug monitoring in combination therapy 392 Walter Fröscher vii Contents 22 Cognitive side-effects due to antiepileptic drug combinations and interactions 403 Albert P. Aldenkamp, Mark de Krom, Irene Kotsopoulos and Jan Vermeulen Part V Conclusions and future perspectives 419 23 Selection of drug combinations in clinical practice: current and future perspectives 421 Jerzy Majkowski 24 Future research: an experimental perspective 441 Rob A. Voskuyl, Daniel M. Jonker and Fernando H. Lopes da Silva 25 Future research: a clinical prospective 458 Carlos A. Fontes Ribeiro Index 475 List of contributors Professor Albert P.Aldencamp Dr Mark de Krom Department of Neurology, University Department of Neurology, University Hospital of Maastricht, PO Box 21, NL 2100 Hospital of Maastricht, PO Box 21, NL 2100 AB, Heeze, The Netherlands AB, Heeze, The Netherlands Professor Blaise F. D. Bourgeois Professor Olivier Dulac Children’s Hospital – HU2, Harvard Medical Hospital Necker-Enfants Malades, 149 Rue School, 300 Longwood Avenue, Boston, de Sevres, Paris 75015, France MA 02115, USA Professor Carlos A. Fontes Ribeiro Department of Pharmacology, Dr Catherine Chiron Faculty of Medicine, 3000 Coimbra, Hospital Necker-Enfants Malades, 149 Rue Portugal de Sevres, Paris 75015, France Professor Jacqueline French Dr Massimo Cincotta Department of Neurology, 3 West Gates, Unit of Neurology, Santa Maria Nuova Hospital of the University of Pennsylvania, Hospital, Florence, Italy 3400 Spruce St, PA 19104, USA Dr James C. Cloyd Professor Walter Fröscher College of Pharmacy, University of Department of Neurology and Epileptology, Minnesota, Room 7101, Weaver Densford Die Weissenau (Department of Psychiatry I), Hall, 308 Harvard St SE, Minneapolis, University of Ulm, D-88214 Ravensburg, MN 55455 0353, USA Germany Dr Michael R. Johnson Dr Jeannine M. Conway Division of Neurosciences and Psychological College of Pharmacy, University of Medicine, Imperial College London, Minnesota, 7-170 WDH, 308 Harvard St SE, Charing Cross Hospital, London, Minneapolis, MN 55455, USA W6 8RP, UK Professor Stanislaw J. Czuczwar Dr Daniel M. Jonker Department of Pathophysiology, Medical Epilepsy Institute of the Netherlands (SEIN), Academy, Jaczewskiego 8, 820-090 Lublin, Achterweg 5, NL 21 03 SW, Poland Heemstede, The Netherlands ix x List of contributors Dr Irene Kotsopoulos Professor Philip N. Patsalos Department of Neurology, University Pharmacology and Therapeutic Unit, Hospital of Maastricht, PO Box 21, Department of Clinical and Experimental NL 2100 AB, Heeze, The Netherlands Epilepsy, Institute of Neurology, Queen Square, London, WC1N 3BG; The National Professor Rene Levy Society for Epilepsy, Chalfont St Peter, UK Department of Pharmaceutics, School of Pharmacy, University of Washington, Professor Emilio Perucca Health Sciences Center H-Wing, Suite 272, Clinical Pharmacology Unit, University of Seattle, WA 98195, USA Pavia, Piazza Botta 10, I 27100 Pavia, Italy Professor Fernando H. Lopes da Silva Dr John R. Pollard Epilepsy Institute of the Netherlands Department of Neurology, 3 West Gates, (SEIN), Achterweg 5, NL 21 03 SW, Hospital of the University of Pennsylvania, Heemstede, The Netherlands 3400 Spruce St, PA 19104, USA Professor Jerzy Majkowski Dr Bernhard Rambeck Diagnostic and Therapeutic Center for Biochemisches Labor der Gesellschaft für Epilepsy, Foundation of Epileptology, ul Epilepsieforschung, Maraweg 13, D-33617 Wiertnicza 122, 02-952 Warsaw, Poland Bielefeld, Germany Dr Emma Mason Dr Elizabeth Rey Department of Pharmacology, Therapeutics Hoˆ pital Saint Vincent de Paul, Paris, France and Toxicology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff, Professor Philip A. Routledge CF14 4XN, UK Department of Pharmacology, Therapeutics and Toxicology, Wales College of Medicine, Professor Richard H. Mattson Cardiff University, Heath Park, Cardiff, Department of Neurology, Yale University CF14 4XN, UK 701 LC1, 33 Cedar Street, New Haven, CT 06510, USA Professor Matti Sillanpää Department of Public Health, 20014 Turku Dr Theodor W. May University, Turku, Finland Biochemisches Labor der Gesellschaft für Epilepsieforchung, Maraweg 13, D-33617 Professor Edoardo Spina Bielefeld, Germany Department of Clinical and Experimental Medicine and Pharmacology, University of Dr Andrea Messori Messina, Policlinico Universitario, Via Unit of Pharmacy, Careggi Hospital, Consolare Valeria, 98125 Messina, Italy Florence, Italy Professor Michael R. Trimble Dr Marco Mula The National Hospital for Neurology and Amadeo Avogadro University, Neurosurgery, Institute of Neurology, C.so Mazzini, 18 28100 Novara, Italy Queen Square, London, WC1N 3BG, UK xi List of contributors Dr Jan Vermeulen Dr Mark S. Yerby Epilepsy centre SEIN, Heemstede, North Pacific Epilepsy Research, 2455 NW The Netherlands Marshall St, Ste 14, Portland, OR 97201, USA Dr Rob A. Voskuyl LACDR, Division of Pharmacology, Dr Gaetano Zaccara Gorlaeus Laboratories,