Chapter

Drug Interactions

Philip N. Patsalos

in Oxford Textbook of Epilepsy and Epileptic Seizures

Published on behalf of Oxford University Press

Published in print December 2012 | ISBN: 9780199659043
Published online December 2012 | e-ISBN: 9780191751363 | DOI: http://dx.doi.org/10.1093/med/9780199659043.003.0025

Series: Oxford Textbook of

Drug Interactions

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Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment and the treatment goal is seizure freedom. Indeed, monotherapy AEDs can render approximately 65% of newly diagnosed patients seizure-free. However, for the remaining 35% of patients it is common practice to prescribe AEDs in combination so as to achieve optimal seizure control. When AED combinations are used there is an increased risk of pharmacokinetic and/or pharmacodynamic interactions which in turn can result in adverse clinical consequences. For newly licensed AEDs, which can only be prescribed as adjunctive therapy in the first instance, combination therapy is the only option and therefore their propensity to interact is a major consideration. For patients with epilepsy, AEDs are administered for prolonged periods comprising of many years and often for a lifetime and therefore increasing the probability of prescribing polytherapies, particularly for those patients that inevitably develop intercurrent or associated conditions which will require AEDs to be combined with non-AED drugs. Even those patients that respond to monotherapy may similarly experience the consequences of AED interactions as AEDs are added and withdrawn during the optimisation of their monotherapy drug regimen. Furthermore, polytherapy AED regimens are often required to treat patients with multiple seizure types. That AEDs are commonly associated with clinically relevant drug interactions can be attributed to their various characteristics: (a) most AEDs have a narrow therapeutic index so that even small changes in their plasma drug concentration can result in seizure exacerbation or increased adverse effects; (b) the most widely used AEDs (carbamazepine, phenobarbital, phenytoin and valproic acid) have a substantial ability to induce and/or inhibit hepatic metabolism; (c) additionally these AEDs, along with some of the newer AEDs (e.g. eslicarbazepine acetate, felbamate, lamotrigine, oxcarbazepine, retigabine, tiagabine, topiramate, and zonisamide), are susceptible to inhibition and induction of their own metabolism. This chapter will review those interactions that are most frequently encountered clinically and those interactions which because of their magnitude are particularly likely to result in adverse clinical consequences.

Chapter.  6465 words. 

Subjects: Neurology ; Pharmacology

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