Data for this review were identified by searches of Medline and PubMed with the terms “antiepileptic drug interactions” combined with individual drug names and drug groups; references from relevant articles; and searches of the authors' files. Searches were undertaken between the period Sept 2, 2002 and Feb 11, 2003. Abstracts were included only when a complete published article was not available. Only papers published in English were reviewed. The purpose of the article was not to
ReviewClinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs
Section snippets
Mechanisms of drug interaction
There are two basic types of drug interactions, pharmacokinetic and pharmacodynamic.2, 4 Pharmacokinetic interactions involve a change in the absorption, distribution, or elimination of the affected drug and account for most of the interactions reported to date because they are easily identifiable by a change in drug concentrations in the plasma. Pharmacodynamic interactions, although also important, are less well recognised and are commonly inferred to explain apparently drug-induced changes
Susceptibility to drug interactions
The probability of a drug interaction occurring and the associated clinical consequences are dependent on several factors (panel). Apart from the characteristics of the drugs, patient-related factors have an important role. For example, the effect of a metabolic interaction on a specific CYP isoenzyme can vary among patients in relation to genetic and environmental factors that determine the contribution of that isoenzyme to overall drug elimination. Age is another important source of
Interactions mediated by enzyme induction
Carbamazepine, phenytoin, phenobarbital, and primidone are potent inducers of various CYP isoenzymes (table 1) and they also induce UGT and epoxide hydrolases.2, 25, 38, 62, 63 As a result, these compounds stimulate the metabolism of other AEDs, most notably valproic acid,64, 65 tiagabine,66 ethosuximide,67 lamotrigine,68, 69, 70 topiramate,71 zonisamide,72 oxcarbazepine and its active monohydroxy-metabolite,73 felbamate,74 and many benzodiazepine drugs.75, 76 (table 2). The metabolism of
Prevention and management of adverse AED interactions
AED interactions can have substantial effects on clinical outcome (figure 1), and a therapeutic algorithm for management options in response to such interactions has been proposed (figure 2). A few simple rules can help to limit adverse consequences of AED interactions.2, 139 Multiple drug therapy should be used only when it is clearly indicated. Most patients with epilepsy can be best managed with an individualised dose of a single AED. Most interactions are metabolically based and can be
Search strategy and selection criteria
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