Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs

Lancet Neurol. 2003 Jun;2(6):347-56. doi: 10.1016/s1474-4422(03)00409-5.


There are two types of interactions between drugs, pharmacokinetic and pharmacodynamic. For antiepileptic drugs (AEDs), pharmacokinetic interactions are the most notable type, but pharmacodynamic interactions involving reciprocal potentiation of pharmacological effects at the site of action are also important. By far the most important pharmacokinetic interactions are those involving cytochrome P450 isoenzymes in hepatic metabolism. Among old generation AEDs, carbamazepine, phenytoin, phenobarbital, and primidone induce the activity of several enzymes involved in drug metabolism, leading to decreased plasma concentration and reduced pharmacological effect of drugs, which are substrates of the same enzymes (eg, tiagabine, valproic acid, lamotrigine, and topiramate). In contrast, the new AEDs gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, vigabatrin, and zonisamide do not induce the metabolism of other AEDs. Interactions involving enzyme inhibition include the increase in plasma concentrations of lamotrigine and phenobarbital caused by valproic acid. Among AEDs, the least potential interaction is associated with gabapentin and levetiracetam.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Drug Monitoring
  • Enzyme Induction / drug effects
  • Epilepsy / drug therapy
  • Epilepsy / metabolism*
  • Humans
  • Isoenzymes / metabolism


  • Anticonvulsants
  • Isoenzymes
  • Cytochrome P-450 Enzyme System