Clinically significant pharmacokinetic drug interactions between antiepileptic drugs

Pharmacokinetic interactions between antiepileptics represent a major potential complication of epilepsy treatment because drug combinations are common. This review discusses pharmacokinetic drug interactions of clinical significance involving antiepileptics and cytochrome P450 (CYP). Most commonly used antiepileptics are eliminated through hepatic metabolism, catalysed by the enzymes CYP2C9, CYP2C19 and CYP3A4 and uridine diphosphate glucuronosyltransferase (UDGPT). Antiepileptics are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition. Phenytoin, phenobarbiral, primidone and carbamazepine induce CYP and UDPGT enzymes while valproic acid inhibits them. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential and careful dosage adjustments based on serum drug concentration monitoring and clinical observation are the main methods for reducing the risks associated with these interactions.