Pharmacokinetic interactions with anti-epileptic drugs

A large number of interactions with anti-epileptic drugs have been reported, although only a proportion of these are of real and documented clinical significance. A particularly important group of interactions is represented by those resulting in inhibition of anti-epileptic drug metabolism, with the attendant risk of precipitating clinical signs of intoxication. Examples include the inhibition of phenytoin metabolism by sulthiame and isoniazid, the inhibition of carbamazepine metabolism by propoxyphene and the inhibition of phenobarbital metabolism by valproic acid. Plasma protein-binding interactions are unlikely to cause a long-lasting alteration in the response to anticonvulsant drugs, but they are important because they change the relationship between total serum drug levels and pharmacological effect. Phenytoin, phenobarbital, primidone, and carbamazepine are potent inducers of the hepatic drug-metabolizing microsomal enzymes. This may result in an enhanced rate of metabolism and reduced effectiveness of a number of other drugs, including steroid oral contraceptives, oral anticoagulants, quinidine, vitamin D, prednisone, dexamethasone and metyrapone.