Drug interactions with valproic acid.

Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants. Since it possesses a wide range of indications, concomitant use with other anticonvulsants, and hence interactions, are not infrequent. Many of these interactions are reciprocal and may have important therapeutic consequences. Valproate acts as a protein binding displacer and/or metabolic inhibitor with respect to a number of other anticonvulsants (phenobarbitone, primidone, phenytoin). Inhibition of metabolism would, in most instances, result in a decrease of the dose requirements of the affected drugs. Valproate is a low clearance drug primarily eliminated by metabolism. Its metabolism is highly inducible by some of the major anticonvulsants (e.g. carbamazepine, phenytoin). Valproate is also highly protein bound in plasma and thus is displaced by salicylates and free fatty acids. However, displacement alone, unlike induced metabolism, should not affect the drug's dose-response relationship.