Valproate/valproic acid drug interactions

Booth CL, Pollack GM, Brouwer KL. Hepatobiliary disposition of valproic acid and valproate glucuronide use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Hepatology 1996 23(4) 771-780. 

Serious drug interactions are uncommon with valproate. Approximately 25% of valproate metabolism is dependent on CYP isoenzymes. Valproic acid can cause severe liver damage during the first 6 months of treatment. Note interactions with aspirin and the need to monitor plasma free valproate levels. 

Drug Interactions. Enzyme inducers, such as carbamazepine and phenytoin, increase tiagabine clearance and decrease the half-life. Food decreases the rate but not the extent of absorption. Tiagabine is displaced from protein by naproxen, salicylates, and valproate. However, tiagabine does not displace phenytoin, valproic acid, amitrypty-line, tolbutamide, or warfarin. ... 

Drug-drug interactions Lamotrigine Polypharmacy with enzyme inducers is an important susceptibility factor for valproate encephalopathy. Valproic acid-induced hyperammonemic encephalopathy developed exclusively during concomitant treatment with lamotrigine + valproate in a psychiatric setting [174" ]. 

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