Topiramate-Related Hyperammonemia

Objective: To report a case of hyperammonemia associated with the interaction between topiramate and valproic acid. Case Summary: We present a patient case with topiramate-related hyperammonemia. The patient was on topiramate prior to admission and presented with an elevated ammonia level following 2 doses of valproic acid. The increased dosing frequency of valproic acid further exacerbated the hyperammonemia. On discontinuation of topiramate and the tapering of the dose of valproic acid the patient's ammonia level returned to normal. Discussion: Valproic acid-induced hyperammonemic encephalopathy is well documented and there are several proposed mechanisms. The interaction between valproic acid and topiramate causing drug-induced hyperammonemia encephalopathy is documented in several case reports. The interaction is associated with the addition of topiramate to a patient's medication regimen that previously included valproic acid. Topiramate also has several proposed mechanisms for predisposing patients for hyperammonemia. There are limited data on topiramate monotherapy or long-term use of topiramate use causing hyperammonemia-associated encephalopathy or enhancing hyperammonemia with the addition of valproic acid. Conclusions: This case supports topiramate-related hyperammonemia and the pharmacodynamic interaction with the co-administration of valproic acid.