Major
Established
Description
The combination of topiramate and valproic acid is associated with hyperammonemia and encephalopathy even without hepatotoxicity, representing a unique metabolic interaction.
Mécanisme
Both drugs inhibit carbonic anhydrase and disrupt the urea cycle; topiramate inhibits carbamoyl phosphate synthetase I, and valproate impairs mitochondrial metabolism, resulting in ammonia accumulation.
Signification clinique
Hyperammonemic encephalopathy can occur without elevated liver enzymes or serum valproate toxicity; the condition is reversible upon drug discontinuation.
Prise en charge
Monitor ammonia levels if altered mental status develops; reduce or discontinue topiramate if hyperammonemia is confirmed.