Delayed toxicity following ingestion of enteric-coated divalproex sodium (Epival)

Toxicity occurs rapidly after overdose with regular-release valproic acid, but there is less experience with enteric-coated formulations. We report a case of delayed onset of toxicity and time to peak levels after ingestion of enteric-coated divalproex sodium (Epival). The patient was a 24-year-old female who ingested an unknown amount of Epival together with ibuprofen, dimenhydrinate, and ethanol. Ninety minutes after ingestion, the patient had only mild toxicity, and valproic acid was undetectable in her blood. By 13 h post-ingestion, valproate levels were 7450 micromol/L (1,075 mg/L), and the patient was comatose and required endotracheal intubation and mechanical ventilation. The toxicity and pharmacokinetics of valproic acid are discussed in the context of this case, and management guidelines are proposed.