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 o f enteric-coated divalproex sodium (Epival(R)), The patient was a 24-year-o ld female who ingested an unknown amount of Epival(R) together with ibuprof en, dimenhydrinate, and ethanol, Ninety minutes after ingestion, the patien t had only mild toxicity, and valproic acid was undetectable in her blood. By 13 h post-ingestion, valproate levels were 7450 mu mol/L (1,075 mg/L), a nd the patient was comatose and required endotracheal intubation and mechan ical ventilation. The toxicity and pharmacokinetics of valproic acid are di scussed in the context of this case, and management guidelines are proposed , (C) 1999 Elsevier Science Inc.