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Valproic acid poisoning

Matthew D Sztajnkrycer, MD, PhD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


Valproic acid (2-propylpentanoic acid; VPA) is a branched-chain carboxylic acid introduced as an anti-epileptic drug in 1978 in the United States. It is used to treat partial and generalized seizures and acute mania, and as prophylaxis for bipolar disorder and migraine headaches. Although acute VPA intoxication frequently results in mild, self-limited central nervous system depression, serious toxicity and death may occur.

The clinical features and treatment of VPA intoxication are reviewed here. A summary table to facilitate the emergency management of VPA overdose is provided (table 1). The use of VPA as an antiepileptic agent is detailed separately. (See "Overview of the management of epilepsy in adults".)


Although not fully elucidated, the anti-epileptic effects of VPA appear to be mediated by several mechanisms. The pharmacology of VPA is discussed separately. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section on 'Valproate'.)


Valproic acid (VPA) is available in immediate-release and enteric-coated, delayed-release (12 hour) and extended release (24 hour) oral preparations, as well as an intravenous formulation. Delayed and extended release products are typically formulated as divalproex sodium. Therapeutic daily doses range from 500 mg to 2 g in adults or 15 to 60 mg/kg in children [1].

Nonenteric-coated preparations of VPA are rapidly and nearly completely absorbed from the gastrointestinal tract; peak plasma concentrations are observed from one to four hours after ingestion [1]. Peak plasma concentrations occur four to five hours after therapeutic doses of enteric-coated tablets but may be markedly delayed following overdose [1,2]. A multicenter study of VPA ingestions revealed a mean time to peak plasma concentration of 7.4±3.9 hours; 14 percent of patients had peak concentrations delayed greater than 10 hours [3]. In one case report, peak plasma VPA concentrations occurred 17 hours following overdose of divalproex sodium [4].

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Literature review current through: Nov 2017. | This topic last updated: Aug 22, 2016.
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