An antiepileptic capsule for absence seizures and complex partial seizures, alone or with other seizure drugs. Its boxed warning covers fatal liver failure, pancreatitis, and serious harm to an unborn baby, so liver tests are checked and it is avoided in pregnancy unless nothing else works.
Narrow therapeutic index. The label directs checking plasma levels against the accepted target range of 50 to 100 mcg/mL when response is unsatisfactory, and thrombocytopenia rises at higher levels.
Life-threatening adverse reactions. Hepatotoxicity, including fatal liver failure, usually in the first 6 months; children under 2 and patients with mitochondrial disorders are at higher risk, so check liver tests before and frequently during therapy. Fetal risk: neural tube defects, other major malformations, and decreased IQ. Pancreatitis, including fatal hemorrhagic cases.
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No specific antidote. Give supportive care and maintain urine output; hemodialysis, or hemodialysis with hemoperfusion, can remove significant drug in overdose. Naloxone has reversed CNS depression but may also reverse its antiseizure effect, so use it cautiously in epilepsy.
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Doses come from the FDA label. Study tool, not for clinical decisions.
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No labeled dose change. Protein binding falls in renal failure, so total levels can mislead.
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Contraindicated in hepatic disease or significant hepatic dysfunction.
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Valproic acid dissociates to the valproate ion in the gut. Its mechanism is not established; antiseizure activity may relate to higher brain GABA concentrations. It is cleared mainly by hepatic glucuronidation and beta-oxidation, with CYP oxidation a minor path, so enzyme inducers such as phenytoin, carbamazepine, and phenobarbital can double its clearance. It is a weak inhibitor of some CYP isozymes, epoxide hydrase, and glucuronosyltransferases.