Valproate
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Valproate (valproic acid, divalproex sodium, sodium valproate)
Depakote, Depakote ER, Depakene, Depacon (IV)
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Summary
Common uses
Generalized epilepsy (absence, tonic-clonic, myoclonic)0, Focal epilepsy0, Bipolar disorder (acute mania, maintenance)0, Migraine prophylaxis0, Status epilepticus (IV)0
Pharmacy
Starting dose
Seizures: 10-15 mg/kg/d divided BID-TID, titrate to therapeutic level (50-100 mcg/mL); bipolar mania: 750 mg/d divided, titrate
Preparations
125, 250, 500 mg delayed-release tablets (Depakote); 250, 500 mg ER tablets (Depakote ER); 125, 250 mg sprinkle capsules; 250 mg/5 mL syrup; 500 mg IV (Depacon)
US FDA Max
60 mg/kg/d (typically up to 3000 mg/d)
Pharmacology
Routes
Oral, IV, rectal (off-label use of injection)
Onset
Anticonvulsant effect within days; mood-stabilizing effect 1-3 weeks
Duration
12 hours (IR); 24 hours (ER)
Half-life
9-16 hours[1]
Bioavailability
~100% (oral); highly (~90%) protein-bound, with non-linear binding above therapeutic levels (free fraction matters clinically in hypoalbuminemia)[1]
Pregnancy
Contraindicated for migraine prophylaxis in pregnancy; high teratogenic risk (neural tube defects, craniofacial anomalies, cardiac defects, cognitive/IQ impairment); avoid in women of childbearing potential without reliable contraception when alternatives exist[1]
Legal status
Purported mechanism
Valproate broadens GABAergic inhibition (raises GABA synthesis, inhibits degradation), blocks voltage-gated sodium channels (slow-inactivated state preference), blocks T-type calcium channels (relevant to absence seizures), and inhibits histone deacetylases (postulated mood-stabilizer mechanism); the multi-mechanism profile underlies the broad-spectrum anticonvulsant activity.0 Hyperammonemic encephalopathy (consider in any unexplained CNS depression), thrombocytopenia, and polycystic ovary syndrome are characteristic chronic-use adverse effects beyond hepatic and pancreatic risks[1].