Divalproex Sodium

Divalproex sodium (a stable coordination compound of sodium valproate and valproic acid) exerts antiepileptic effects through multiple mechanisms: it blocks voltage-gated sodium channels reducing sustained repetitive firing, enhances GABAergic inhibition by increasing GABA synthesis and inhibiting GABA degradation by GABA transaminase, and inhibits low-threshold T-type calcium channels in thalamic neurons — the principal mechanism underlying its efficacy against absence seizures. This broad mechanistic profile makes it effective across multiple seizure types including focal, generalized, and absence seizures.

Adult

Epilepsy: initially 600 mg daily in 1-2 divided doses, increase by 150-300 mg every 3 days. Maintenance: 1-2 g daily (20-30 mg/kg/day). Max 2.5 g/day. Mania: initially 750 mg daily, usual 1-2 g daily. Migraine prophylaxis: initially 200 mg BD, up to 1.2-1.5 g daily.

Pediatric

1 month-11 years: initially 10-15 mg/kg daily (max 600 mg), maintenance 25-30 mg/kg daily in 2 divided doses. 12-17 years: adult dosing.

Hepatic adjustment

Avoid in severe hepatic impairment; hepatotoxicity risk

Max dose

2.5 g/day (epilepsy); monitor if >45 mg/kg/day

• Acute porphyrias
• Personal/family history of severe hepatic dysfunction
• Known mitochondrial disorders
• Urea cycle disorders
• Active liver disease