India · Paediatric mg/kg · Adult · Epilepsy · Bipolar Disorder · Migraine Prophylaxis · Valparin · Encorate · Depakote
🩸 LFTs before starting, at 6 months
🩸 FBC (thrombocytopenia risk)
⚖️ Weight — significant weight gain
🧪 TDM trough level after 3–5 days
🤰 Pregnancy test + PPP for women of CP
⚠️ Stop immediately if acute liver failure signs
| Indication | Starting dose | Maintenance | Max dose | TDM target |
|---|---|---|---|---|
| Childhood epilepsy (any type) | 10–15 mg/kg/day in 2 doses | 20–40 mg/kg/day | 60 mg/kg/day | 50–100 mg/L |
| Adult epilepsy (generalised/focal) | 600 mg/day in 2 doses | 1000–2000 mg/day | 2500 mg/day | 50–100 mg/L |
| IV status epilepticus (adult) | 400–800 mg IV bolus over 15 min | 1–2 mg/kg/hr infusion | 2500 mg/day | 50–100 mg/L |
| Bipolar disorder — acute mania | 750 mg/day in divided doses | 1000–2000 mg/day (target level 50–125 mg/L) | 60 mg/kg/day | 50–125 mg/L |
| Migraine prophylaxis (adults only) | 400 mg/day in 2 doses | 500–1000 mg/day | 1500 mg/day | Not routinely monitored |
Sodium valproate (Valparin, Encorate) is a broad-spectrum anticonvulsant and the most widely used antiepileptic drug in India for generalised epilepsy syndromes — particularly juvenile myoclonic epilepsy (JME), childhood absence epilepsy, and generalised tonic-clonic seizures. Its broad efficacy across multiple seizure types, once-or-twice daily dosing with CR formulations, and relatively low cost make it a first-choice AED in Indian epilepsy practice. However, its teratogenicity profile is among the most serious of any drug in current clinical use, requiring strict prescribing protocols for women of childbearing potential.
Valproate causes major congenital malformations in approximately 10% of pregnancies (neural tube defects, cardiac defects, cleft palate, hypospadias) — a rate 3–5 times higher than other antiepileptics. More significantly, valproate exposure in utero causes neurodevelopmental disorders — autism spectrum disorder, ADHD, and intellectual disability — in up to 30–40% of exposed children. These effects are dose-dependent and occur at all doses, including standard therapeutic doses. The UK MHRA, EMA, FDA, and CDSCO have all issued strong warnings. In India, valproate must not be initiated in any woman of childbearing potential without: specialist neurology/psychiatry review confirming it is the only appropriate option, documentation that effective contraception is in place, annual review, and written patient acknowledgment. If a patient on valproate becomes pregnant, do not abruptly stop — seek urgent specialist neurology review.
Fatal hepatotoxicity is a rare but real risk with valproate, most common in children under 2 years of age and those on polypharmacy. Risk factors: age under 2 years, multiple antiepileptics, metabolic liver disease, mitochondrial disorders (POLG mutations — valproate is contraindicated in POLG-related disease). Baseline LFTs must be checked before starting and at 6 months. Warn parents/patients to stop valproate and seek urgent review if they develop jaundice, abdominal pain, vomiting, or unusual fatigue. Hyperammonaemia (elevated blood ammonia) can occur with valproate even without liver enzyme elevation — check ammonia if encephalopathy develops.