Antiepileptic (Valproate)
Pregnancy: Contraindicated — major teratogen (10% structural abnormalities, 30–40% neurodevelopmental disorders). VPPP mandatory.
Sodium Valproate (Paediatric — Epilepsy)
Brand names: Epilim, Epilim Chrono (MR), Episenta (MR)
Adult dose
Dose: Starting: 300 mg BD, increase by 200 mg every 3 days. Target: 1000–2000 mg/day
Route: Oral
Frequency: BD or TDS (standard); OD or BD (MR)
Max: 2500 mg/day
See adult neurology for full dosing and MHRA VPPP warnings
Paediatric dose
Route: Oral or IV
Frequency: BD (standard tablets) or BD–OD (chrono/MR)
Max: 40 mg/kg/day or 2500 mg/day
Concentration: 200 mg/5 mL liquid; 100 mg crushable tablets; Epilim Chrono 200, 300, 500 mg mg/day/ml
BNF for Children: starting 5–10 mg/kg/day BD; increase by 5–10 mg/kg every 3–7 days; target 20–30 mg/kg/day. SE loading: 40 mg/kg IV (max 3000 mg) over 15 min. MHRA VPPP MANDATORY for females ≥13 yrs — must NOT start without compliance confirmed. Annual risk review required ALL patients. Daily dosing — divide by frequency for per-dose amount. Source: BNF for Children 2024; MHRA VPPP 2018; NICE NG217
Dose adjustments
Renal
No dose adjustment required; monitor for hyperammonaemia in renal disease
Hepatic
Contraindicated in hepatic disease — risk of fatal hepatotoxicity (children <3 years highest risk)
Clinical pearls
- MHRA VPPP (Valproate Pregnancy Prevention Programme): mandatory for all female patients — form required annually. Do NOT start without VPPP in place for females ≥13 years.
- Children <3 years: high risk of fatal hepatic failure, especially first 6 months — watch for jaundice, vomiting, drowsiness
- Lamotrigine interaction: if adding lamotrigine to valproate, HALVE the lamotrigine starting dose and titrate more slowly
- Hyperammonaemia: can cause encephalopathy without elevated LFTs — check ammonia if altered consciousness
Contraindications
- Personal or family history of severe hepatic dysfunction
- Hepatic disease
- Porphyria
- Mitochondrial disease (increased hepatotoxicity risk)
- Women of childbearing potential without confirmed VPPP compliance
Side effects
- Tremor
- Weight gain
- Alopecia (reversible)
- GI disturbance
- Hepatotoxicity (especially children <3 years — potentially fatal; highest risk in first 6 months)
- Hyperammonaemia
- Pancreatitis (rare)
- PCOS (long-term)
- Teratogenicity (neural tube defects, autism, developmental delay)
Interactions
- Carbamazepine — valproate increases toxic epoxide of carbamazepine
- Lamotrigine — valproate increases lamotrigine levels (HALVE lamotrigine dose)
- Phenobarbital — valproate increases phenobarbital sedation
- Aspirin — displaces valproate from protein binding (toxicity)
- Mefloquine — reduced valproate levels
Monitoring
- LFTs (first 6 months very closely, then 6-monthly)
- Plasma valproate levels (50–100 mg/L)
- FBC (platelets)
- Ammonia if encephalopathy symptoms
- VPPP compliance annually for females
Reference: BNF for Children; MHRA VPPP 2018; NICE NG217; Epilim SPC. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.
Calculators