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Antiepileptic / Mood stabiliser Pregnancy: CONTRAINDICATED in pregnancy unless no alternatives. Major teratogen.

Sodium Valproate

Brand names: Epilim, Episenta, Depakote (valproic acid)

Adult dose

Dose: Loading IV: 40 mg/kg (max 3000 mg) over 5 min; maintenance 500–2500 mg/day
Route: IV or oral
Frequency: IV bolus over 5 min; oral: twice daily (modified-release once daily)
Max: 3000 mg/day
Status epilepticus (second-line): 40 mg/kg IV over 5 minutes. Maintenance: usual 1000–2000 mg/day in 2 divided doses (standard) or once daily (modified-release). Valproate Pregnancy Prevention Programme: women of childbearing potential must use effective contraception — must not be used in pregnancy unless no other alternatives.

Paediatric dose

Dose: 40 mg/kg
Route: IV or oral
Frequency: Status: IV over 5 min; maintenance: twice daily
Max: 60 mg/kg/day (max 2500 mg/day)
Concentration: 100 mg/ml
Status epilepticus: 40 mg/kg IV (max 3000 mg) over 5–10 min. Maintenance (>1 month): 5–7 mg/kg twice daily, increasing to 12.5–15 mg/kg twice daily.

Dose adjustments

Renal

No dose adjustment required; monitor for toxicity.

Hepatic

Contraindicated in hepatic impairment — hepatotoxicity risk.

Paediatric weight-based calculator

Status epilepticus: 40 mg/kg IV (max 3000 mg) over 5–10 min. Maintenance (>1 month): 5–7 mg/kg twice daily, increasing to 12.5–15 mg/kg twice daily.

Clinical pearls

  • MHRA: Valproate must not be used in women of childbearing potential without Pregnancy Prevention Programme
  • Therapeutic range: 50–100 mg/L
  • Carbapenems can halve valproate levels within 24 hours — avoid combination
  • Good broad-spectrum AED for generalised epilepsies, especially absence and myoclonic
  • Annual liver function monitoring recommended

Contraindications

  • Hepatic impairment or liver disease
  • Personal or family history of severe hepatic dysfunction
  • Mitochondrial disorders (Alpers-Huttenlocher syndrome)
  • Porphyria
  • Pregnancy (unless no alternative — Valproate PPP)

Side effects

  • Nausea and vomiting
  • Weight gain
  • Tremor
  • Hair loss (alopecia)
  • Hepatotoxicity (potentially fatal, especially children <2 years)
  • Pancreatitis
  • Polycystic ovary syndrome
  • Teratogenicity (neural tube defects, developmental delay)

Interactions

  • Lamotrigine — valproate doubles lamotrigine levels; dose lamotrigine carefully
  • Carbapenem antibiotics — drastically reduce valproate levels
  • Warfarin — inhibits metabolism, increases INR
  • Phenytoin, carbamazepine — complex mutual interactions

Monitoring

  • Serum valproate levels
  • LFTs (baseline and regular)
  • FBC
  • Pregnancy status (women)

Reference: BNFc; BNF; MHRA Drug Safety Update (valproate); NICE CG137. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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