Sodium Valproate

• Idiopathic generalised epilepsy refractory to alternatives (women of childbearing age NOT unless PPP conditions met)

Multi-mechanism: ↑ GABA (GAD activation, GABA-T inhibition), Na⁺ channel blockade, T-type Ca²⁺ modulation, HDAC inhibition.

• MCM rate 10%, NDI 30-40%
• MHRA PPP: consent + PPT + effective contraception
• Do NOT initiate in women/girls of childbearing age unless no alternative

Adult

600 mg/day → titrate to 1000–2000 mg/day

IV status

40 mg/kg over 10 min (max 3 g)

• AbsolutePregnancy — unless no alternative (MHRA)
• AbsoluteWomen of childbearing potential without PPP
• AbsoluteMitochondrial disease (POLG), acute porphyria
• AbsoluteLiver disease

• Teratogenicity (NTDs, cardiac, cleft, hypospadias)
• Weight gain
• Tremor, alopecia
• Hepatotoxicity
• Pancreatitis, thrombocytopenia

• • 10% MCM, 30-40% neurodevelopmental impairment (Fetal Valproate Syndrome)
• • IF continued: 5 mg folate/day + vitamin K last month + high-resolution fetal echo/anomaly scan

• Lamotrigine

  Avoid

  Doubles LTG level (halve LTG dose)

• Carbapenems

  Avoid

  Dramatically ↓ valproate — avoid

• Aspirin

  Caution

  Displaces from protein binding → toxicity

• 💡 Annual PPP paperwork mandatory (patient, prescriber, pharmacist)
• 💡 Switch to lamotrigine/levetiracetam preconception whenever feasible