Sodium Valproate (Epilim Depakote) 💊
Related Subjects:
|Status Epilepticus (Epilepsy)
|Coma management
|Lorazepam
|Phenytoin
|Levetiracetam
|Epilepsy - General Management
|First Seizure
|Epilepsy in Pregnancy
|Febrile seizures
📖 About
- Check BNF entry here for latest guidance. Avoid in women of childbearing potential
- Broad-spectrum anticonvulsant, also used in migraine prophylaxis and as a mood stabiliser.
- Especially effective in idiopathic generalised epilepsy.
🧬 Mode of Action
- Blocks neuronal sodium (Na+) channels → reduces high-frequency firing.
- Inhibits GABA transaminase → increases GABA levels (inhibitory effect).
- Histone deacetylase inhibitor → possible research/adjunctive uses (e.g. HIV, oncology).
🧾 Indications
- First-choice agent in many seizure types, particularly generalised epilepsies.
- Mania and psychiatric disorders (bipolar disorder).
- Migraine prophylaxis (off-label in some centres).
💊 Dose (Adults)
- Oral therapy: Start 300 mg BD, titrate to 500 mg–1 g BD (max as per BNF, usually up to 2 g/day; occasionally higher in specialist care).
- Status epilepticus (loading): 30 mg/kg IV over 15 minutes (max 3 g). Dilute in 50–100 mL normal saline.
- Status epilepticus (maintenance): 600–1000 mg BD (PO/NG/IV). Switch to enteral as early as possible.
🧪 Monitoring
- Liver function tests (LFTs) for the first 6 months.
- Therapeutic range (trough): 350–700 µmol/L (50–100 mg/L).
- Toxic: >1260 µmol/L (>180 mg/L).
- Check platelets & coagulation if bleeding/bruising suspected.
- Consider haemodialysis in overdose/toxicity.
⛔ Contraindications
- Liver disease or strong family history of liver disease.
- Severe liver failure or mitochondrial disorders.
- Porphyria.
- Teratogenicity: Avoid in women of childbearing potential unless all conditions of the Pregnancy Prevention Programme are fulfilled.
💥 Side Effects
- GI: nausea, vomiting, anorexia, acute pancreatitis.
- Metabolic: increased appetite, weight gain.
- Neuro: tremor, sedation, parkinsonism, cerebellar signs.
- Dermatological: alopecia, DRESS, SJS/TEN.
- Haematological: thrombocytopenia, bone marrow suppression.
- Hyperammonaemia (esp. if mitochondrial disease).
- Teratogenicity: neural tube defects, neurodevelopmental delay.
- False-positive urine dipstick for ketones.
🔄 Interactions
- Isoniazid may ↑ valproate levels.
- Lamotrigine: valproate ↑ lamotrigine levels and rash risk → halve lamotrigine dose if co-prescribed.
- Enzyme inducers (e.g. carbamazepine, phenytoin) may lower valproate levels.
📚 References
