Valproate / Valproic Acid (Sodium Valproate / Valproic Acid / Divalproex Sodium)
Also sold as: Valparin, Encorate, Depakote, Valance
Pregnancy
Cat D
Lactation
Caution
Schedule
H
Forms
Tablet 200mg (sodium valproate) +7
Indications
- Epilepsy — focal and generalized seizures (broad spectrum)
- Juvenile myoclonic epilepsy (JME)
- Absence seizures
- Bipolar disorder — mania and maintenance
- Migraine prophylaxis
- Status epilepticus (IV)
Adult Dosing
Epilepsy
10–15 mg/kg/day in 2–3 divided doses
Start 200–400mg BD; increase by 200mg every 3–5 days; usual maintenance 1000–2000mg/day
Therapeutic serum level: 50–100 mcg/mL. Max 60mg/kg/day.
Bipolar mania (acute)
750–2500 mg/day in divided doses
Loading dose 20–30mg/kg/day possible in acute mania; titrate to serum level 50–125 mcg/mL
Extended-release (Chrono) formulation preferred for better tolerability
Migraine prophylaxis
500–1000 mg/day
Start 250mg BD; titrate over 4 weeks; max 1000mg/day
Avoid in women of childbearing potential due to teratogenic risk
Pediatric Dosing
AVOID in children <2 years — highest risk of fatal hepatotoxicity. Use oral solution for accurate pediatric dosing. Monitor ammonia and LFTs closely in young children.
Renal Dose Adjustment
| CrCl / eGFR | Dose Adjustment |
|---|---|
| Renal impairment (any degree) | Protein binding reduced — free fraction increased; monitor free valproate levels; dose reduction may be required |
Hepatic Adjustment
CONTRAINDICATED in significant hepatic disease. Hepatotoxicity is most serious adverse effect — fatal in young children <2 years. Monitor LFTs before initiation and frequently in first 6 months.
Pregnancy & Lactation
Pregnancy: Category D
MAJOR TERATOGEN — highest teratogenic risk among AEDs. Associated with neural tube defects (spina bifida ~2–4%), hypospadias, cardiac defects, craniofacial abnormalities, and valproate syndrome. Also associated with neurodevelopmental delays (reduced IQ by ~7–10 points in offspring). SHOULD NOT BE USED in women of childbearing potential without adequate contraception. If essential, use folic acid 5mg/day from pre-conception. Pregnancy Category D — positive evidence of fetal harm.
Lactation: Caution
Excreted in breast milk (~1–10% of maternal levels). Generally considered low risk for breastfed infants. Monitor infant for hepatotoxicity and bleeding. Generally acceptable if mother requires valproate.
Top Drug Interactions
| Interacting Drug | Effect | Severity |
|---|---|---|
| Carbamazepine | Valproate inhibits metabolism of carbamazepine-10,11-epoxide (toxic metabolite) causing toxicity; carbamazepine induces valproate metabolism reducing its levels | Major |
| Lamotrigine | Valproate inhibits glucuronidation of lamotrigine — lamotrigine levels increase 2-fold; increase risk of Stevens-Johnson syndrome. Must halve lamotrigine dose when adding valproate. | Major |
| Phenytoin | Valproate displaces phenytoin from protein binding AND inhibits metabolism — initially increased free phenytoin with toxicity, then phenytoin induces valproate metabolism | Major |
| Aspirin (high dose) | Displaces valproate from albumin — increased free valproate levels; aspirin also inhibits valproate metabolism; avoid high-dose aspirin combination | Major |
| Meropenem / other carbapenems | Carbapenems dramatically reduce valproate plasma levels (50–100% reduction) — risk of seizure breakthrough. Avoid combination; use alternative antibiotic. | Major |
| Warfarin | Valproate displaces warfarin from protein binding — transient increase in INR; monitor closely | Moderate |
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Side Effects
Common
- Nausea and vomiting (especially at initiation — take with food)
- Weight gain (significant — up to 5–10 kg)
- Tremor (dose-related)
- Hair loss (telogen effluvium — often reversible)
- Drowsiness / sedation
- Diarrhea
- Appetite increase
- Hyperammonemia (with or without encephalopathy)
- Menstrual irregularities
Serious / Discontinue If
- FATAL HEPATOTOXICITY — highest risk in children <2 years on polytherapy; monitor LFTs closely in first 6 months
- Pancreatitis — potentially fatal; can occur at any time; discontinue immediately if suspected
- Thrombocytopenia — dose-related; monitor platelet counts
- Hyperammonemic encephalopathy — can occur even with normal liver enzymes (urea cycle disorders)
- PCOS-like syndrome — weight gain, hyperandrogenism, menstrual irregularity, polycystic ovaries in women
- Valproate-induced Parkinsonism (reversible on stopping)
- Teratogenicity (major — neural tube defects, cognitive impairment)
- Suicidal ideation (class-wide AED warning)
- DRESS syndrome
Contraindications
- Hepatic disease (any significant hepatic dysfunction)
- Urea cycle disorders (can cause fatal hyperammonemic encephalopathy)
- Pregnancy (especially first trimester) — SHOULD NOT be used in women of childbearing potential without effective contraception
- Known mitochondrial disease caused by POLG mutations (e.g., Alpers syndrome) — fatal hepatotoxicity
- Hypersensitivity to valproate or divalproex
Available Indian Brands
| Brand | Manufacturer | Price (approx) |
|---|---|---|
| Valparin 200mg | Torrent Pharma | ₹38/10 tablets |
| Encorate 200mg | Sun Pharma | ₹45/10 tablets |
| Valance 500mg | Zydus Cadila | ₹65/10 tablets |
| Depakote ER 500mg | Abbott India | ₹145/10 tablets |
Monitoring Required
- Serum valproate levels (therapeutic range 50–100 mcg/mL; up to 125 mcg/mL for bipolar) — check at steady state (5 days), then every 6–12 months
- LFTs (ALT, AST, bilirubin) — at baseline, monthly for 6 months, then every 6 months; ESPECIALLY in children <2 years
- CBC with platelets — at baseline and every 6 months (thrombocytopenia risk)
- Serum ammonia — if encephalopathy or confusion (hyperammonemia even with normal LFTs)
- Lipase/amylase — if abdominal pain (pancreatitis)
- Body weight — monthly (significant weight gain)
- Menstrual cycle history in women (PCOS)
- Androgen profile if PCOS suspected
- Urea cycle disorders screen before starting in children with unexplained encephalopathy
- Pregnancy test before initiation in women of childbearing age; pregnancy registry enrollment
Patient Counseling Points
- WOMEN OF CHILDBEARING AGE: Valproate causes severe birth defects — must use highly effective contraception. Discuss alternative AEDs if planning pregnancy.
- Never stop valproate suddenly — can cause dangerous seizure breakthrough or status epilepticus
- Take with food — reduces nausea significantly
- Report immediately: jaundice (yellow eyes/skin), severe abdominal pain, vomiting, loss of consciousness — signs of liver failure or pancreatitis
- Report unusual bruising or bleeding (platelet reduction)
- Hair loss may occur but is usually temporary — supplement zinc if recommended by doctor
- Weight gain is common — maintain healthy diet and exercise
- Report any confusion, unusual drowsiness (may indicate high ammonia levels)
- Regular blood tests are mandatory — cannot be skipped
- Do not take with carbapenem antibiotics (meropenem, ertapenem) — may cause seizure breakthrough
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Clinically reviewed by: Dr. Anil Sharma, MD (Neurology), DM, AIIMS New Delhi
Last reviewed: 2026-04-01
References
- Drugs.com — Valproic Acid Monograph
- CIMS India — Sodium Valproate
- FDA Prescribing Information — Depakote (AbbVie)
- Indian Epilepsy Society Guidelines 2022
- Indian National Formulary 2023
- EMA Valproate Risk Minimization Measures — 2018
- ILAE Guidelines for Treatment of Women with Epilepsy 2019
- CPIC Guideline — Valproic Acid and POLG Variants 2021