1. Introduction
Valproic acid (also known as sodium valproate or divalproex sodium) is a broad-spectrum anticonvulsant and mood stabiliser used primarily for epilepsy, bipolar disorder, and migraine prophylaxis. It works by increasing gamma-aminobutyric acid (GABA) activity, stabilising neuronal excitability.
2. Indications
- Epilepsy:
- Generalised seizures (tonic-clonic, absence, myoclonic)
- Focal seizures
- Bipolar Disorder:
- Acute mania and long-term mood stabilisation
- Migraine Prophylaxis
- Off-Label Uses:
- Neuropathic pain
- Schizoaffective disorder
- Aggression in dementia
3. Dosage
Adults:
- Epilepsy:
- Initial dose: 10–15 mg/kg/day, increasing by 5–10 mg/kg every week
- Maintenance dose: 750–2,000 mg/day in divided doses
- Max dose: 60 mg/kg/day
- Bipolar Disorder:
- Acute mania: 750 mg/day, increased to 1,000–2,500 mg/day
- Maintenance: 500–2,000 mg/day
- Migraine Prevention:
- 500–1,000 mg/day in divided doses
Children:
- Epilepsy:
- 10–15 mg/kg/day, increasing by 5–10 mg/kg weekly
- Maintenance dose: 15–30 mg/kg/day (max 60 mg/kg/day)
Elderly:
- Use lower initial doses due to increased sensitivity.
Renal Impairment:
- No major dose adjustment, but monitor for toxicity.
Hepatic Impairment:
- Avoid in severe liver disease due to risk of fatal hepatotoxicity.
4. Administration
- Take with food to reduce stomach upset.
- Do not crush or chew enteric-coated or extended-release tablets.
- Monitor drug levels in epilepsy patients (therapeutic range: 50–100 mcg/mL).
5. Forms Available
- Tablets: 250 mg, 500 mg (immediate or extended-release)
- Capsules: 250 mg
- Oral Solution/Syrup: 250 mg/5 mL
- IV Injection: 100 mg/mL
6. Side Effects
6.1 Common Side Effects:
- Nausea, vomiting
- Tremor
- Weight gain
- Hair thinning (reversible)
- Fatigue
6.2 Less Common Side Effects:
- Dizziness
- Blurred vision
- Menstrual irregularities
6.3 Rare but Serious Side Effects:
- Hepatotoxicity (Liver failure, especially in children <2 years)
- Pancreatitis (Severe abdominal pain, nausea, vomiting)
- Hyperammonaemia (Confusion, lethargy, vomiting)
- Blood dyscrasias (Thrombocytopenia, leucopenia)
- Teratogenicity (Neural tube defects, cognitive impairment in pregnancy)
7. Warnings
- Liver Toxicity: Monitor liver function (ALT, AST, bilirubin) before starting and periodically.
- Pancreatitis Risk: Stop immediately if severe abdominal pain occurs.
- Suicidal Thoughts: Monitor for mood changes or self-harm risk.
- Weight Gain & Metabolic Effects: Encourage lifestyle modifications.
- Risk of PCOS: Long-term use may cause polycystic ovarian syndrome (PCOS).
8. Precautions
- Avoid alcohol due to CNS depression risk.
- Caution in elderly patients due to increased fall risk.
- Monitor ammonia levels if signs of encephalopathy occur.
- Avoid abrupt discontinuation to prevent seizure relapse.
9. Interactions
- Lamotrigine: Increased risk of serious rash (Stevens-Johnson syndrome).
- Warfarin & Aspirin: Increased bleeding risk.
- Carbamazepine & Phenytoin: May alter valproic acid levels.
- Topiramate: Increased risk of hyperammonaemia & encephalopathy.
10. Monitoring Parameters
- Liver function tests (LFTs) every 6 months.
- Serum valproic acid levels (target: 50–100 mcg/mL).
- Platelet count & coagulation profile.
- Weight & metabolic parameters.
11. Use in Children
- Avoid in children <2 years due to high risk of hepatotoxicity.
- Safe for paediatric epilepsy, but requires careful dose monitoring.
12. Use in Pregnancy
- Category X (for migraine prophylaxis); Category D (for epilepsy/bipolar disorder).
- High risk of neural tube defects (spina bifida) – avoid in women of childbearing age unless absolutely necessary.
- If used, supplement with high-dose folic acid (5 mg/day).
13. Use in Elderly
- Start with lower doses due to increased sensitivity.
- Monitor for falls, sedation, and liver toxicity.
14. Use in Kidney Disease
- No major dose adjustments needed, but monitor for drug accumulation.
15. Use in Liver Disease
- Contraindicated in severe hepatic impairment.
- Monitor liver enzymes regularly in mild cases.
16. Patient Counselling Points
- Take with food to reduce stomach irritation.
- Do not stop suddenly—taper dose if discontinuing.
- Monitor for signs of liver or pancreas problems (abdominal pain, nausea, jaundice).
- Report unusual bruising or bleeding to your doctor.
- Avoid alcohol and CNS depressants.
17. Table of Brand Names, Manufacturer, and Prices in USD
Brand Name | Manufacturer | Strength/Dosage Form | Price (USD) |
---|---|---|---|
Depakote | AbbVie | 250 mg, 500 mg Tablets | $100 (30 tabs) |
Epilim | Sanofi | 200 mg, 500 mg Tablets | $80 (30 tabs) |
Generic Valproate | Various | 250 mg, 500 mg Tablets | $40 (30 tabs) |
Depakene | Bausch Health | 250 mg Capsules | $60 (30 caps) |
18. 15 FAQs (Frequently Asked Questions)
1. What is Valproic Acid used for?
It is used for epilepsy, bipolar disorder, and migraine prevention.
2. How does Valproic Acid work?
It increases GABA activity, stabilising brain excitability.
3. How long does Valproic Acid take to work?
- Seizures: 1–2 weeks
- Bipolar disorder: 2–4 weeks
- Migraines: 4–6 weeks
4. Can Valproic Acid cause weight gain?
Yes, weight gain is common; exercise and diet modifications may help.
5. Can I drink alcohol with Valproic Acid?
No, alcohol increases sedation and liver toxicity.
6. Can Valproic Acid cause hair loss?
Yes, mild hair thinning is reversible after stopping.
7. Does Valproic Acid affect contraception?
It may reduce the effectiveness of oral contraceptives.
8. Can Valproic Acid cause liver damage?
Yes, it can cause hepatotoxicity, especially in children under 2 years.
9. Can I stop Valproic Acid suddenly?
No, sudden discontinuation can trigger seizures or mood relapse.
10. Does Valproic Acid affect memory?
It may cause brain fog or cognitive dulling in some patients.