Sodium Valproate

1. Introduction

Sodium valproate is an antiepileptic drug (AED) used to manage various types of seizures, bipolar disorder, and migraine prophylaxis. It works by enhancing the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, stabilising electrical activity in the brain.

2. Indications

  • Epilepsy:
    • Generalised seizures (tonic-clonic, absence, myoclonic).
    • Focal seizures.
    • Mixed seizure types.
  • Bipolar Disorder:
    • Treatment of manic episodes and prevention of mood swings.
  • Migraine Prophylaxis:
    • Prevention of recurrent migraines.

3. Dosage

Adults:

  • Epilepsy: Start with 600 mg/day, divided into 2–3 doses, and increase by 200 mg/day at 3-day intervals as needed.
    • Typical maintenance dose: 1,000–2,000 mg/day.
    • Maximum dose: 2,500 mg/day.
  • Bipolar Disorder: Start with 750 mg/day, divided into 2–3 doses. Adjust based on response.
    • Typical maintenance dose: 1,000–2,000 mg/day.
  • Migraine Prophylaxis: 300–600 mg/day in divided doses.

Children (Epilepsy):

  • 20 mg/kg/day initially, divided into 2–3 doses. Adjust as needed.
    • Maximum dose: 35 mg/kg/day.

Elderly:

  • Start with the lowest effective dose, as elimination may be slower.

Renal or Hepatic Impairment:

  • Avoid in severe hepatic impairment. Use cautiously with dose adjustments in renal impairment.

4. Administration

  • Take orally with or after food to reduce gastrointestinal upset.
  • Extended-release formulations should be swallowed whole and not crushed or chewed.

5. Forms Available

  • Tablets: 200 mg, 500 mg (immediate and extended-release).
  • Oral solution: 200 mg/5 mL.
  • Injection: 400 mg/4 mL (for IV use).

6. Side Effects

6.1 Common Side Effects:

  • Nausea
  • Vomiting
  • Tremor
  • Weight gain
  • Hair thinning

6.2 Less Common Side Effects:

  • Drowsiness
  • Dizziness
  • Abdominal pain
  • Diarrhoea

6.3 Rare but Serious Side Effects:

  • Hepatotoxicity (especially in children <2 years or with predisposing conditions).
  • Pancreatitis (can be life-threatening).
  • Thrombocytopenia (low platelet count).
  • Hyperammonaemia (leading to encephalopathy).

7. Warnings

  • Hepatotoxicity: Avoid use in children under 2 years or those with metabolic disorders due to a higher risk of liver failure. Monitor liver function regularly.
  • Pancreatitis: Discontinue immediately if symptoms (severe abdominal pain, vomiting) occur.
  • Pregnancy Risks: Sodium valproate can cause significant teratogenic effects, including neural tube defects. Avoid use in pregnancy unless no safer alternative is available.
  • Suicidal Thoughts: Monitor for behavioural changes or suicidal ideation.

8. Precautions

  • Use cautiously in patients with liver disease, blood disorders, or a history of metabolic disorders.
  • Avoid abrupt discontinuation to prevent seizure exacerbation.
  • Regularly monitor liver function tests (LFTs), complete blood count (CBC), and serum ammonia levels.

9. Interactions

  • Other AEDs (e.g., lamotrigine): Increased risk of side effects (e.g., skin rash) and altered drug levels.
  • Aspirin and NSAIDs: Increased risk of bleeding due to platelet dysfunction.
  • Warfarin: Enhanced anticoagulant effect; monitor INR closely.
  • Carbapenem Antibiotics (e.g., meropenem): May significantly reduce sodium valproate levels.

10. Monitoring Parameters

  • Liver function tests (ALT, AST) at baseline and periodically.
  • Complete blood count (platelets, WBC) at baseline and during treatment.
  • Serum ammonia levels if symptoms of encephalopathy occur.
  • Plasma drug levels for therapeutic monitoring, particularly in children or when adjusting doses.

11. Use in Children

  • Approved for use in epilepsy in children, but use cautiously in children under 2 years due to a higher risk of hepatotoxicity.
  • Dose based on body weight (20–30 mg/kg/day).

12. Use in Pregnancy

  • Category D/X (depending on indication): Sodium valproate is contraindicated in pregnancy unless no safer alternative is available. It is associated with significant risks, including neural tube defects, developmental delays, and cognitive impairment in the foetus.
  • Women of childbearing age must use effective contraception and discuss risks with their healthcare provider.

13. Use in Elderly

  • Use cautiously in elderly patients, starting with the lowest effective dose. Monitor for sedation and altered drug clearance due to age-related changes.

14. Use in Kidney Disease

  • Use cautiously with dose adjustments based on clinical response and drug levels.

15. Use in Liver Disease

  • Avoid use in patients with severe hepatic impairment. Monitor liver function closely in all patients, especially during the first 6 months of treatment.

16. Patient Counselling Points

  • Take sodium valproate regularly as prescribed. Do not skip doses or stop abruptly.
  • Inform your doctor if you experience symptoms of liver damage (e.g., yellowing of the skin, dark urine) or pancreatitis (e.g., severe abdominal pain).
  • Women of childbearing age should use effective contraception and consult their doctor before planning a pregnancy.
  • Avoid alcohol, as it may worsen side effects like drowsiness or dizziness.
  • Regular blood tests may be needed to monitor your treatment safely.

17. Table of Brand Names, Manufacturer, and Prices in USD

Brand NameManufacturerStrength/Dosage FormPrice (USD)
EpilimSanofi500 mg Tablet (ER)$30 (30 tablets)
DepakoteAbbVie250 mg Tablet$25 (30 tablets)
Generic Sodium ValproateVarious200 mg Tablet$15 (30 tablets)

18. 15 FAQs (Frequently Asked Questions)

1. What is Sodium Valproate used for?
It is used to treat epilepsy, bipolar disorder, and prevent migraines.

2. How does Sodium Valproate work?
It increases GABA activity in the brain, stabilising electrical activity and reducing seizures or mood swings.

3. Can Sodium Valproate be used in pregnancy?
No, it is contraindicated unless no safer alternative exists due to significant teratogenic risks.

4. Can Sodium Valproate cause weight gain?
Yes, weight gain is a common side effect.

5. How long does Sodium Valproate take to work?
Effects on seizures or mood may take several days to weeks.

6. Can Sodium Valproate cause liver damage?
Yes, it may cause hepatotoxicity, especially in young children or those with underlying conditions.

7. Can I stop Sodium Valproate suddenly?
No, abrupt discontinuation can worsen seizures. Consult your doctor for a tapering plan.

8. Does Sodium Valproate interact with other medications?
Yes, it interacts with other antiepileptics, anticoagulants, and carbapenem antibiotics.

9. Can Sodium Valproate cause pancreatitis?
Yes, though rare, it can cause life-threatening pancreatitis.

10. What monitoring is required during Sodium Valproate therapy?
Liver function, blood counts, and serum ammonia levels should be monitored regularly.

11. Can children use Sodium Valproate?
Yes, it is approved for epilepsy in children, but with caution in those under 2 years.

12. Can Sodium Valproate cause drowsiness?
Yes, drowsiness is a common side effect, particularly during dose adjustments.

13. Is Sodium Valproate safe for long-term use?
Yes, but regular monitoring is essential to manage potential side effects.

14. How should Sodium Valproate be stored?
Store at room temperature, away from moisture and heat.

15. Can Sodium Valproate be taken with food?
Yes, taking it with food may reduce gastrointestinal side effects.