Usage
- Sodium Valproate is prescribed for the treatment of various types of epileptic seizures (generalized tonic-clonic, absence, myoclonic, and partial seizures), bipolar disorder (for managing manic episodes and preventing relapse), and migraine prophylaxis.
- Pharmacological Classification: Anticonvulsant, mood stabilizer.
- Mechanism of Action: Sodium valproate’s precise mechanism of action is not fully understood, but it is thought to involve multiple mechanisms including increasing brain levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, blocking voltage-gated sodium channels, and affecting potassium channels, thereby reducing neuronal excitability.
Alternate Names
- Valproic acid
- Valproate sodium
- Brand Names:
- Epilim
- Depakene
- Depakote
- Stavzor
- Convulex
How It Works
- Pharmacodynamics: Sodium valproate exerts its anticonvulsant effect by enhancing GABAergic inhibition in the brain. It also modulates voltage-gated sodium and potassium channels, decreasing neuronal excitability and suppressing seizure activity. In bipolar disorder, it stabilizes mood, potentially by affecting inositol metabolism and modulating intracellular signaling pathways.
- Pharmacokinetics: Sodium valproate is well-absorbed orally. It is highly protein-bound (primarily to albumin) and metabolized extensively in the liver via glucuronidation and mitochondrial beta-oxidation. It has a relatively short half-life (9-16 hours), requiring multiple daily doses. Elimination is primarily renal.
- Mode of Action: Increases GABA levels, blocks sodium channels, and affects potassium channels, reducing neuronal excitability.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Enhances GABAergic activity, may inhibit GABA transaminase, and modulates sodium and potassium channels.
- Elimination Pathways: Primarily renal excretion of metabolites. Some hepatic metabolism via CYP enzymes.
Dosage
Standard Dosage
Adults:
- Epilepsy/Bipolar Disorder: Initial 600mg daily, increased by 200mg every 3 days until seizure control or mood stabilization is achieved. Usual maintenance dose: 1000-2000mg daily (20-30 mg/kg/day), up to a maximum of 2500mg/day in divided doses.
- Migraine Prophylaxis: 200-400mg twice daily.
Children:
- Epilepsy/Bipolar Disorder: Initial 10-15mg/kg/day, increased by 5-10 mg/kg weekly until optimal response. Maximum 60 mg/kg/day. Use syrup for children under 20 kg. For children over 20kg, start with 400mg daily, irrespective of weight, and increase until control is achieved, typically within the range of 20-30mg/kg body weight per day.
- Pediatric Safety Considerations: Monitor liver function, especially in children under 2 years old.
Special Cases:
- Elderly Patients: Start with lower doses and titrate slowly. Monitor for adverse effects like somnolence, dehydration, and nutritional status.
- Patients with Renal Impairment: Dose reduction may be necessary. Monitor closely.
- Patients with Hepatic Dysfunction: Contraindicated in severe liver disease. Use with caution in mild to moderate hepatic impairment and adjust dosage based on clinical monitoring.
- Patients with Comorbid Conditions: Consider interactions with other medications and adjust dosage accordingly.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Intravenous administration may be used if oral administration is not feasible, at 10-15 mg/kg/day, with adjustments as needed. Switch to oral administration as soon as possible.
- Emergency Situations (e.g., status epilepticus): Intravenous administration of 10-15 mg/kg/day, infused slowly over 1 hour. Maximum dose 60mg/kg/day.
Dosage Adjustments
- Adjust dosage based on patient response, tolerability, and plasma levels (therapeutic range: 50-100 mcg/mL).
- Consider renal/hepatic function, age, concomitant medications, and other individual factors.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea
- Tremor
- Weight gain
- Hair thinning or loss
- Drowsiness, dizziness
Rare but Serious Side Effects
- Pancreatitis
- Hepatotoxicity (liver damage)
- Thrombocytopenia (low platelet count)
- Encephalopathy (brain dysfunction)
- Hyperammonemia (elevated ammonia levels)
- Suicidal thoughts
Long-Term Effects
- Polycystic ovary syndrome
- Osteoporosis (reduced bone density)
Adverse Drug Reactions (ADR)
- Hepatic failure
- Severe thrombocytopenia
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
Contraindications
- Hypersensitivity to valproate
- Liver disease (severe)
- Urea cycle disorders
- Mitochondrial disorders caused by POLG mutations (especially Alpers-Huttenlocher Syndrome)
- Pregnancy (especially for migraine or bipolar disorder; use with extreme caution in epilepsy if no other suitable alternative is available, within a pregnancy prevention program).
Drug Interactions
- Enzyme-inducing drugs (e.g., carbamazepine, phenytoin, phenobarbital, rifampicin): Decrease valproate levels.
- Enzyme-inhibiting drugs (e.g., felbamate, cimetidine, erythromycin): Increase valproate levels.
- Salicylates: Increased risk of hepatotoxicity.
- Lamotrigine: Increased risk of lamotrigine-induced rash.
- Warfarin: Increased risk of bleeding.
- Other anticonvulsants: Alterations in serum levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D (Australia); X (US- for migraine and bipolar disorder); not assigned (US-for Epilepsy)
- Fetal Risks: Neural tube defects (e.g., spina bifida), congenital malformations, developmental delays, lower IQ, autism spectrum disorder.
- Breastfeeding: Small amounts are excreted in breast milk. Monitor infant for potential side effects. If valproate is essential, discuss benefits and risks with the mother.
Popular Combinations
- Lamotrigine
- Levetiracetam
- Carbamazepine (with caution due to interaction)
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sodium Valproate?
A: (See Dosage section above for details)
Q2: What are the common side effects of Sodium Valproate?
A: Nausea, vomiting, tremor, weight gain, hair loss, drowsiness.
Q3: What are the serious side effects of sodium valproate?
A: Liver toxicity, pancreatitis, thrombocytopenia, encephalopathy, hyperammonemia, suicidal thoughts.
Q4: Can Sodium Valproate be used during pregnancy?
A: Contraindicated for migraine and bipolar disorder during pregnancy. Use with extreme caution in epilepsy only if other options are ineffective, within a pregnancy prevention program, due to significant risks of birth defects and developmental problems.
Q5: What are the drug interactions with Sodium Valproate?
A: Interacts with enzyme-inducing and inhibiting drugs (carbamazepine, phenytoin, phenobarbital, felbamate, erythromycin, etc.), salicylates, lamotrigine, warfarin, and other anticonvulsants.
A: Metabolized primarily in the liver, mainly through glucuronidation and beta-oxidation, and eliminated primarily by the kidneys.
Q7: What monitoring parameters are essential for patients on Sodium Valproate?
A: Liver function tests, complete blood count (including platelets), serum ammonia levels (if indicated), valproate serum levels (if indicated).
Q8: Can sodium valproate be given intravenously?
A: Yes, Sodium valproate can be administered intravenously when oral administration is not feasible.
Q9: What is the mechanism of action of sodium valproate in bipolar disorder?
A: The exact mechanism in bipolar disorder is not fully understood, but it is believed to involve modulating GABA levels and intracellular signaling pathways.
Q10: Is sodium valproate safe to use in patients with kidney disease?
A: Dose adjustment may be necessary in patients with renal impairment, and they should be monitored closely. It is contraindicated in patients with severe renal disease.
