Valproic acid
Administration
- Type: Anticonvulsant
- Dosage Forms: 250mg, 250/5 mL
- Routes of Administration: Oral, IV
- Common Trade Names: Depacon; Depakene; Depakote; Depakote ER; Depakote Sprinkles; Stavzor
Adult Dosing
- Complex partial seizures: 30-60mg/kg/day PO (divided bid-tid)
- Start: 10-15mg/kg/day PO divided QD-tid
- Increase by 5-10mg/kg/day q7 days
- Max: 60mg/kg/day
- Decrease start dose and titrate slowly in elderly patients
- Adjust dose based on treatment response and serum levels
- Divide doses >250mg/day
- Do not cut/crush/chew with outpen caps
- Taper dose gradually to discontinue
- Total daily IV dose should equal total oral daily dose
- Administer IV dose as a 60-minute infusion (≤20mg/minute)
- Absence seizures, simple and complex: 30-60mg/kg/day PO (divided bid-tid)
- Start: 15mg/kg/day PO divided QD-tid, increase by 5-10mg/kg/day every 7 days
- Max: 60mg/kg/day
- Bipolar disorder, acute mania: 250-500mg PO tid
- Start: 250mg PO tid, may increase dose rapidly to lowest effective dose
- Max: 60mg/kg/day
- Decrease start dose and titrate slowly in elderly patients
- Migraine headache prophylaxis: 250-500mg PO bid
- Start: 250mg PO bid
- Status epilepticus (off-label use): IV loading dose: 20 to 40mg/kg
- Administer at rate of 3 to 6mg/kg/min
- May give an additional dose of 20mg/kg 10 minutes after the loading infusion
Pediatric Dosing
- Partial seizures, complex: 30-60mg/kg/day PO divided bid-tid
- Start: 10-15mg/kg/day PO divided QD-tid,
- Increase by 5-10mg/kg/day q7 days; Max: 60mg/kg/day;
- Adjust dose based on treatment response and serum levels
- Not recommended under age 10
- Absence seizures, simple and complex: 30-60mg/kg/day PO divided bid-tid
- Start: 15mg/kg/day PO divided QD-tid
- Increase by 5-10mg/kg/day q7 days
- Max: 60mg/kg/day
- Not recommended under age 10
Special Populations
- Pregnancy Risk Factor: X (migraine prophylaxis)/D (all other indications)
Renal Dosing
- No adjustment necessary though may cause levels to be misleading
Hepatic Dosing
- Mild to moderate impairment: Not recommended for use in hepatic disease; clearance is decreased with liver impairment
- Severe impairment: Use is contraindicated.
Contraindications
- Hypersensitivity to valproic acid
- Hepatic disease
- Hepatic impairment, significant
- Urea cycle disorders
- Mitochondrial disorder, POLG-related
- Pregnancy (migraine headache prophylaxis use)
Adverse Reactions
Serious
- Hepatotoxicity
- Pancreatitis
- SIADH
- Hyponatremia
- Pancytopenia
- Thrombocytopenia
- Drug reaction with eosinophilia and systemic symptoms
- Hyperammonemia
- Hypothermia
- Myelosuppression
- Aplastic anemia
- Bleeding
- Erythema multiforme/SJS/TEN
Common
- Headache
- Nausea/vomiting
- Asthenia
- Somnolence
- Thrombocytopenia
- Dyspepsia
- Dizziness
Pharmacology
- Half-life: 16 hrs
- Metabolism: CYP450
- Excretion: Urine
Mechanism of Action
- Increases GABA effects, may inhibit glutamate/NMDA receptor-mediated neuronal excitation
See also
References
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