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

References

<UptoDate, epocrates>

Authors

Kristina Shigyo, Claire, Neil Young, Ross Donaldson, Daniel Ostermayer