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

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>