Valproate

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General

  • Type: Anticonvulsants
  • Dosage Forms: 125mg; 250mg; 500mg; 100mg/mL; 250mg/5mL; 500mg/5mL
  • Common Trade Names: Depacon, Depakene, Depakote, Depakote ER. Depakote Sprinkles, Stavzor

Adult Dosing

Seizures

  • Oral (max 60mg/kg/d)
    • Simple/complex absence: Initial 15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
    • Complex partial: Initial 10-15mg/kg/d; increase 5-10mg/kg/d at weekly until therapeutic
      • Extended release formulation given once daily
  • IV: same dose as oral, administered as 60min infusion

Status epilepticus, refractory

  • IV: Loading 15-20mg/kg administered at 20mg/min
    • Maintenance: 1-5mg/kg/hr

Bipolar disorder, manic episode

  • Oral: Depakote Stavzor 750mg/d or Depakote ER 25mg/kg/d qday

Migraine prophlyaxis

  • Oral: Depakote, Stavzor 250mg BID or Depakote ER 500mg qday

Pediatric Dosing

  • Same as adult dosing
  • Avoid extended release formulation in children <10yr

Special Populations

  • Pregnancy Rating: X
  • Lactation: Use with caution. Excreted in breast milk.
  • Renal Dosing: No adjustment
  • Hepatic Dosing
    • Mild-mod impairment: Not recommended
    • Severe impairment: Contraindicated

Contraindications

  • Allergy to class/drug
  • Severe hepatic impairment
  • Pregnancy
  • Urea cycle disorders
  • Mitochondrial disorders

Adverse Reactions

Serious

  • Hepatotoxicity
  • Congenital malformation: neural tube defect
  • Pancreatitis

Common

Toxicity

  • Potential use for early IV L-carnitine to reduce hepatotoxicity
  • 100mg/kg IV once, followed by 50mg/kg (max 3 g per dose) q8hrs until ammonia levels normalize[1]

Pharmacology

  • Half-life:
    • Children >2mo: 7-13 hours
    • Adult: 9-19 hours
  • Metabolism: Hepatic glucuronide conjugation and mitochondrial beta-oxidation
  • Excretion: Urine
  • Mechanism of Action: Increases availability and enhances action of GABA

See Also

References

  1. Perott J et al. L-carnitine for acute valproic acid overdose: a systematic review of published cases. Ann Pharmacother. 2010 Jul-Aug;44(7-8):1287-93. doi: 10.1345/aph.1P135. Epub 2010 Jun 29.