Valproate

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
• Mania
  • 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

• Headache, drowsiness, dizziness, insomnia, nervousness, pain
• Alopecia
• Nausea, vomiting, diarrhea, abdominal pain, anorexia
• Thrombocytopenia
• Infection
• Tremor, weakness
• Diplopia, visual disturbance
• Flu-like symptoms

Toxicity

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

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

• Seizure

Sources

• UpToDate