Pharm

Valproate

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Valproate, Valproic Acid, Depakote, Depakene

  • See Also
  1. Valproic Acid Toxicity
  • Indications
  1. Generalized Tonic Clonic Seizures
  2. Absence Seizures
  3. Myoclonic Seizures
  4. Simple Partial Seizures
  5. Complex Partial Seizures
  6. Migraine Headache Prophylaxis
  7. Bipolar Disorder (mood stabilizer)
  • Contraindications
  1. Hepatic dysfunction
  2. Pregnancy
  3. Urea cycle disorder
  • Adverse Effects
  • Dose related
  1. Nausea and Vomiting
  2. Tremor
  3. Ataxia
  4. Diarrhea
  5. Lethargy or sedation
  6. Mild Liver Function Test abnormalities (AST, ALT)
  7. Weight gain
  • Adverse Effects
  1. Pancreatitis
  2. Alopecia
    1. Centrum A-Zinc daily prevents associated Hair Loss
  3. Thrombocytopenia
  4. Leukopenia
  5. Stevens-Johnson Syndrome
  6. Osteoporosis
  7. Hepatic dysfunction (in rare cases, may be fatal)
  • Pharmacokinetics
  1. Rapidly absorbed
    1. Absorption period prolonged with extended release preparations
  2. High Protein Binding (decreased in Overdose)
  3. Hepatic metabolism
    1. Glucoronidation
    2. Beta and omega oxidation
  • Dosing
  • Adults
  1. Seizure Disorder
    1. Initial: 10-15 mg/kg/day divided daily to three times daily
    2. Increase in 5-10 mg/kg/day increments weekly
    3. Target dose: 30-60 mg/kg/day to 1000-2500 mg/day
      1. Divide regular and delayed release dosing two to four times daily
      2. Extended release may be dosed once daily
  2. Migraine Headache Prophylaxis
    1. Initial
      1. Depakote ER 500 mg orally daily for 7 days
      2. Depakote delayed release 250 mg orally twice daily
    2. May increase to 1000 mg/day
  3. Bipolar Disorder
    1. Loading dose in acute mania: 15-20 mg/kg
    2. Starting dose without load: 500 to 750 mg/day in divided dosing
    3. Titrate every 2-3 days as tolerated to serum Valproic Acid level of 50 to 125 mcg/ml
    4. Target dose: 1000 to 3000 mg daily in divided doses
  • Drug Interactions
  1. Numerous Drug Interactions
  • Toxicity
  1. Large therapeutic window
  2. See Valproic Acid Toxicity
  • Monitoring
  1. Serum Valproate level
    1. Initial: Every 1-2 weeks
    2. Later: Every 3-6 months
  2. Other routine monitoring
    1. Obtain monthly for 2 months and then every 3 to 12 months
    2. Complete Blood Count
    3. Liver Function Tests
  • Pregnancy Risk
  1. Class D
  • History
  1. Synthesized in 1882, but not recognized as an anticonvulsant until 1963
  • References
  1. Sun (2017) Crit Dec Emerg Med 31(1): 24