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
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
- 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
- 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
- ↑ 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.