Clinical Information

Valproic acid (valproate, Depakote, or Depakene) is an effective medication for absence seizures, generalized tonic-clonic seizures, and partial seizures, when administered alone or in conjunction with other antiepileptic agents.

Valproic acid is initially dosed at 15 mg/kg/day, with dosage increases over time to a maximum of 60 mg/kg/day. The volume of distribution of valproic acid is 0.2 L/kg, and its half-life is 10 to 14 hours in adults but is shorter in children. It is approximately 90% protein bound.

Hepatic failure and a Reyes-like syndrome associated with administration of valproic acid at therapeutic levels have been reported. Careful monitoring of liver function during the first 6 months of therapy is required. Major side effects such as central nervous system depression, thrombocytopenia, and hepatic dysfunction are likely to be experienced if the peak level is regularly above 125 mcg/mL.

Analysis of free valproic acid levels may be useful in delineating the cause of toxicity when the total concentration is not excessive.

Valproic acid exhibits substantial effects on the pharmacology of phenytoin, whereas phenytoin exhibits only a limited effect on valproic acid. This is due to the relative abundance of the 2 drugs in the body. Valproic acid is present at a 2- to 3-fold mass excess and a 5- to 7-fold molar excess.