Valproic acid: interaction with other anticonvulsant drugs.

The interaction of valproic acid and other antiepileptic drugs was studied in 25 patients for 5 to 9 months. Clinical evaluations, seizure records, and antiepileptic drug levels were followed regularly. Eleven of the 13 patients required a reduced phenobarbital dose when concurrently treated with valproic acid. This reduction was prompted by sedation. An average dose reduction of 46 percent resulted in an average serum phenobarbital decrease of 15 percent. Ten of 15 patients had decreased phenytoin concentrations during concurrent administration with valproic acid. No definitive conclusion was reached about other antiepileptic drugs. Decreased phenobarbital excretion because of urine acidification and displacement of phenytoin from protein binding sites may account for the observations. Careful monitoring of anticonvulsant levels is required in anticipation of the documented interactions.