Carbamazepine increases phenytoin serum concentration and reduces phenytoin clearance.

ABSTRACT

Addition of carbamazepine to phenytoin monotherapy resulted in the following significant (p less than 0.05) changes (1) increased mean phenytoin serum concentration; (2) decreased phenytoin clearance, due to decreased production of phenytoin dihydrodiol and p-hydroxyphenyl-phenylhydantoin; (3) increased phenytoin elimination half-life; and (4) increased drug-related toxicity. Close monitoring is required after addition of carbamazepine to phenytoin.