In vitro studies have found that the active
metabolite of
leflunomide (A771726) is an inhibitor of CYP2C9, the isoenzyme concerned with the
metabolism of
phenytoin and fosphenytoin.
Although no cases of
phenytoin toxicity appear to have been reported as a result of this interaction, caution would be advisable on concurrent use, especially as
leflunomide has, in practice, been seen to inhibit the
metabolism of other CYP2C9 substrates.