Serum
phenytoin levels can be markedly reduced by
rifampicin (clearance doubled in one study). If
rifampicin is given with isoniazid,
phenytoin levels may fall in patients who are fast acetylators of isoniazid, but may occasionally rise in those who are slow acetylators. Fosphenytoin, a prodrug of
phenytoin, may interact similarly.
It is unlikely that the acetylator status of the patient will be known. Therefore monitor
phenytoin levels and adjust the dose accordingly.