PHENYTOIN AND RIFAMPICIN (RIFAMPIN)

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.