A MAJOR STEP IN ROFLUMILAST METABOLISM IS THE N-OXIDATION OF ROFLUMILAST TO ROFLUMILAST N-OXIDE BY CYP3A4 AND CYP1A2.
DRUGS THAT INDUCE CYTOCHROME P450 (CYP) ENZYMES
STRONG CYP450 ENZYME INDUCERS E.G., RIFAMPICIN, PHENOBARBITAL, CARBAMAZEPINE, AND PHENYTOIN DECREASE SYSTEMIC EXPOSURE TO ROFLUMILAST AND MAY REDUCE THE THERAPEUTIC EFFECTIVENESS OF DALIRESP.
THE CO-ADMINISTRATION OF ROFLUMILAST (500 MCG) WITH CYP3A4 INHIBITORS OR DUAL INHIBITORS THAT INHIBIT BOTH CYP3A4 AND CYP1A2 SIMULTANEOUSLY (E.G., ERYTHROMYCIN, KETOCONAZOLE, FLUVOXAMINE, ENOXACIN, CIMETIDINE) MAY INCREASE ROFLUMILAST SYSTEMIC EXPOSURE AND MAY RESULT IN INCREASED ADVERSE REACTIONS.
THE CO-ADMINISTRATION OF ROFLUMILAST (500 MCG) WITH ORAL CONTRACEPTIVES CONTAINING GESTODENE AND ETHINYL ESTRADIOL MAY INCREASE ROFLUMILAST SYSTEMIC EXPOSURE AND MAY RESULT IN INCREASED SIDE EFFECTS.