<p>A major step in Roflumilast metabolism is the N-oxidation of Roflumilast to Roflumilast N-oxide by CYP3A4 and CYP1A2. Therefore, the use of strong cytochrome P450 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin) with Roflumilast is not recommended. The co-administration of Roflumilast 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 with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased side effects.</p>