Drug Interaction Report

MONITOR: Coadministration with CYP450 1A2 inhibitors or dual CYP450 1A2/3A4 inhibitors may increase the systemic exposure to roflumilast and its pharmacologically active N-oxide metabolite. In drug interaction studies, the total exposure to roflumilast and roflumilast N-oxide increased by 25%, 47% and 59% with the CYP450 1A2 inhibitor enoxacin and the dual CYP450 1A2/3A4 inhibitors cimetidine and fluvoxamine, respectively.

MANAGEMENT: Treatment with roflumilast should be re-evaluated if an interaction is suspected and persistent intolerability occurs. Patients should be advised to contact their physician if they experience increased frequency and/or severity of side effects such as diarrhea, nausea, abdominal pain, weight loss, and headache.

Food intake does not affect the total exposure to roflumilast and its pharmacologically active N-oxide metabolite, but delays the time to maximum concentration (Tmax) of roflumilast by one hour and reduces its peak plasma concentration (Cmax) by approximately 40%. The Tmax and Cmax of
roflumilast N-oxide are unaffected. Roflumilast may be taken with or without food.