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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.