Drug Interaction Report

MONITOR: Coadministration with pitolisant may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Pitolisant is a borderline/weak inducer of CYP450 3A4. When studied with midazolam, a probe substrate for CYP450 3A4, pitolisant was found to reduce midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by less than 25%.

MANAGEMENT: Caution is advised when pitolisant is used in combination with sensitive CYP450 3A4 substrates. Clinical and laboratory monitoring may be appropriate whenever pitolisant is added to or withdrawn from therapy, and dosage adjustments made if necessary. It may be advisable to avoid concomitant use of pitolisant and CYP450 3A4 substrates with a narrow therapeutic index, if possible.

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.