Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentration and pharmacologic effects of ritlecitinib. The proposed mechanism is increased clearance of ritlecitinib due to induction of the CYP450 3A4 isoenzyme, one of the pathways of elimination of ritlecitinib. When a single 50 mg dose of ritlecitinib was administered in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 8 days), the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of ritlecitinib decreased by approximately 25% and 44%, respectively, compared to ritlecitinib administered alone. Data are not available of other, less potent inducers.

MANAGEMENT: Caution is advised when ritlecitinib is used with CYP450 3A4 inducers. The possibility of diminished therapeutic effects should be considered.

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.