Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inducers may decrease the plasma concentrations of tucatinib, which is primarily metabolized by CYP450 2C8 and to a lesser extent by CYP450 3A4. When rifampin (600 mg once daily), a potent CYP450 3A4 and moderate CYP450 2C8 inducer, was administered with a single tucatinib dose of 300 mg, tucatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 50%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of tucatinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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.