Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of axitinib, which is primarily metabolized by the isoenzyme. In a study of 40 healthy, nonsmoking, male volunteers, administration of a single 5 mg dose of axitinib on day 8 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg/day for 9 days) resulted in a 71% decrease in mean axitinib peak plasma concentration (Cmax) and 79% decrease in mean systemic exposure. The extent to which other, less potent inducers of CYP450 3A4 may interact with axitinib is unknown.

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

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.

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.