Drug Interaction Report

GENERALLY AVOID: Coadministration with potent and moderate inducers of CYP450 3A4 may significantly 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: Concomitant use of axitinib with potent CYP450 3A4 inducers such as apalutamide, carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided. Although pharmacokinetic data are lacking, the manufacturer recommends that moderate CYP450 3A4 inducers should also be avoided if possible, including but not limited to bosentan, cenobamate, dabrafenib, dexamethasone, efavirenz, etravirine, lorlatinib, modafinil, nafcillin, pexidartinib, and sotorasib.

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.