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: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

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.