Drug Interaction Report

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent and moderate CYP450 3A inducers may significantly decrease the plasma concentrations of taletrectinib, which is a substrate of the isoenzyme. Concomitant administration with rifampin, a potent CYP450 3A inducer, decreased taletrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 42% and 86%, respectively. Coadministration with a moderate CYP450 3A inducer is predicted to decrease taletrectinib Cmax and AUC by 40% and 66%, respectively. Reduced therapeutic effectiveness may occur.

MANAGEMENT: Concomitant use of taletrectinib with potent and moderate CYP450 3A inducers should be avoided.

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of taletrectinib. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. In a clinical study, taletrectinib peak plasma concentration (Cmax) increased by 1.8-fold and systemic exposure (AUC) increased by 3.3-fold following concomitant administration of itraconazole, a potent CYP450 3A inhibitor. According to the product labeling, administration of taletrectinib with a moderate CYP450 3A inhibitor is predicted to increase taletrectinib Cmax and AUC by up to 1.5- and 2.6-fold, respectively. Increased exposure to taletrectinib may increase the risk and/or severity of adverse effects such as hepatotoxicity with liver enzyme elevations, lung toxicities, QT prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, and skeletal fractures.

ADJUST DOSING INTERVAL: Coadministration with high-fat food (1000 calories, 50% fat) increased taletrectinib Cmax and AUC by 1.5-fold, and the predicted increase in the QTc interval is 20.5 msec.

MANAGEMENT: The manufacturer recommends avoiding food or drink containing grapefruit during treatment with taletrectinib. In addition, taletrectinib should be administered on an empty stomach at about the same time each day, at least 2 hours before or 2 hours after food intake.