Drug Interaction Report

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with inhibitors of the P-glycoprotein (P-gp) efflux transporter may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, respectively. Increased exposure to repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures. However, the interaction has not been studied with P-gp inhibitors that do not also inhibit CYP450 3A4.

MANAGEMENT: Concomitant use of repotrectinib with P-gp inhibitors should generally be avoided. If coadministration is required, caution and clinical monitoring are recommended. Patients should be advised to notify their health care professional if they experience increased side effects of repotrectinib such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and myalgia.

Consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit should be avoided during treatment with repotrectinib as they may increase the blood levels of repotrectinib. This may increase the risk and/or severity of side effects such as dizziness, tiredness, muscle pain, nausea, change in your sense of taste, feeling numbness or tingling in your arms or legs, constipation, trouble with balance, shortness of breath, problems with thinking such as forgetfulness or confusion and hallucinations, as well as more serious side effects such severe or life-threatening inflammation of the lungs and liver injury. Talk to your doctor if you have any questions or concerns. Your doctor may be able to provide alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.