Drug Interactions between Iclusig and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice 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. The proposed mechanism 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 repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. 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. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. 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.

MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.

Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with PONATinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of PONATinib. You may be more likely to experience side effects such as nausea; vomiting; abdominal pain; constipation; skin rash; mouth sores; high blood pressure; blood clots; fluid retention; heart failure; liver damage; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems and infections. You should contact your doctor immediately if you develop sudden dizziness, fainting, chest pain, palpitation, shortness of breath, weakness on one side of the body, speech impairment, leg pain or swelling, or any signs of infection, as these may be symptoms of potentially serious side effects associated with PONATinib. You should also seek prompt medical attention if you have signs and symptoms of liver damage such as fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and yellowing of the skin or eyes. 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.

Switch to professional interaction data

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• Iclusig (ponatinib)
• repotrectinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.