Drug Interactions between Calan 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.

You may take verapamil with or without food, but take it the same way every time. You should avoid consuming grapefruit or grapefruit juice as much as possible during treatment with verapamil. If you have been regularly consuming grapefruit or grapefruit juice with verapamil, do not increase or decrease the amounts of these products in your diet without first talking to your doctor. Grapefruit juice can increase the blood levels and effects of verapamil. Contact your doctor if you experience sudden, unexplained weight gain; swelling of the hands, ankles, or feet; chest pain; or difficulty breathing. Avoid driving or operating hazardous machinery until you know how the medication affects you, and use caution when getting up from a sitting or lying position. 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.

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Ask your doctor before using verapamil together with ethanol. Verapamil may increase the blood levels and intoxicating effects of ethanol. This can cause symptoms of extreme drowsiness, confusion, and nausea. If you experience any of these side effect you should avoid activities requiring mental alertness. 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.

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Using verapamil together with multivitamin with minerals can decrease the effects of verapamil. Talk with your doctor before using verapamil and multivitamin with minerals together. You may need a dose adjustment or need your blood pressure checked more often if you take both medications. 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.

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