Drug Interactions between Diltzac 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.

Alcohol can lower your blood pressure and add to the effects of dilTIAZem. You may experience dizziness, lightheadedness, fainting, or a rapid heartbeat if you drink alcohol with dilTIAZem, especially when you first start taking the medication or just after a dose increase. Grapefruit juice may also increase the effects of dilTIAZem in some people by increasing its levels in the blood. You may want to limit alcohol intake and avoid excessive consumption of grapefruit and grapefruit juice during treatment with dilTIAZem. However, if you have been regularly consuming grapefruit or grapefruit juice with dilTIAZem, do not alter the amounts of these products in your diet without first talking to your doctor or other healthcare professional. Contact your doctor if your condition changes or you experience increased side effects of dilTIAZem such as headache, irregular heartbeat, swelling, unexplained weight gain, or chest pain. Orange juice is not expected to interact.

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Using dilTIAZem together with multivitamin with minerals can decrease the effects of dilTIAZem. Talk with your doctor before using dilTIAZem 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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