Drug Interactions between taletrectinib and verapamil

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.

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.

Ask your doctor before using verapamil together with ethanol (alcohol). Verapamil may increase the blood levels and intoxicating effects of ethanol (alcohol). 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.

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.