Drug Interactions between repotrectinib and Tenex

Avoid consuming grapefruit or grapefruit juice during treatment with guanFACINE, as it may increase blood levels and effects of the medication. This may cause blood pressure to fall excessively, especially when you rise from a sitting or lying position. The risk of other side effects such as drowsiness, dizziness, lightheadedness, fainting, headache, palpitations, and heart rate changes may also increase. Additionally, you should avoid or limit the use of alcohol while being treated with guanFACINE. Combining the medication with alcohol can intensify sedative and blood pressure lowering effects, which may increase the risk of falls and injury. 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. If you are using a long-acting or extended-release formulation of the medication, make sure you do not take it with a high-fat meal. Doing so results in increased absorption and elevated blood levels of the medication. Talk to your doctor or pharmacist if you have any questions or concerns.

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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.