Drug Interactions between Coumadin 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.

Nutrition and diet can affect your treatment with warfarin. Therefore, it is important to keep your vitamin supplement and food intake steady throughout treatment. For example, increasing vitamin K levels in the body can promote clotting and reduce the effectiveness of warfarin. While there is no need to avoid products that contain vitamin K, you should maintain a consistent level of consumption of these products. Foods rich in vitamin K include beef liver, broccoli, Brussels sprouts, cabbage, collard greens, endive, kale, lettuce, mustard greens, parsley, soy beans, spinach, Swiss chard, turnip greens, watercress, and other green leafy vegetables. Moderate to high levels of vitamin K are also found in other foods such as asparagus, avocados, dill pickles, green peas, green tea, canola oil, margarine, mayonnaise, olive oil, and soybean oil. However, even foods that do not contain much vitamin K may occasionally affect the action of warfarin. There have been reports of patients who experienced bleeding complications and increased INR or bleeding times after consuming large quantities of cranberry juice, mangos, grapefruit, grapefruit juice, grapefruit seed extract, or pomegranate juice. Again, you do not need to avoid these foods completely, but it may be preferable to limit their consumption, or at least maintain the same level of use while you are receiving warfarin. Talk to a healthcare provider if you are uncertain about what foods or medications you take that may interact with warfarin. It is important to tell your doctor about all medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

When warfarin is given with enteral (tube) feedings, you may interrupt the feeding for one hour before and one hour after the warfarin dose to minimize potential for interaction. Feeding formulas containing soy protein should be avoided.

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Using warfarin together with ethanol can cause you to bleed more easily. If you take warfarin you should avoid large amounts of alcohol, but moderate consumption (one to two drinks per day) are not likely to affect the response to warfarin if you have normal liver function. You may need a dose adjustment in addition to testing of your prothrombin time or International Normalized Ratio (INR). Call your doctor promptly if you have any unusual bleeding or bruising, vomiting, blood in your urine or stools, headache, dizziness, or weakness. 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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Rarely, vitamin supplements containing vitamin K may reduce the effectiveness of warfarin. This may be more likely to occur in individuals who have low levels of vitamin K in their blood. Before using any vitamin supplement, you should check the label to make sure it does not contain vitamin K. If it does, let your doctor know before you start using it. You may need more frequent monitoring of your INR after starting the supplement or whenever it is discontinued, and appropriate adjustments made in your dosage if necessary. It is important to tell your doctor about all other medications you use, including other nutritional supplements and herbs. Do not stop using any medications without first talking to your doctor.

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