Drug Interactions between st. john's wort and taletrectinib

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.

While you are taking St. John's wort, you must not eat or drink certain foods and beverages that are high in tyramine. Eating these foods while you are taking St. John's wort can raise your blood pressure to dangerous levels. This may cause life threatening symptoms such as sudden and severe headache, confusion, blurred vision, problems with speech or balance, nausea, vomiting, chest pain, seizure (convulsions), and sudden numbness or weakness (especially on one side of the body). Call your doctor at once if you have any of these symptoms. Foods that are high in tyramine include: air dried meats, aged or fermented meats, sausage or salami, pickled herring, and any spoiled or improperly stored beef, poultry, fish, or liver, red wine, beer from a tap, beer that has not been pasteurize, aged cheeses, including blue, brick, brie, cheddar, parmesan, romano, and swiss, sauerkraut, over the counter supplements or cough and cold medicines that contain tyramine, soy beans, soy sauce, tofu, miso soup, bean curd, fava beans, or yeast extracts (such as Marmite). Caffeine intake should be limited as well. You should avoid or limit the use of alcohol while being treated with St. John's wort. Alcohol can increase the nervous system side effects of St. John's wort such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Talk to your doctor or pharmacist if you have any questions or concerns.