Drug Interactions between methotrexate 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.

Caffeine may reduce the effectiveness of methotrexate in the treatment of arthritis. If you are receiving methotrexate for arthritis, you may want to limit your intake of caffeine-containing foods and medications. Check with your doctor or pharmacist if you have concerns or are uncertain what products may contain caffeine.

Methotrexate may cause liver problems, and using it with other medications that can also affect the liver such as ethanol (alcohol) may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your doctor or pharmacist if you have any questions or concerns. 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.

Caffeine may reduce the effectiveness of methotrexate in the treatment of arthritis. If you are receiving methotrexate for arthritis, you may want to limit your intake of caffeine-containing foods and products. Contact your doctor if your symptoms worsen or your condition changes during treatment with these medications. Your doctor may be able to prescribe alternatives that do not interact. 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.