Drug Interactions between fexinidazole 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.

Food can enhance the levels of fexinidazole in your body. To ensure maximal oral absorption, fexinidazole should be administered with or immediately after the main meal of the day. This will make it easier for your body to absorb the medication. Use of herbal medicines and supplements during treatment with fexinidazole should be avoided. Grapefruit or grapefruit juice should not be consumed during treatment with fexinidazole. Grapefruit juice can significantly increase the blood levels and effects of fexinidazole, which can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a rare side effect. You may be more susceptible if you have a heart condition called congenital long QT syndrome, other cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting). You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone. Consumption of alcoholic beverages or products containing alcohol or propylene glycol during treatment with fexinidazole may occasionally trigger a reaction in some patients similar to the disulfiram reaction, which includes unpleasant effects such as flushing, throbbing in head and neck, throbbing headache, difficulty breathing, nausea, vomiting, sweating, thirst, chest pain, rapid heartbeat, palpitation, low blood pressure, dizziness, lightheadedness, blurred vision, and confusion. Rarely, more severe reactions may include abnormal heart rhythm, heart attack, heart failure, unconsciousness, convulsions, and even death. Patients treated with fexinidazole should avoid using any products containing alcohol or propylene glycol during and for at least 48 hours after completion of therapy. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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.