Drug Interaction Report

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Taletrectinib may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a safety population study, of the 351 patients who received taletrectinib, 13% experienced an increase in QTcF of greater than 60 msec compared to baseline and 2.6% had an increase in QTcF to greater than 500 msec. Overall, 3.4% of patients had Grade 3 or higher QTc interval prolongation. The median time from the first dose of taletrectinib to the onset of ECG QT prolongation was 22 days (range: 1 day to 38.7 months). QTc prolongation led to dose interruption and dose reduction, each in 2.8% of patients treated with taletrectinib. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of taletrectinib with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Patients should have electrocardiograms (ECGs) performed prior to initiation of taletrectinib and periodically during treatment as appropriate based on individual risk factors. Adjust the frequency of monitoring based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications associated with QTc interval prolongation. Because hypokalemia and hypomagnesemia are risk factors for ventricular arrhythmias, electrolyte levels should also be obtained prior to and during treatment, and any abnormalities corrected as necessary. Significant prolongation of the QTc interval may occur when taletrectinib is taken with food. Patients should be advised to administer/ take taletrectinib on an empty stomach. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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.

Grapefruit juice may increase the blood levels of etrasimod. You should avoid grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with etrasimod unless directed otherwise by your doctor. Talk to your doctor if you have any questions or concerns. Contact your doctor if your condition changes or you experience increased side effects, such as fever, high temperature or flu-like symptoms, severe headache, confusion, seizures, dizziness, tiredness, lightheadedness, chest pain, shortness of breath, or irregular or abnormal heartbeat, blurriness or shadows in the center of your vision, and nausea, vomiting, abdominal pain, anorexia, or jaundice and/or dark urine. 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.