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Drug Interactions between flutamide and taletrectinib

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

flutamide taletrectinib

Applies to: flutamide and taletrectinib

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.

Drug and food/lifestyle interactions

Major

taletrectinib food/lifestyle

Applies to: 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.

Moderate

flutamide food/lifestyle

Applies to: flutamide

Consumer information for this interaction is not currently available.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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