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Drug Interactions between taletrectinib and toremifene

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

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Interactions between your drugs

Major

toremifene taletrectinib

Applies to: toremifene and taletrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Toremifene has the potential to prolong the QT interval of the electrocardiogram in some patients. 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. The effect on the QT interval is dose- and concentration-dependent. In a placebo-controlled, parallel-design clinical trial, the mean QTc interval prolongation was 21 to 26 ms with 80 mg toremifene, and the 20 mg dose also affected the QTc interval. Abnormal new U waves were observed in 4.3% of subjects with the 80 mg dose. There are no data available for the therapeutic 60 mg dose. 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, women and elderly patients may be more susceptible to the QT prolonging effects of drugs.

MANAGEMENT: Coadministration of toremifene with other drugs that can prolong the QT interval should generally be avoided. If treatment with other QT-prolonging drugs is required, interruption of toremifene therapy should be considered. Caution and clinical monitoring are recommended if concomitant use is unavoidable. In patients at increased risk, electrocardiograms (ECGs) are recommended at baseline and as clinically indicated. 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

toremifene food/lifestyle

Applies to: toremifene

You should avoid drinking grapefruit juice during treatment with toremifene. Grapefruit juice may increase the blood levels of toremifene. This can make you more likely to develop side effects such as vaginal bleeding, blood clots, or an irregular heart rhythm that may be serious or life-threatening. Contact your doctor if you experience potential signs and symptoms of blood clots such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling your arms or legs. You should also seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, or fast or pounding heartbeats during treatment with toremifene.

Talk to your doctor before using toremifene with soy products. There is some evidence that substances present in soy may stimulate breast tumor growth and interfere with the action of toremifene, although this has not been proven. Whether soy products are effective for hot flashes is also uncertain. 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.

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.