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Drug Interactions between repotrectinib and Torisel

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

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Interactions between your drugs

Moderate

temsirolimus repotrectinib

Applies to: Torisel (temsirolimus) and repotrectinib

GENERALLY AVOID: Coadministration of temsirolimus with inducers of CYP450 3A4 may decrease the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. According to the product labeling, administration of temsirolimus in combination with the potent CYP450 3A4 inducer rifampin, resulted in a 65% and 56% decrease in sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of temsirolimus alone. No significant effect on the pharmacokinetics of temsirolimus was reported. The extent to which other inducers of CYP450 3A4 interact with temsirolimus is unknown.

MANAGEMENT: In the setting of mantle cell lymphoma, concomitant use of temsirolimus with inducers of CYP450 3A4 should generally be avoided. When used for the treatment of renal cell carcinoma, some authorities advise a dose increase from the recommended 25 mg IV once weekly to 50 mg IV once weekly depending on patient tolerability. Based on pharmacokinetic studies, this dosage is predicted to adjust the sirolimus AUC to the range observed without inducers; however, clinical data are lacking. The dosage should be reduced to the normally recommended dose following discontinuation of the potent CYP450 3A4 inducer. Other authorities also advise that temsirolimus should not be used in combination with CYP450 3A4 inducers for longer than 5 to 7 days in these patients.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories
  3. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Major

repotrectinib food

Applies to: repotrectinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. The proposed mechanism 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 repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures.

MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.

References (1)
  1. (2023) "Product Information. Augtyro (repotrectinib)." Bristol-Myers Squibb
Moderate

temsirolimus food

Applies to: Torisel (temsirolimus)

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.

References (1)
  1. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories

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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