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Drug Interactions between repotrectinib and tamoxifen

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

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Interactions between your drugs

Moderate

tamoxifen repotrectinib

Applies to: tamoxifen and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tamoxifen, which is metabolized by the isoenzyme. In ten healthy subjects, the potent CYP450 3A4 inducer rifampin (600 mg orally once a day for 5 days) decreased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and elimination half-life of tamoxifen (80 mg single oral dose) by 55%, 86% and 44%, respectively, compared to placebo. The AUC of the active N-demethyl metabolite decreased by 62% and Cmax increased by 46%, suggesting enhanced presystemic metabolism in the intestine. Aminoglutethimide has also been reported to significantly increase the clearance of tamoxifen by more than 3-fold. Coadministration of another CYP450 3A4 inducer, bexarotene, resulted in a 35% decrease in plasma concentrations of tamoxifen. The extent to which other CYP450 3A4 inducers may affect tamoxifen is unknown.

MANAGEMENT: In general, agents without CYP450 3A4-inducing activity are preferable in patients treated with tamoxifen, particularly if these agents are to be used for a prolonged period. Otherwise, pharmacologic response to tamoxifen should be monitored closely whenever an inducing agent is added to or withdrawn from therapy, and the tamoxifen dosage adjusted if necessary.

References

  1. Lien EA, Anker G, Lonning PE, et al. "Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide." Cancer Res 50 (1990): 5851-7
  2. Kivisto KT, Villikka K, Nyman L, Anttila M, Neuvonen PJ "Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin." Clin Pharmacol Ther 64 (1998): 648-54
  3. "Product Information. Targretin (bexarotene)." Ligand Pharmaceuticals PROD (2001):
  4. Biochem Pharmacol "Variable contribution of cytochromes P450 2D6, 2C9, and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes." Biochem Pharmacol 53 (1997): 171-8
View all 4 references

Drug and food interactions

Major

repotrectinib food

Applies to: repotrectinib

Consumer information for this interaction is not currently available.

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

tamoxifen food

Applies to: tamoxifen

Talk to your doctor before using tamoxifen with soy products. There is some evidence that substances present in soy may stimulate breast tumor growth and interfere with the action of tamoxifen, 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.

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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.

See also

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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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