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Drug Interactions between Plan B One-Step and repotrectinib

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

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Interactions between your drugs

Major

levonorgestrel repotrectinib

Applies to: Plan B One-Step (levonorgestrel) and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with repotrectinib may decrease the plasma concentrations of hormonal contraceptives and possibly render them ineffective. The proposed mechanism is repotrectinib-mediated induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of hormonal contraceptives. Although studies have not been conducted with hormonal contraceptives, when midazolam, a sensitive CYP450 3A4 substrate, was administered to subjects who were previously administered repotrectinib (160 once daily for 14 days followed by 160 mg twice daily for 7 days), the systemic exposure (AUC) and peak plasma concentration (Cmax) of midazolam decreased by 69% and 48%, respectively. In addition, repotrectinib can cause fetal harm when administered to a pregnant woman.

MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable during concomitant therapy with repotrectinib. Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy when receiving repotrectinib. Because use of repotrectinib may cause embryo-fetal harm, it is particularly important that patients not become pregnant during treatment. Therefore, hormonal contraceptives should not be used as method of birth control in women of childbearing potential treated with repotrectinib. Female patients of reproductive potential should use a highly effective, non-hormonal method of contraception during treatment and for 2 months after treatment. Male patients with female partners of reproductive potential should use effective contraception during treatment with repotrectinib and for 4 months after treatment.

References

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

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

levonorgestrel food

Applies to: Plan B One-Step (levonorgestrel)

Grapefruit juice may increase the blood levels of certain medications such as levonorgestrel. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with levonorgestrel. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

Switch to professional interaction data

Minor

levonorgestrel food

Applies to: Plan B One-Step (levonorgestrel)

Information for this minor interaction is available on the professional version.

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.