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Drug Interactions between cobicistat / elvitegravir / emtricitabine / tenofovir and repotrectinib

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

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Interactions between your drugs

Major

cobicistat repotrectinib

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-glycoprotein (P-gp) in vitro. Drug interaction studies have shown that administration of repotrectinib with itraconazole, a combined 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. 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: Coadministration of repotrectinib with potent or moderate CYP450 3A4 inhibitors should generally be avoided. According to product labeling, moderate and potent CYP450 3A4 inhibitors should be discontinued for 3 to 5 elimination half-lives prior to starting repotrectinib.

References

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

tenofovir cobicistat

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir and cobicistat / elvitegravir / emtricitabine / tenofovir

Using cobicistat together with tenofovir can increase the effects of tenofovir, which can cause new or worse kidney problems. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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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Moderate

emtricitabine cobicistat

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir and cobicistat / elvitegravir / emtricitabine / tenofovir

Cobicistat is a medication used to boost the effects of some medications that treat HIV infection. However, using cobicistat together with other HIV medications, such as emtricitabine, may alter the blood levels and effects of both medications. Using emtricitabine with cobicistat may reduce or increase blood levels of cobicistat. Reduced blood levels of cobicistat may make cobicistat less effective and may cause overall HIV treatment to be less effective. Cobicistat may increase blood levels of emtricitabine which may increase the risk of side effects. Talk to your doctor or pharmacist if you have any questions on how to use these medications properly. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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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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

elvitegravir food

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir

Food significantly increases the absorption of elvitegravir. You should take each dose of elvitegravir with a meal. Taking it on an empty stomach may lead to inadequate blood levels and reduced effectiveness of the medication in treating HIV infection.

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Minor

tenofovir food

Applies to: cobicistat / elvitegravir / emtricitabine / tenofovir

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.