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Drug Interactions between entrectinib and Protropin

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

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Interactions between your drugs

Moderate

somatrem entrectinib

Applies to: Protropin (somatrem) and entrectinib

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of entrectinib, which is a substrate of the isoenzyme. When a single 600 mg dose of entrectinib was administered with rifampin, a potent CYP450 3A4 inducer, entrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 56% and 77%, respectively. Coadministration of entrectinib with a moderate CYP450 3A4 inducer is predicted to decrease entrectinib Cmax and AUC by 43% and 56%, respectively. Reduced therapeutic efficacy may occur. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of entrectinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References

  1. (2019) "Product Information. Rozlytrek (entrectinib)." Genentech

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Drug and food interactions

Major

entrectinib food

Applies to: entrectinib

GENERALLY AVOID: Grapefruit juice and Seville oranges may increase the plasma concentrations of entrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but pharmacokinetic data are available for the potent CYP450 3A4 inhibitor, itraconazole. When a single 100 mg dose of entrectinib was administered with itraconazole, entrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.7- and 6-fold, respectively. Coadministration of entrectinib with a moderate CYP450 3A4 inhibitor is predicted to increase entrectinib Cmax and AUC by 2.9- and 3-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 entrectinib may increase the risk and/or severity of adverse effects such as cognitive impairment, mood disorders, dizziness, sleep disturbances, liver enzyme elevations, hyperuricemia, congestive heart failure, edema, myocarditis, QT prolongation, vision problems, anemia, and neutropenia.

MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, and Seville oranges during treatment with entrectinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2019) "Product Information. Rozlytrek (entrectinib)." Genentech

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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.


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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.