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Drug Interactions between encorafenib and ruxolitinib

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

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Interactions between your drugs

Moderate

ruxolitinib encorafenib

Applies to: ruxolitinib and encorafenib

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ruxolitinib, which is primarily metabolized by the isoenzyme. In healthy subjects, administration of a single 50 mg dose of ruxolitinib following pretreatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for ten days) resulted in a 32% decrease in ruxolitinib peak plasma concentration (Cmax) and a 61% decrease in systemic exposure (AUC) compared to administration of ruxolitinib alone. In addition, the relative exposure to ruxolitinib's active metabolites increased approximately 100%. This increase may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker, pSTAT3 inhibition.

MANAGEMENT: No dosage adjustment is recommended when ruxolitinib is coadministered with a CYP450 3A4 inducer. However, patients should be closely monitored and the dose titrated based on safety and efficacy.

References (1)
  1. (2011) "Product Information. Jakafi (ruxolitinib)." Incyte Corporation

Drug and food interactions

Major

encorafenib food

Applies to: encorafenib

GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of encorafenib, which is primarily metabolized by the isoenzyme. When a single 50 mg dose of encorafenib (equivalent to 0.1 times the recommended dose) was administered with posaconazole, a potent CYP450 3A4 inhibitor, encorafenib peak plasma concentration (Cmax) increased by 68% and systemic exposure (AUC) increased by 3-fold. When the same dose of encorafenib was administered with diltiazem, a moderate CYP450 3A4 inhibitor, encorafenib Cmax increased by 45% and AUC increased by 2-fold. Increased exposure to encorafenib may increase the risk of serious and life-threatening adverse effects such as hemorrhage, uveitis, QT prolongation, hepatotoxicity, dermatologic reactions, and new malignancies.

MANAGEMENT: Concomitant use of encorafenib with grapefruit or grapefruit juice should generally be avoided. If coadministration is required, the manufacturer recommends reducing the encorafenib dose to one-third of the dose used prior to addition of a potent CYP450 3A4 inhibitor or one-half of the dose used prior to addition of a moderate CYP450 3A4 inhibitor. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, the encorafenib dose that was taken prior to initiating the inhibitor may be resumed.

References (1)
  1. (2018) "Product Information. Braftovi (encorafenib)." Array BioPharma Inc.
Moderate

ruxolitinib food

Applies to: ruxolitinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ruxolitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ruxolitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ruxolitinib may be administered with or without food.

References (1)
  1. (2011) "Product Information. Jakafi (ruxolitinib)." Incyte Corporation

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • encorafenib
  • ruxolitinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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.

Medical Disclaimer