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Drug Interactions between Braftovi and Cerdelga

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

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Interactions between your drugs

Major

eliglustat encorafenib

Applies to: Cerdelga (eliglustat) and Braftovi (encorafenib)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of eliglustat, which is primarily metabolized by CYP450 2D6 and, to a lesser extent, CYP450 3A4. Eliglustat is also a substrate of P-gp efflux transporter. In pharmacokinetic studies, treatment with the potent CYP450 3A4/P-gp inducer rifampin (600 mg once daily) decreased eliglustat peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 90% in CYP450 2D6 extensive and intermediate metabolizers administered eliglustat 127 mg twice daily, and 95% in poor metabolizers administered eliglustat 84 mg twice daily.

MANAGEMENT: Concomitant use of eliglustat with potent CYP450 3A4 or P-gp inducers should generally be avoided due to the potential for significantly reduced efficacy.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2014) "Product Information. Cerdelga (eliglustat)." Genzyme Corporation

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Drug and food interactions

Major

eliglustat food

Applies to: Cerdelga (eliglustat)

GENERALLY AVOID: Grapefruit juice may significantly increase the systemic exposure to eliglustat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because eliglustat is predicted to cause prolongation of the PR, QTc, and QRS cardiac intervals at substantially elevated plasma concentrations, consumption of grapefruit juice during treatment may increase the risk of bradycardia, atrioventricular block, cardiac arrest, and serious ventricular arrhythmias such as torsade de pointes.

MANAGEMENT: Patients treated with eliglustat should avoid consumption of grapefruit and grapefruit juice.

References

  1. (2014) "Product Information. Cerdelga (eliglustat)." Genzyme Corporation

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Major

encorafenib food

Applies to: Braftovi (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. (2018) "Product Information. Braftovi (encorafenib)." Array BioPharma Inc.

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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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