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Drug Interactions between encorafenib and sorafenib

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

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Interactions between your drugs

Major

SORAfenib encorafenib

Applies to: sorafenib and encorafenib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of sorafenib. According to the prescribing information, sorafenib undergoes oxidative metabolism by hepatic CYP450 3A4 as well as glucuronidation by UGT1A9. When a single 400 mg oral dose of sorafenib was administered to healthy volunteers following treatment with the potent CYP450 3A4 inducer rifampin at a dosage of 600 mg once daily for 5 days, mean sorafenib systemic exposure (AUC) decreased by 37% compared to sorafenib administered alone. In another study conducted in 9 patients with advanced hepatocellular carcinoma initiating treatment with sorafenib 400 mg once daily or twice daily, addition of the potent CYP450 3A4 inducer enzalutamide at 160 mg daily starting on day 8 of sorafenib therapy reportedly led to a 60% reduction in mean AUC and 59% reduction in mean peak plasma concentration (Cmax) of sorafenib. The clinical significance of this interaction has not been established, but reduced therapeutic efficacy of sorafenib may occur. In addition, some of the known potent inducers of CYP450 3A4 such as apalutamide, encorafenib, and enzalutamide can cause QT interval prolongation and may have additive effects with sorafenib, resulting in increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Concomitant use of sorafenib with potent CYP450 3A4 inducers should be avoided when possible.

References (4)
  1. (2023) "Product Information. NexAVAR (SORAfenib)." Bayer Pharmaceutical Inc
  2. (2023) "Product Information. Nexavar (sorafenib)." Bayer Plc
  3. (2023) "Product Information. nexAVAR (soRAFENib)." Bayer Australia Limited
  4. Harding JJ, Kelley RK, Tan B, et al. (2020) "Phase Ib study of enzalutamide with or without sorafenib in patients with advanced hepatocellular carcinoma." Oncologist, 25, e1825-36

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

SORAfenib food

Applies to: sorafenib

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.

References (1)
  1. (2005) "Product Information. Nexavar (sorafenib)." Bayer Pharmaceutical Inc

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
  • sorafenib

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