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Drug Interactions between cabozantinib and encorafenib

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

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Interactions between your drugs

Major

cabozantinib encorafenib

Applies to: cabozantinib and encorafenib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of cabozantinib, which is a substrate of the isoenzyme. In healthy subjects, administration of the potent CYP450 3A4 inducer rifampin (600 mg daily for 31 days) decreased single-dose cabozantinib plasma exposure (AUC) by 77%. Reduced therapeutic efficacy of cabozantinib may occur. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Chronic use of potent CYP450 3A4 inducers during treatment with cabozantinib should be avoided whenever possible. If chronic coadministration is required, the daily dosage of cabozantinib should be increased in accordance with the prescribing information for the specific product. For the treatment of progressive, metastatic medullary thyroid cancer (capsule formulation), the recommendation is to increase cabozantinib dosage by 40 mg (e.g., from 140 mg to 180 mg daily or from 100 mg to 140 mg daily) as tolerated, not to exceed 180 mg/day. For the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy (tablet formulation), the recommendation is to increase cabozantinib dosage by 20 mg (e.g., from 60 mg to 80 mg daily or from 40 mg to 60 mg daily) as tolerated, not to exceed 80 mg/day. The original dosage of cabozantinib may be resumed 2 to 3 days after discontinuation of the potent CYP450 3A4 inducer. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath.

References (2)
  1. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis Inc
  2. (2016) "Product Information. Cabometyx (cabozantinib)." Exelixis Inc

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

cabozantinib food

Applies to: cabozantinib

ADJUST DOSING INTERVAL: Food may alter the oral bioavailability of cabozantinib. When healthy subjects were given a single 140 mg oral dose with a high-fat meal, cabozantinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 41% and 57%, respectively, relative to administration under fasting conditions. In clinical studies, patients were administered cabozantinib without food.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of cabozantinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Cabozantinib should be administered at least one hour before or two hours after a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.

References (1)
  1. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis 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:

  • cabozantinib
  • encorafenib

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.

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