Drug Interactions between cabozantinib and encorafenib

Consumer information for this interaction is not currently available.

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.