Drug Interactions between rifabutin and vemurafenib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of vemurafenib, which has been shown in vitro to be a substrate of the isoenzyme. According to the product labeling, administration of a single 960 mg dose of vemurafenib with the potent CYP450 3A4 inducer rifampin at a dosage of 600 mg once daily resulted in a 40% decrease in vemurafenib systemic exposure (AUC) relative to vemurafenib administered alone, with no effect on peak plasma concentration (Cmax). Reduced therapeutic efficacy of vemurafenib 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: Concomitant use of vemurafenib with potent CYP450 3A4 inducers should generally be avoided. Alternative therapeutic agents with less enzyme induction potential should be considered whenever possible during treatment with vemurafenib. If coadministration is required, the manufacturer recommends increasing the dose of vemurafenib by 240 mg (one tablet) as tolerated. Close monitoring for toxicities (e.g., QT prolongation, hepatotoxicity, nephrotoxicity, photosensitivity, dermatologic reactions, uveitis) is advised following dose increase. Two weeks after discontinuation of the strong CYP450 3A4 inducer, the vemurafenib dose that was taken prior to initiating the inducer may be resumed.