Drug Interactions between bedaquiline and rifabutin

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may decrease the plasma concentrations of bedaquiline, which is primarily metabolised by CYP450 3A4 to the major N-monodesmethyl metabolite, M2. Because M2 is 4- to 6-fold less active than the parent drug in terms of antimycobacterial potency, the interaction may diminish the therapeutic effect of bedaquiline. In healthy volunteers, administration of a single 300 mg dose of bedaquiline in combination with rifampin 600 mg once daily for 21 days reduced bedaquiline systemic exposure (AUC) by 52% compared to administration alone. Another study involving healthy volunteers revealed a 20% decrease in the AUC and no change in the Cmax of bedaquiline (400 mg once) when administered with efavirenz (600 mg once daily for 27 days). 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: The concomitant use of bedaquiline with potent or moderate CYP450 3A4 inducers should generally be avoided.