Addressing bedaquiline treatment interruptions in the treatment of drug-resistant TB

SETTING: The recommended dosing regimen for bedaquiline (BDQ), consisting of a 2-week loading phase (400 mg/day), followed by a maintenance phase (200 mg three times/week), might pose challenges when treatment is interrupted and needs to be reinitiated. Guidance on BDQ treatment re-initiation is, therefore, needed. OBJECTIVE: This pharmacokinetic-based simulation study aimed to provide recommendations for re-initiating BDQ following treatment interruptions. DESIGN: Simulations of treatment interruptions, defined as any time a patient misses >2 consecutive BDQ doses for up to 56 consecutive days (2 months), were assessed using the BDQ population-pharmacokinetic model. RESULTS: Any treatment interruption lasting <= 28 days prior to completing the 14-day loading phase can be managed by completing the remaining loading doses. Scenarios when it is sufficient to simply restart maintenance dosing are discussed. In some scenarios, treatment interruptions require reloading for I week prior to restarting maintenance dosing. CONCLUSIONS: This simulation study provided recommendations for managing BDQ treatment interruptions and underscores the importance of having a robust population-pharmacokinetic model for TB drugs to inform clinical guidance. Such recommendations are valuable to help ensure optimal treatment with BDQ for treating multidrug-resistant TB.