Additive QTc Prolongation with Concurrent Use of Bedaquiline, Clofazimine, and Fluoroquinolones in MDR-TB: Role of Hypokalemia and Hypomagnesemia as Modifying Risk Factors

Introduction: Oral medications for the treatment of MDR-TB regimens, including bedaquiline, clofazimine, and moxifloxacin, are increasingly prescribed globally. These drugs can lead to increased QTc intervals and ventricular arrhythmias. The risk increases when these medications are combined, as per WHO guidelines. Electrolyte imbalance, common in malnourished MDR-TB patients, can exacerbate this issue. Objective: This narrative review synthesizes available evidence to characterize the additive QTc-prolongation risk of the bedaquiline–clofazimine–moxifloxacin combination and de lineate the specific contributions of electrolyte imbalance as a risk factor. Methods: A narrative review was conducted using databases such as PubMed, Scopus, Embase, and ClinicalTrials.gov. Results: The concurrent use of bedaquiline, clofazimine, and moxifloxacin is associated with additive QTc prolongation of approximately 35–50 ms in many patients, depending on regimen, drug exposure, and patient characteristics. In MDRTB patients, hypokalemia is associated with QTc prolongation, and lower serum potassium levels may increase the risk of clinically significant QT interval prolongation. Hypomagnesemia compounds this risk by driving refractory potassium depletion through impaired Na+/K+-ATPase channel. Together, patients with borderline baseline QTc and untreated electrolyte disturbances may push QTc beyond the critical 500 ms threshold. Conclusion: Correcting the potassium and magnesium levels might become a clinically valuable approach to prevent cardiac events associated with QTc prolongation in patients with MDR-TB along with electrocardiogram monitoring in line with WHO recommendations, is a key component of successful treatment.