OBJECTIVES: Bedaquiline, a novel anti-tubercular drug with proven bactericidal outcomes has been marketed and a strict post marketing surveillance has be initiated due to reports suggesting concerns regarding the cardiovascular safety. We aimed to systematically ascertain the cardiac safety profile of bedaquiline and evaluate the risk associated with the QTc prolongation.

METHODS: The PubMed database was searched from inception to June 2020 for studies that quote the cardiovascular effects and safety profile of bedaquiline using the keywords 'bedaquiline' or 'bedaquiline safety' or 'cardiac safety' . After removing the duplicates, studies with full text available and published in English language were selected based on quality assessment for data abstraction to evaluate the key findings.

RESULTS: Out of a total of 661 studies reviewed, 31 studies with a total of 1871 drug resistant (MDR/XDR) subjects were evaluated. The dose administered ranged from 25 - 400 mg/day and the length of exposure varied between 7 to 839 days. QTc prolongation of greater than 480 Ms was reported in 108 patients (5.7%) which lead to permanent discontinuation of bedaquiline in 17 patients (17/1871 = 0.9% or 17/108 = 15.7%), while most of the cases were addressed with electrolyte corrections. Bedaquiline was often co-administered with other anti-TB drugs like clofazimine, fluoroquinolones, pretomanid, azithromycin and delamanid which also have a risk of QTc prolongation. So, the QTc prolongation in most of the cases could not only be attributed to bedaquiline. Eight (0.4%) cardiac associated death were reported from different cohorts but neither had they confirmed a QTc prolongation nor a confirmed attribution to bedaquiline.

CONCLUSIONS: Bedaquiline is a tolerable drug with very less incidence of discontinuation (0.9%). The cardiac safety of bedaquiline is challenging and hence, a standardized protocol for ECG monitoring and management of QTc prolongation should be established for monitoring the tuberculosis patients.