Bedaquiline is a diarylquinoline approved for drug-resistant TB. Its novel mechanism targets which mycobacterial component, and what is the key black-box warning that mandates ECG monitoring?
- A Inhibits mycobacterial cell wall synthesis; black-box warning is peripheral neuropathy
- B Inhibits mycobacterial ATP synthase (F0F1-ATPase subunit c); black-box warning is QT prolongation and arrhythmia ✓
- C Inhibits mycobacterial RNA polymerase; black-box warning is hepatotoxicity
- D Inhibits mycobacterial DNA gyrase; black-box warning is tendon rupture
Explanation
Bedaquiline is a first-in-class inhibitor of the mycobacterial ATP synthase (specifically the F0 oligomeric c-ring subunit), disrupting mycobacterial energy production in a manner highly selective for mycobacteria over mammalian cells. This mechanism is entirely novel and not shared by any other anti-TB drug. Its black-box warning is QT prolongation (due to hERG channel effects) with potential for fatal arrhythmia, necessitating ECG monitoring at baseline, 2 weeks, and monthly during therapy. An increased risk of unexplained deaths was noted in clinical trials, making close monitoring mandatory. Hepatotoxicity is a warning for rifampicin and pyrazinamide.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.