Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations

Tuberculosis (TB) remains a critical global public health challenge, requiring therapeutic strategies that ensure high cure rates while minimizing bacillary transmission. The 2022 World Health Organization (WHO) update for drug-resistant TB treatment prioritized a novel, 6-month, all-oral regimen composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) as the preferred treatment for rifampicin- and multidrug-resistant tuberculosis (RR-/MDR-TB). However, the clinical success of this shortened therapy is intrinsically linked to managing complex drug–drug interactions and treatment-emergent adverse effects which may necessitate regimen modifications. This article provides a comprehensive pharmacological review of the BPaLM components, detailing their mechanisms of action, pharmacokinetics (absorption, metabolism, and excretion), and safety profiles. Furthermore, we analyze critical drug interactions—including those involving food and antacids—and provide evidence-based guidance for special clinical populations, such as pregnant and breastfeeding women, and patients with hepatic or renal impairment. Mastery of these pharmacological nuances is essential for clinicians to optimize treatment adherence and ensure improved treatment completion rates and reduced resistance emergence.