Adverse Drug Reactions in Long-Duration Anti-Tubercular Therapy: Risk Factors, Clinical Manifestations, and Management

Tuberculosis continues to pose a significant global health burden, often requiring prolonged anti- tubercular therapy (ATT) in conditions such as extrapulmonary, central nervous system, skeletal, and multidrug-resistant tuberculosis. While standard short-course regimens are generally well tolerated, extended treatment durations lead to increased cumulative drug exposure and a higher likelihood of adverse drug reactions (ADRs). These reactions can range from relatively mild effects, such as gastrointestinal discomfort, to serious complications including hepatotoxicity, optic neuritis, ototoxicity, and neuropsychiatric disturbances. Importantly, ADRs are a major contributor to treatment interruption, poor adherence, and ultimately therapeutic failure, which may facilitate the development of drug resistance. This review aims to provide a comprehensive overview of the epidemiology, underlying mechanisms, risk factors, and clinical manifestations of ADRs associated with long-duration ATT. It also emphasizes the importance of early detection, regular monitoring, and preventive strategies to improve patient safety and treatment outcomes.