Common Adverse Reactions and Management Strategies of First-Line Anti-Tuberculosis Drugs

Kun He,* Jing Zhang,* Xiang Du, Xiaoqing He, Yanming Zeng, Min Liu Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Liu, Email gwzxliumin@foxmail.comAbstract: This review synthesizes evidence from recent clinical and mechanistic studies published between 2015 and 2024 to provide updated insights into the prevention and management of adverse drug reactions (ADRs) associated with first-line anti-tuberculosis drugs (ATDs)—namely isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB)—which are essential for tuberculosis (TB) treatment but frequently cause significant ADRs that threaten therapeutic success. We examine four major toxicities: hepatotoxicity (primarily from INH and RIF, mediated by oxidative stress, mitochondrial dysfunction, and cytochrome P450 induction); peripheral neuropathy (driven by INH-induced pyridoxine depletion and EMB-related copper chelation leading to optic and axonal damage); central nervous system (CNS) toxicity (notably INH-induced seizures due to GABAergic disruption); and myelosuppression (mainly RIF- or PZA-related, involving oxidative injury to hematopoietic stem cells and impaired DNA synthesis). Key risk factors include advanced age, malnutrition, pre-existing organ dysfunction, and pharmacogenetic variations (eg, NAT2 acetylator status). Management strategies emphasize protocol-driven monitoring—including baseline and serial liver function tests (LFTs), complete blood counts (CBC), neurologic exams, and monthly visual assessments for EMB—and graded interventions based on severity thresholds (eg, temporary discontinuation if ALT > 3× upper limit of normal (ULN) with symptoms or > 5× ULN asymptomatic), alongside targeted therapies such as pyridoxine for neuropathy and N-acetylcysteine for hepatotoxicity. Proactive measures, including pretreatment risk stratification, patient education, and multidisciplinary coordination, are critical to optimizing adherence and outcomes. Effective management of first-line anti-TB drug toxicity requires mechanism-informed monitoring, individualized interventions, and proactive patient education to maintain treatment adherence and improve global TB outcomes.Keywords: anti-tuberculosis drugs, adverse reactions, hepatotoxicity, neurotoxicity