Adverse drug reactions of first-line antitubercular drugs: A retrospective study on characteristics, management, factors, and impacts

Abstract

Objective: To elucidate the characteristics, management strategies, risk factors, and clinical impacts associated with adverse drug reactions (ADRs) induced by first-line antitubercular drugs to enhance tuberculosis (TB) management. Methods: A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak, Malaysia. Only the initial TB treatment and occurrence of specific ADRs within the study period were considered. Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs. Results: Among 2 953 cases, 705 (23.9%) developed ADRs. Cutaneous reactions were the most prevalent (47.1%), followed by hepatotoxicity (32.8%) and gastrointestinal disturbances (29.8%). Six out of seven types of ADRs investigated occurred within the intensive phase, mostly manifesting at approximately 2 weeks of initiation. Hepatotoxicity resulted in the majority (85.3%) of treatment discontinuations, while vision problems led to treatment modifications in half of the cases. Risk factors for all ADRs included age ≥60 years, females, illicit drug use, and comorbidities such as HIV-positive, diabetes, and chronic liver disease. Alcohol consumption was independently associated with hepatotoxicity. ADRs caused around one-third of interruptions exceeding 2 weeks (33.0%) and subsequently necessitated treatment restarts (34.5%). Conclusions: Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment. Close ADR monitoring and reporting are essential to strengthen ADR management.

Keywords

• adverse events
• cutaneous reactions
• hepatotoxicity
• gastrointestinal disturbances
• risk factors
• tuberculosis