Adverse drug reactions associated with first-line anti-tuberculosis drug regimens

BACKGROUND: Standard treatment of active tuberculosis (TB) consists of Isoniazid (INH), rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Although this regimen is effective in treating active TB, it is associated with many adverse drug reactions (ADRs) and poses a significant challenge to completion of treatment. OBJECTIVES: To examine the incidence of major ADRs and risk factors associated with first-line anti-tuberculosis medications. METHODS: This study evaluated patients receiving treatment for active TB from a population-based database (2000-2005). The nature of the ADRs, likelihood of association with the study medications and severity were evaluated. RESULTS: A total of 1061 patients received treatment, of whom 318 (30%) had at least one major ADR. The overall incidence of all major ADRs was 7.3 events per 100 person-months (95%CI 7.2-7.5): 23.3 (95%CI 23.0-23.7) when on all four first-line drugs, 13.6 (95%CI 13.3-14.0) when on RMP, INH and PZA, and 2.4 (95%CI 2.3-2.6) when on INH and RMP. Adjusted hazard ratio (HR) revealed that combination regimens containing PZA, females, subjects aged 35-59 and >= 60 years, baseline aspartate aminotransferase >= 80 U/1 and drug resistance were associated with any major event. CONCLUSIONS: First-line anti-tuberculosis drugs are associated with significant ADRs. There are several risk factors associated with the development of ADRs, including exposure to regimens containing PZA.