Incidence and risk factors of major toxicity associated to first-line antituberculosis drugs for latent and active tuberculosis during a period of 10 years.

INTRODUCTION Adverse drug reactions (ADR) to first-line antituberculosis drugs are frequent and have important implications that may affect the effectiveness of treatment and course of tuberculosis (TB). MATERIAL AND METHODS Retrospective data analysis of clinical records and national registration forms from patients with ADR to first line antituberculosis that occurred between 2004 and 2013 at a Portuguese Pulmonology Diagnostic Centre, and from a case-control population matched by sex, age and year of initiation of treatment. RESULTS Of the 764 patients treated with antituberculosis drugs, 55 (52.7% male, 92.7% European, mean age 50.8±19.5 years) had at least one severe ADR and six had a second ADR, for a total of 61 events. The most frequent ADR were hepatotoxicity (86.9%), rash (8.2%) and others, such as ocular toxicity, gastrointestinal intolerance and angioedema (4.9%). Isoniazid, alone or in combination, was the antituberculosis drug most associated to toxicity. Due to ADR, treatment time changed an average of 1.0±2.6 months (range -3.4 to 10.6). There was no correlation between age or gender and the overall incidence of ADR although we found a significant association between younger age and an increased risk of hepatotoxicity (P=0.035). There was also a statistically significant relationship between ADR and diabetes mellitus (P=0.042) but not for other comorbidities or multi-resistant TB risk factors. CONCLUSIONS This study found a high frequency of ADR with strong impact on subsequent therapeutic orientation. What seems to be of particular interest is the relationship between ADR and diabetes mellitus and the increased frequency of hepatotoxicity in younger patients.