title: Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis.
abstract: Major adverse reactions to antituberculosis drugs can cause significant morbidity, and compromise treatment regimens for tuberculosis (TB). Among patients treated for active TB we estimated the incidence, and risk factors, of major side effects from first-line anti-TB drugs. Side effects, resulting in modification or discontinuation of therapy, or hospitalization, were attributed on the basis of resolution after withdrawal, and/or recurrence with rechallenge. Among 430 patients treated between 1990 and 1999, the incidence of all major adverse effects was 1.48 per 100 person-months of exposure (95% confidence interval [95% CI], 1.31 to 1.61) for pyrazinamide, compared with 0.49 (95% CI, 0.42 to 0.55) for isoniazid, 0.43 (95% CI, 0.37 to 0.49) for rifampin, and 0.07 (95% CI, 0.04 to 0.10) for ethambutol. Occurrence of any major side effect was associated with female sex (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 4.7), age over 60 years (adjusted hazard ratio, 2.9; 95% CI, 1.3 to 6.3), birthplace in Asia (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 5.0), and human immunodeficiency virus-positive status (adjusted hazard ratio, 3.8; 95% CI, 1.05 to 13.4). Pyrazinamide-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 2.6; 95% CI, 1.01 to 6.6) and birthplace in Asia (adjusted hazard ratio, 3.4; 95% CI, 1.4 to 8.3), whereas rifampin-associated adverse events were associated with age over 60 years (adjusted hazard ratio, 3.9; 95% CI, 1.02 to 14.9) and human immunodeficiency virus-positive status (adjusted hazard ratio, 8.0; 95% CI, 1.5 to 43). The incidence of pyrazinamide-induced hepatotoxicity and rash during treatment for active TB was substantially higher than with the other first-line anti-TB drugs, and higher than previously recognized.
authors.affiliation: Respiratory Epidemiology Unit, Montreal Chest Institute, 1110 Pine Avenue West, Room 103, Montreal, PQ, H3A 1A3 Canada.
authors.forename: Daphne
authors.initials: D
authors.lastname: Yee
authors.forename: Chantal
authors.initials: C
authors.lastname: Valiquette
authors.forename: Marthe
authors.initials: M
authors.lastname: Pelletier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Parisien
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rocher
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D003875:Drug Eruptions / Q000453:epidemiology; D004977:Ethambutol / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006679:HIV Seropositivity; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011718:Pyrazinamide / Q000009:adverse effects / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin