Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis

The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. Final termination of either isoniazid, rifampin or pyrazinamide because of severe side-effects was necessary in 121 of the 519 patients (23%). The most severe side-effects leading to final termination of one drug were hepatotoxicity (11%), exanthema (6%), and arthralgia (2%). Pyrazinamide showed more severe side-effects (15%) than isoniazid (7%) and rifampin (1.5%), Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4;95% confidence interval (95% CI) 1.6-7.6; p=0.0026) and an age greater than or equal to 60 yrs (OR 1.9; 95% CI 1.2-3.2; p=0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p=0.0045; age greater than or equal to 60 yrs: OR 2.1, 95% CI 1.3-3.5; p=0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged greater than or equal to 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.