Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study.

An analysis is presented of the side effects which occurred in 530 patients treated with 6 months chemotherapy for newly detected pulmonary tuberculosis. Five treatment regimens were used. The initial phase of treatment consisted of daily isoniazid, rifampicin and ethambutol (HRE) or isoniazid, rifampicin, streptomycin and pyrazinamide (HRSZ) given for 2 months. The second phase of treatment consisted of isoniazid and rifampicin given twice weekly (H2R2) or isoniazid, rifampicin and ethambutol given daily (4HRE) or intermittently (H1R1E1 or H2R2E2) for 4 months. Side effects were detected in 66 (12.4%) patients. Hepatotoxic reactions occurred in 48 (9%) patients, mainly of amild and transient nature and the majority were attributable to isoniazid. The 'flu like' syndrome occurred in only 2 patients both during the daily phase of treatment, and it was not encountered in patients taking rifampicin intermittently (dose 600 mg). Inclusion of pyrazinamide in the initial phase of 1 regimen did not result in an increase of frequency of side effects. In 56% of patients on pyrazinamide the serum uric acid concentration was elevated but there was no arthralgia. Drug toxicity leading to alteration or withdrawal of treatment occurred in only 10 (1.8%) patients. This study shows that with these 6 month regimens the overall risk of drug toxicity was low, and less than that associated with more conventional treatment regimens.