Intermittent chemotherapy of pulmonary tuberculosis using rifampicin and isoniazid for primary treatment: the influence of various factors on the frequency of side-effects

Abstract

The incidence of side-effects during treatment with intermittent rifampicin and isoniazid has been related to the isoniazid-inactivation rate and the age and sex of the patients and the dose of rifampicin. The patients were treated with 30 or 15 mg/kg rifampicin plus 15 mg/kg isoniazid once weekly. Of 112 patients, 40 had side-effects. In 39 there were transient febrile reactions (‘flu reactions’); the other patient had thrombocytopenia and purpura. The causal drug was proved to be rifampicin in 33 and considered probable in a further 2. In 6 of these 35 the reactions were also produced by isoniazid; in the remaining 5 the reaction was produced only by isoniazid. Of 42 patients treated with 30 mg/kg rifampicin 45 per cent had side-effects, compared with 23 per cent of 70 treated with 15 mg/kg - a significant difference: Reactions were significantly more frequent in females than males and in older than younger patients. No male patient younger than 36 years had side-effects; but all the female patients over 55 years had side-effects. The increased incidence in females and older patients appears to be associated with the observed increased serum concentrations of rifampicin in these patients.