Toxicity from rifampicin plus isoniazid and rifampicin plus ethambutol therapy

Abstract

One hundred and five patients with pulmonary tuberculosis diagnosed for the first time were treated with a combination of rifampicin 600 mg daily plus isoniazid 300 mg daily.Treatment was discontinued in 3 patients because of a violent hypersensitivity reaction: in 2 of these patients there were raised serum bilirubin and transaminase levels and in the other raised transaminase levels.Of the 105 patients some disturbance of liver function was noticed in 37 (35 per cent). Of these 37 patients 23 (22 per cent) had transient elevation of transaminase levels and 14 (13 per cent) had elevation of serum bilirubin and transaminase levels. Apart from 2 patients who, in addition, had a hypersensitivity reaction, disturbance of liver function was associated with little or no constitutional disturbance. Of 12 patients with elevated serum bilirubin not associated with a hypersensitivity reaction treatment was continued in 4; was stopped in 4 but later successfully reinstituted; was stopped in 2 and finally abandoned after drug rechallenge; and in 2 patients treatment was abandoned without re-challenge though in 1 of these treatment was successfully restarted after 5 months.A transient skin rash was noted in 8 (7·6 per cent) patients.72 patients with previously treated pulmonary tuberculosis were retreated with a combination of rifampicin 600 mg daily plus ethambutol 25 mg per kilo body-weight daily reducing to 15 mg after two months. No generalised hypersensitivity reactions were noted. Of the 72 patients some disturbance of liver function was noted in 7 (10 per cent). Of these 7 patients, 6 had transient elevations of transaminases and 1 had elevation of serum bilirubin and transaminase levels which returned to normal with continuation of treatment.Two patients (3 per cent) developed a skin rash and treatment was discontinued for this reason in 1. One patient had optic neuritis: but since stopping ethambutol initial visual acuity has been regained though colour vision is still defective.Disturbance of liver function was notably more frequent with rifampicin plus isoniazid than with rifampicin plus ethambutol, but was usually transient and always easily manageable.