A comparison of the toxicity of prothionamide and ethionamide: A report from the research committee of the british tuberculosis association

Abstract

The present study was planned to assess the tolerance of patients for and liver toxicity of 0·75 g. prothionamide daily compared with 0·75 g. ethionamide in the treatment of pulmonary tuberculosis. The patients were also treated with 300 mg. isoniazid and 0·75 g. or 1 g. streptomycin daily. The trial was of ‘double blind’ design. The drug regimen was allocated to each patient at random. The duration of treatment was 10 weeks. Tolerance was assessed by weekly recordings of relevant symptoms and signs and liver toxicity by fortnightly estimations of serum bilirubin and transaminase. Fifty-three patients received prothionamide and 48 ethionamide. Anorexia, nausea or vomiting were reported in 17 (32%) patients treated with prothionamide and in 24 (50%) patients treated with ethionamide. This difference is not significant (P > 0·10). In 14 (26%) patients in the prothionamide group and in 15 (31%) patients in the ethionamide group these symptoms were graded as slight, and in 3 (6%) patients treated with prothionamide and in 9 (19%) patients treated with ethionamide they were classified as severe. These differences are not significant (0·10 > P > 0 ·05). Two (4%) patients in the prothionamide group were withdrawn from treatment because of severe gastro-intestinal intolerance. Elevation of serum transaminase was more commonly detected than a rise in serum bilirubin. Five (9%) patients in the prothionamide group and 5 (10%) patients in the ethionamide group had elevated transaminase or serum bilirubin levels in two consecutive estimations. Abnormal liver function tests in two consecutive estimations occurred more often in patients with a pre-treatment weight of less than 64 kg. (140 lbs.). The average weight gain in patients treated with prothionamide was significantly greater than in patients treated with ethionamide. The results suggest that prothionamide may be better tolerated than ethionamide, though the difference, if it exists, is not great. It is equally liable to cause disturbance of liver function. Regular liver function tests are advised for all patients treated with these drugs.