title: Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide.
abstract: Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D007565:Jaundice / Q000139:chemically induced; D008099:Liver / Q000187:drug effects; D011718:Pyrazinamide / Q000009:adverse effects / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*; D014390:Tuberculosis, Meningeal / Q000188:drug therapy; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy; D014399:Tuberculosis, Spinal / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin