Hepatotoxicity of the combination of rifampin-ethionamide in the treatment of multibacillary leprosy.
During treatment of multibacillary leprosy with the combination rifampin (RMP) 600 mg, ethionamide (ETH) 500 mg, and either dapsone (DDS) or clofazimine (CLO) 100 mg, hepatotoxicity was observed in 4.5% of 596 patients. Hepatitis appeared after 5-186 days, with a mean of 93 days and a median of 76 days. Mortality was 26%. ETH and DDS or CLO were administered daily in all regimens in which hepatitis occurred. RMP was given either daily or daily during the first two weeks or eight weeks, followed by a once-weekly dose. It is concluded that the combination RMP + ETH is the toxic component. In some patient groups there was a high correlation of toxicity with age. A regimen in which RMP was administered only twice a week during three months was not accompanied by hepatotoxicity. Future studies should show if reduction of the daily dose of ETH or reduction of the duration of the administration of RMP + ETH might reduce the incidence of hepatotoxicity while conserving the efficacy.
D000293:Adolescent; D000328:Adult; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002648:Child; D002986:Clinical Trials as Topic; D002991:Clofazimine / Q000009:adverse effects; D003622:Dapsone / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005000:Ethionamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007918:Leprosy / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects
D003622:Dapsone; D002991:Clofazimine; D005000:Ethionamide; D012293:Rifampin