Journal Article

Hepatotoxicity of Rifampin-Pyrazinamide and Isoniazid Preventive Therapy and Tuberculosis Treatment

Rob van Hest, Hennie Baars, Sandra Kik, Paul van Gerven, Marie-Christine Trompenaars, Nico Kalisvaart, Sytze Keizer, Martien Borgdorff, Marlies Mensen and Frank Cobelens

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 39, issue 4, pages 488-496
Published in print August 2004 | ISSN: 1058-4838
Published online August 2004 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/422645
Hepatotoxicity of Rifampin-Pyrazinamide and Isoniazid Preventive Therapy and Tuberculosis Treatment

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Background. Severe liver injury has been attributed to preventive treatment of latent tuberculosis infection with a 2-month course of rifampin-pyrazinamide.

Methods. A retrospective cohort study in The Netherlands compared the hepatotoxicity of preventive treatment with rifampin-pyrazinamide with that of preventive treatment with isoniazid, and also with that of treatment for active tuberculosis containing at least isoniazid, rifampin, and pyrazinamide.

Results. Preventive treatment with rifampin-pyrazinamide caused severe hepatotoxicity more often than did preventive treatment with isoniazid (odds ratio [OR], 2.61; 95% confidence interval [CI], 1.26–5.39; P = .012), especially in patients <25 years old. It also caused severe hepatotoxicity more often than triple- or quadruple-drug tuberculosis treatment (OR, 2.61; 95% CI, 1.21–5.59; P = .016), especially if the pyrazinamide dose was ⩾30 mg/kg. Preventive treatment with rifampin-pyrazinamide was more hepatotoxic even when the advised pyrazinamide dose of up to 20 mg/kg for preventive treatment was compared with the pyrazinamide dose of 30 mg/kg for tuberculosis treatment.

Conclusions. Preventive treatment with rifampin-pyrazinamide causes severe hepatotoxicity more often than does preventive treatment with isoniazid or curative treatment for tuberculosis.

Journal Article.  4533 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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