Hepatotoxicity of antitubercular treatments. Rationale for monitoring liver status

Drug Safety : an International Journal of Medical Toxicology and Drug Experience
F DurandJ Bernuau

Abstract

The standard antitubercular regimen currently includes a combination of 3 antitubercular agents: isoniazid, rifampicin (rifampin) and pyrazinamide. Administration of a fourth agent, ethambutol, is recommended when isoniazid resistance is suspected. Two of these 4 agents (isoniazid and pyrazinamide) are major hepatotoxins. The remaining 2 agents (rifampicin and ethambutol) are rarely or not hepatotoxic. However, rifampicin, which is a powerful enzyme inducer, may enhance the hepatotoxicity of isoniazid. In patients receiving a combination of isoniazid, rifampicin and pyrazinamide, 2 patterns of fulminant liver injury can be observed. The first pattern is characterised by an increase in serum transaminase activity that occurs soon (usually within the first 15 days) after initiation of treatment. This pattern is likely to be caused by rifampicin-induced isoniazid hepatotoxicity. The prognosis is good in most cases. The second pattern is characterised by an increase in serum transaminase activity that occurs late (usually more than 1 month) after the initiation of treatment. It has been suggested that this pattern may be related to pyrazinamide hepatotoxicity. The prognosis of this type of hepatitis is generally poor. In order to r...Continue Reading

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