Drug candidate, hepatotoxic potential

Are Reactive Metabolite Trapping and Covalent Binding Studies Reliable Predictors of Hepatotoxic Potential of Drug Candidates ... 

Aside from consideration of drug toxicity, some antimicrobial use requires more in tensive risk-benefit analysis. An example of this is the decision to use isoniazid prophylactically to prevent tuberculosis. Because the hepatotoxicity of isoniazid increases in frequency with age, older persons (>45 years) who are candidates for isoniazid prophylaxis (positive skin test) must have additional risk factors for tuberculosis to balance the potential toxic effects. These include evidence of recent skin-test conversion, immunosuppression, or previous gastrectomy. Older patients without additional risk factors are more likely to suffer toxicity from isoniazid than derive benefit from its use. ... 

Tuberculosis chemoprophylaxis has been retrospectively evaluated in 63 Spanish patients with latent tuberculosis out of 497 with inflammatory bowel disease who were candidates for anti-TNFa therapy [31 ]. Skin tests for tuberculosis were positive in 86% after a single exposure, but 14% needed a booster. There were no susceptibility factors for hepatotoxicity. All but one was treated with isoniazid alone for 6 or 9 months, and only one required chemoprophylaxis withdrawal because of hepatotoxicity. There were no cases of active tuberculosis in the patients who were treated with anti-TNFa therapy. The authors concluded that chemoprophylaxis is safe in patients with inflammatory bowel disease, even in those taking concomitant, potentially hepatotoxic drugs. 

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