The risk of toxicity, particularly hepatotoxicity from INH, increases with age.25,33–37 However, a large RCT has not found a similar pattern with 4 R.25,71 It is unclear whether there is an increase in adverse events in older patients taking 3HP. Of note, a Chinese trial of 3HP vs a twice-weekly two-month regiment of INH and rifapentine in patients aged 50-69 was stopped early due to a high rate of adverse events in both study arms (1.1% rate of severe adverse events in the 3HP arm).72 Furthermore, a large Taiwanese study of older patients with poorly controlled diabetes revealed a similar rate of severe adverse events in 3HP vs 9H but a higher rate of mild adverse events with 3HP.73 However, a large American observational study suggested a lower rate of adverse events with 3HP vs 4 R in patients over 50 years,74
Good practice statements
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A carefully weighing of individual risks and benefits when considering TB preventive treatment in older patients, should be undertaken, considering the potential toxicity of treatment as well as both the risk of reactivation and the risk of a poor outcome if active TB develops; age alone should not be the determining factor in declining to offer tuberculosis preventive treatment.
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In older patients, 4 months of daily rifampin or once-weekly rifapentine and isoniazid for 3 months remain the preferred TB preventive treatment regimens.
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