Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study

Abstract

Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection

“…A total of 23 publications related to RCTs and 55 related to nonrandomized studies were included. A flow diagram documenting the process of study selection is provided in Figure .…”

Does tuberculosis threaten our ageing populations?

“…Hepatotoxicity is a common adverse effect as a result of treatment with isoniazid, rifampicin and pyrazinamide, ranging from mild reversible abnormalities of transaminases to fulminant liver failure, and hepatotoxicity from anti-tuberculous drugs rises significantly with increasing age [ 38 , 55 , 56 ]. TB drug related hepatotoxicity in those older than 65 years incurs an odds ratio of 1.71 (CI 95 % 1.24–2.35) [ 56 ], although cessation of isoniazid therapy due to suspected hepatotoxicity is not associated with increasing age [ 57 ].…”