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

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.