Female sex and discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis

Abstract

Objectives: To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study.

Methods: The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007-September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression.

Results: Of 1306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5-50.0%) completed treatment and 196 (15.0%, 95% CI 13.1-17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32-2.10, p < 0.001) and current alcohol use (RR 1.41, 95% CI 1.13-1.77, p = 0.003) were independently associated with isoniazid discontinuation due to adverse effects.

Conclusions: The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects.

Keywords: Adverse effects; Alcohol use; Female sex; Latent tuberculosis infection; Mycobacterium tuberculosis.