Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study.

PURPOSE: Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported.

METHODS: In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables.

RESULTS: After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk.

CONCLUSION: The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.