title: Risk of hepatotoxicity associated with fluoroquinolones: a national case-control safety study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.
authors.affiliation: Thamir M. Alshammari, Ph.D., is Assistant Professor, College of Pharmacy, Hail University, Saudi Arabia. E. Paul Larrat, Ph.D., is Dean, College of Pharmacy, University of Rhode Island (URI), Kingston; at the time of this study, he was Professor of Pharmacy, College of Pharmacy, URI. Haley J. Morrill, Pharm.D., is Clinical Research Outcomes Fellow in Antimicrobial Stewardship, Infectious Diseases Research Program, Providence Veterans Affairs Medical Center (VAMC), Providence, RI, and College of Pharmacy, URI. Aisling R. Caffrey, Ph.D., M.S., is Director of Outcomes Research, Infectious Diseases Research Program, Providence VAMC, and Assistant Professor of Pharmacoepidemiology, College of Pharmacy, URI. Brian J. Quilliam, Ph.D., is Associate Professor of Pharmacy, College of Pharmacy, URI. Kerry L. LaPlante, Pharm.D., is Associate Professor of Pharmacy, College of Pharmacy, URI; Director, Infectious Diseases Research Program, and Infectious Diseases Pharmacotherapy Specialist, Providence VAMC; and Adjunct Clinical Associate Professor of Medicine, Brown University, Providence.
authors.forename: Thamir M
authors.initials: TM
authors.lastname: Alshammari
authors.forename: E Paul
authors.initials: EP
authors.lastname: Larrat
authors.forename: Haley J
authors.initials: HJ
authors.lastname: Morrill
authors.forename: Aisling R
authors.initials: AR
authors.lastname: Caffrey
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Quilliam
authors.forename: Kerry L
authors.initials: KL
authors.lastname: LaPlante
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000453:epidemiology; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001372:Aza Compounds / Q000009:adverse effects; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D002939:Ciprofloxacin / Q000009:adverse effects; D015897:Comorbidity; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006787:Hospitals, Veterans; D006801:Humans; D064704:Levofloxacin / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D061214:Patient Safety; D011804:Quinolines / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D000077266:Moxifloxacin