Risk of Acute Liver Injury Associated with the Use of Moxifloxacin and Other Oral Antimicrobials: A Retrospective, Population-Based Cohort Study

Authors


  • Bayer Pharma AG provided funding to RTI Health Solutions to conduct this study. The contract between RTI Health Solutions and Bayer for the conduct of this study grants the research team all decisions regarding the content of the publication of the results.
  • Results of this study were presented in part at the 28th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, August 23–26, 2012, Barcelona, Spain.
  • ClinicalTrials.gov Identifier: NCT01434173.
  • [Correction added on 7 April 2014, after first online publication: copyright line has been updated.]

Abstract

Study Objective

To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials—amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin—compared with nonusers of these antimicrobials.

Design

Retrospective, observational cohort study with a nested case-control analysis.

Data Source

HealthCore Integrated Research Database.

Patients

Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use.

Measurements and Main Results

Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29–42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6–6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8–5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3–5.0), doxycycline (2.5, 95% CI 1.2–5.2), moxifloxacin (2.3, 95% CI 1.1–4.7), and amoxicillin (2.3, 95% CI 1.1–4.7).

Conclusion

The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.

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