title: Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study.
abstract: OBJECTIVE
  Fluoroquinolone-associated tendon ruptures are a recognised complication, but other severe collagen-associated adverse events may also be possible. Our objectives were to confirm the association of fluoroquinolones and tendon rupture, to clarify the potential association of fluoroquinolones and retinal detachment, and to test for a potentially lethal association between fluoroquinolones and aortic aneurysms.
  
  
  METHODS
  Population-based longitudinal cohort study in Ontario, Canada.
  
  
  METHODS
  Older adults turning 65 years between April 1 1997 and March 31 2012 were followed until primary outcome, death, or end of follow-up (March 31 2014). Fluoroquinolone prescriptions were measured as a time-varying covariate, with patients considered at risk during and for 30 days following a treatment course.
  
  
  METHODS
  Severe collagen-associated adverse events defined as tendon ruptures, retinal detachments and aortic aneurysms diagnosed in hospital and emergency departments.
  
  
  RESULTS
  Among the 1,744,360 eligible patients, 657,950 (38%) received at least one fluoroquinolone during follow-up, amounting to 22,380,515 days of treatment. The patients experienced 37,338 (2.1%) tendon ruptures, 3246 (0.2%) retinal detachments, and 18,391 (1.1%) aortic aneurysms. Severe collagen-associated adverse events were more common during fluoroquinolone treatment than control periods, including tendon ruptures (0.82 vs 0.26/100-person years, p<0.001), retinal detachments (0.03 vs 0.02/100-person-years, p=0.003) and aortic aneurysms (0.35 vs 0.13/100-person-years, p<0.001). Current fluoroquinolones were associated with an increased hazard of tendon rupture (HR 3.13, 95% CI 2.98 to 3.28; adjusted HR 2.40, 95% CI 2.24 to 2.57) and an increased hazard of aortic aneurysms (HR 2.72, 95% CI 2.53 to 2.93; adjusted HR2.24, 95% CI 2.02 to 2.49) that were substantially greater in magnitude than the association of these outcomes with amoxicillin. The hazard of retinal detachment was marginal (HR 1.28, 95% CI 0.99 to 1.65; adjusted HR 1.47, 95% CI 1.08 to 2.00) and not greater in magnitude than that observed with amoxicillin.
  
  
  CONCLUSIONS
  Fluoroquinolones are associated with subsequent tendon ruptures and may also contribute to aortic aneurysms.
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Nick
authors.initials: N
authors.lastname: Daneman
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada Division of General Internal Medicine, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Redelmeier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001014:Aortic Aneurysm / Q000453:epidemiology* / Q000209:etiology; D003094:Collagen / Q000009:adverse effects*; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D009864:Ontario; D012163:Retinal Detachment / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D013708:Tendon Injuries / Q000453:epidemiology* / Q000209:etiology
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D003094:Collagen
keywords: CLINICAL PHARMACOLOGY