title: Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study.
abstract: BACKGROUND
  Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4.
  
  
  OBJECTIVE
  To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.
  
  
  METHODS
  Population-based cohort study.
  
  
  METHODS
  Ontario, Canada, from 2003 to 2010.
  
  
  METHODS
  Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478).
  
  
  METHODS
  The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.
  
  
  RESULTS
  Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]).
  
  
  CONCLUSIONS
  Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive.
  
  
  CONCLUSIONS
  In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.
  
  
  BACKGROUND
  Academic Medical Organization of Southwestern Ontario.
authors.affiliation: Western University and Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Patel
authors.forename: Salimah
authors.initials: S
authors.lastname: Shariff
authors.forename: David G
authors.initials: DG
authors.lastname: Bailey
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
authors.forename: Sonja
authors.initials: S
authors.lastname: Gandhi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mamdani
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.forename: Jamie
authors.initials: J
authors.lastname: Fleet
authors.forename: Y Joseph
authors.initials: YJ
authors.lastname: Hwang
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017963:Azithromycin / Q000009:adverse effects; D002423:Cause of Death; D017291:Clarithromycin / Q000009:adverse effects; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004917:Erythromycin / Q000009:adverse effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000097:blood; D008297:Male; D012189:Retrospective Studies; D012206:Rhabdomyolysis / Q000139:chemically induced*
chemical_list: D000900:Anti-Bacterial Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin