title: Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin.
abstract: BACKGROUND
  Safety concerns for fluoroquinolones exist from animal studies demonstrating cartilage injury in weight-bearing joints, dependent on dose and duration of therapy. For children treated with levofloxacin or comparator in randomized, prospective, comparative studies for acute otitis media and community-acquired pneumonia, this 5-year follow-up safety study was designed to assess the presence/absence of cartilage injury.
  
  
  METHODS
  Children enrolled in treatment studies were also enrolled in a 1-year follow-up safety study, which; focused on musculoskeletal adverse events (MSAE). Those with persisting MSAEs, protocol-defined musculoskeletal disorders, or of concern to the Data Safety and Monitoring Committee were requested to enroll in four additional years of follow-up, the subject of this report.
  
  
  RESULTS
  Of the 2233 subjects participating in the 12-month follow-up study, 124 of 1340 (9%) of the levofloxacin subjects, and 83 of 893 (9%) of the comparator subjects were continued for 5-year posttreatment assessment. From children identified with an MSAE during years 2 through 5 posttreatment, the number that were "possibly related" to drug therapy was equal for both arms: 1 of 1340 for levofloxacin and 1 of 893 for comparator. Of all cases of MSAE assessed by the Data Safety and Monitoring Committee at 5 years' posttreatment, no case was assessed as "likely related" to study drug.
  
  
  CONCLUSIONS
  With no clinically detectable difference between levofloxacin- and comparator-treated children in MSAEs presenting between 1 and 5 years in these safety studies, risks of cartilage injury with levofloxacin appear to be uncommon, are clinically undetectable during 5 years, or are reversible.
authors.affiliation: University of California, San Diego School of Medicine and Rady Children's Hospital San Diego, San Diego, California; jbradley@rchsd.org.
authors.forename: John S
authors.initials: JS
authors.lastname: Bradley
authors.affiliation: Children's Mercy Hospitals and Clinics and University of Missouri at Kansas City, Kansas City, Missouri;
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Kauffman
authors.affiliation: Janssen Research and Development, LLC, Raritan, New Jersey;
authors.forename: Dainius A
authors.initials: DA
authors.lastname: Balis
authors.affiliation: Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada;
authors.forename: Ciaran M
authors.initials: CM
authors.lastname: Duffy
authors.affiliation: Community Hospital of the Monterey Peninsula; Monterey, California; and.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gerbino
authors.affiliation: Janssen Research and Development, LLC, Raritan, New Jersey;
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Maldonado
authors.affiliation: Janssen Research and Development, LLC, Raritan, New Jersey;Weill Cornell Medical College, New York, New York.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Noel
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002357:Cartilage Diseases / Q000139:chemically induced*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D064704:Levofloxacin / Q000633:toxicity*; D008297:Male; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: articular/growth and development; cartilage; fluoroquinolone toxicity; levofloxacin