Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin

Pediatrics. 2014 Jul;134(1):e146-53. doi: 10.1542/peds.2013-3636. Epub 2014 Jun 2.


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.

Trial registration: NCT00210639.

Keywords: articular/growth and development; cartilage; fluoroquinolone toxicity; levofloxacin.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / toxicity*
  • Cartilage Diseases / chemically induced*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Levofloxacin / toxicity*
  • Male
  • Musculoskeletal Diseases / chemically induced
  • Prospective Studies
  • Time Factors


  • Anti-Bacterial Agents
  • Levofloxacin

Associated data