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: John S Bradley, Ralph E Kauffman, Dainius A Balis, Ciaran M Duffy, Peter G Gerbino, Samuel D Maldonado, Gary J Noel
• Journal: Pediatrics (Pediatrics) Vol. 134 Issue 1 Pg. e146-53 (Jul 2014) ISSN: 1098-4275 [Electronic] United States
• PMID: 24918220 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright © 2014 by the American Academy of Pediatrics.

Chemical References

• Anti-Bacterial Agents
• Levofloxacin

Topics

• 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