Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin

• Published in: Pediatrics (Evanston) 2014-07, Vol.134 (1), p.e146-e153
• Main Authors: Bradley, John S, Kauffman, Ralph E, Balis, Dainius A, Duffy, Ciaran M, Gerbino, Peter G, Maldonado, Samuel D, Noel, Gary J
• Format: Article
• Language: English
• Subjects: Adolescent; Anti-Bacterial Agents - toxicity; Cartilage; Cartilage Diseases - chemically induced; Child; Child, Preschool; Children & youth; Comparative analysis; Complications and side effects; Dosage and administration; Female; Follow-Up Studies; Humans; Infant; Injuries; Levofloxacin; Levofloxacin - toxicity; Male; Medical treatment; Musculoskeletal diseases; Musculoskeletal Diseases - chemically induced; Pediatrics; Prospective Studies; Risk factors; Time Factors
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2013-3636

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. 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. 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. 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.