Comparative safety profile of levofloxacin in 2523 children with a focus on four specific musculoskeletal disorders.

Background: Fluoroquinolones, including levofloxacin, have not been recommended for use in children largely because studies in juvenile laboratory animals suggest there may be an increased risk of fluoroquinolone-associated cartilage lesions. A large prospective trial is needed to assess the risks associated with using levofloxacin in children. Objective: Assess the safety and tolerability of levofloxacin therapy in children based on observations for 1 year after therapy. Methods: Safety data were collected in children who participated in 1 of 3 efficacy trials (N = 2523) and a subset of these children who also subsequently participated in a long-term 1-year surveillance trial (N = 2233). Incidence of adverse events in children randomized to receive levofloxacin versus nonfluoroquinolone antibiotics was compared. Based on assessments by treating physicians and an independent data safety monitoring committee, events related to the musculoskeletal system were further categorized as 1 of 4 predefined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) considered most likely clinical correlates of fluoroquinolone-associated cartilage lesions observed in laboratory animals. Results: Levofloxacin was well tolerated during and for 1 month after therapy as evidenced by similar incidence and character of adverse events compared with nonfluoroquinolone antibiotics. However, incidence of at least 1 of the 4 predefined musculoskeletal disorders (largely due to reports of arthralgia) was greater in levofloxacin-treated compared with nonfluoroquinolone-treated children at 2 months (2.1% vs. 0.9%; P = 0.04) and 12 months (3.4% vs. 1.8%; P = 0.03) after starting therapy. Conclusions: The incidence of 1 or more of the 4 predefined musculoskeletal disorders identified in nonblinded, prospective evaluations, was statistically greater in levofloxacin-treated compared with comparator-treated children.