Fluoroquinolone Exposure and Other Factors Associated with Achilles Tendon Rupture: A Nationwide Nested Case–Control Study

Background/Objectives: Fluoroquinolones have been associated with tendon disorders, including Achilles tendon rupture (ATR). We investigated the associations of individual fluoroquinolone prescriptions and patient characteristics with ATR in a nationwide Korean claims dataset. Methods: This nested case–control study used Korean National Health Insurance Service data from 2009 to 2019. We included 40,240 ATR cases identified by KCD code S86.0 and 160,960 risk-set-sampled controls. Exposure was defined as a fluoroquinolone prescription lasting more than six days within 180 days before the index date. Poisson regression described population rates; unconditional multivariable logistic regression estimated adjusted odds ratios (aORs). Results: The overall incidence of ATR was 29.1 per 100,000 persons and increased during the study period. Levofloxacin prescriptions were associated with higher odds of ATR (aOR 1.28, 95% CI 1.13–1.44). In age-stratified analyses, the levofloxacin estimate was 1.08 (95% CI 0.82–1.41), 1.25 (1.07–1.46), and 1.66 (1.23–2.23) in those aged 23–39, 40–64, and ≥65 years, respectively; interaction was not formally tested. Higher BMI (30–34.9 kg/m2: aOR 2.20, 95% CI 2.09–2.32) and other patient characteristics were also associated with ATR in the overall sample. Conclusions: Levofloxacin exposure was associated with ATR, particularly in older adults, although outcome specificity, exposure classification, residual confounding, and incomplete accounting for matching limit causal interpretation. The data do not establish the comparative safety of other fluoroquinolones or fluoroquinolone-specific effects of patient characteristics.