Levofloxacin-associated tendon disorders: Sex-, age-, and route-specific disproportionality analysis using FAERS and JADER.

Abstract

This study evaluated the association between individual fluoroquinolones and tendon disorders in Japan using two spontaneous reporting systems: the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER). Five agents-ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin-were analyzed for "Muscle, tendon and ligament injuries" and "Tendon disorders." All fluoroquinolones showed positive signals in the FAERS, whereas only levofloxacin demonstrated consistent and robust associations in the Japanese subset of the FAERS and the JADER. In the JADER, levofloxacin exhibited strong signals for muscle, tendon, and ligament injuries (reporting odds ratio [ROR] 30.6, information component [IC] 4.5) and tendon disorders (ROR 134.2, IC 5.8). Stratified analysis revealed markedly stronger signals in males, particularly those aged ≥70 years (relative ROR 12.21 and 25.67; IC delta 3.18 and 2.85, respectively). Oral levofloxacin was associated with higher reporting odds than intravenous administration. Time-to-onset analysis indicated that most tendon-related adverse events occurred within 14 days after drug initiation. Levofloxacin exhibited the most consistent and robust association with tendon disorders, especially in males aged ≥70 years in Japan. Therefore, clinicians in Japan should exercise caution when prescribing levofloxacin to older male patients.