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Detecting Coadministered Drugs that Affect the Incidence of Long QT Syndrome Associated with Fluoroquinolone Antibiotics Using a Spontaneous Reporting System

Jun Matsuo, Satoshi Yamaori*, Kentaro Murai, Akira Mimura, Shigeru Ohmori

Background: Fluoroquinolone antibiotics (FQs) are known to induce long QT syndrome (LQTS). However, the combination of FQ and non-FQ drugs that elevate the incidence of LQTS has not been extensively studied. Here, we analyzed concomitant drugs that influence the risk of FQ-induced LQTS using a spontaneous reporting system.
Methods: We assessed adverse event reports in the Japanese Adverse Drug Event Report (JADER) database. The reporting odds ratio (ROR) and its 95% confidence interval (CI) were applied for signal detection. Furthermore, we evaluated the time-to-onset data for drug-related LQTS.
Results: The single use of garenoxacin, moxifloxacin, and ciprofloxacin was significantly associated with LQTS with RORs (95% CIs) of 3.16 (2.24 – 4.44), 7.65 (5.29 – 11.07), and 1.98 (1.06 – 3.70), respectively. The concomitant use of garenoxacin and disopyramide showed a much higher ROR of 884.18 (95% CI, 106.41 – 7346.92) than use of garenoxacin without disopyramide (ROR, 2.59; 95% CI, 1.78 – 3.78) and disopyramide without garenoxacin (ROR, 67.26; 95% CI, 54.18 – 83.49). The median time-to-onset for FQs alone (3.00 days) was significantly shorter than those for bepridil (49.00 days), disopyramide (26.50 days), clarithromycin (9.50 days), and famotidine
(11.00 days) (all p<0.001). In contrast, the time-to-onset of LQTS was not significantly different between single administration of FQs and coadministration of FQs and these four non-FQ drugs (4.00 days) (p=0.9363).
Conclusion: We identified drugs that may increase the risk of FQ-associated LQTS when coadministered. Attention is required to concomitant use of disopyramide with FQs, such as garenoxacin.