the findings of a new study suggest.
If confirmed, this will be good news for patients who are allergic to beta-lactam antibiotics and others in whom fluoroquinolones are the antibiotics of choice because of their favorable pharmacokinetic properties and broad-spectrum activity, according to Dr. Takashi Chinen of Jichi Medical University in Tochigi, Japan, lead investigator of the new study, published in Annals of Family Medicine.
“This is especially notable for patients who are at increased risk for tendon disorders, such as athletes,” Dr. Chinen said in an interview.
To investigate the association between third-generation fluoroquinolones and tendinopathy, Dr. Chinen and colleagues conducted a self-controlled case series analysis using administrative claims data for a single prefecture in Japan, focusing specifically on the risk of Achilles tendon rupture.
From a database of 780,000 residents in the Kumamoto Prefecture enrolled in the country’s National Health Insurance and Elderly Health Insurance from April 2012 to March 2017, the investigators identified 504 patients who experienced Achilles tendon rupture during the 5-year period and were prescribed an antibiotic at some time during that period. They divided the observation period into antibiotic exposure (30 days from prescription) and nonexposure periods based on previous research linking this fluoroquinolone exposure window to an elevated risk of tendon injury. They classified antibiotics into fluoroquinolones and nonfluoroquinolones and further classified the fluoroquinolones by first, second, and third generation, including the following agents:
- First generation: Norfloxacin, nalidixic acid, pipemidic acid
- Second generation: Levofloxacin, tosufloxacin, ciprofloxacin, ofloxacin, lomefloxacin
- Third generation: Garenoxacin, sitafloxacin, prulifloxacin, moxifloxacin, pazufloxacin.
Tendon rupture risk varied based on fluoroquinolone class
Comparing the incidence of Achilles tendon rupture in the exposure period relative to the nonexposure period, the risk of rupture was not elevated during exposure to third-generation fluoroquinolones (incidence rate ratio, 1.05; 95% confidence interval, 0.33-3.37) and nonfluoroquinolones (IRR, 1.08; 95% CI, 0.80- 1.47). Contrasting with those findings, the researchers found that the risk of tendon rupture was significantly elevated during exposure to first- and second-generation fluoroquinolones (IRR, 2.94; 95% CI, 1.90-4.54). Similar findings were observed in subgroup analyses by gender and recent corticosteroid use, the authors wrote.
The increased risk associated with exposure to first- and second-generation fluoroquinolones is consistent with the elevated risk observed in previous studies, the majority of which focused on first- and second-generation agents, the authors noted.
“Our study is the first to investigate the risk of Achilles tendon rupture associated with third-generation fluoroquinolones by self-controlled case series analysis and using a large administrative claims database,” they said.
Because the study is based on administrative claims data, it does not support conclusions about differential risks.
“Some preclinical studies suggest that structural differences [in the drugs] may affect the risks,” Dr. Chinen said. In particular, one preclinical study linked methylpiperazinyl substituent with increased risk of tendon injury, and this substituent is more common in first- and second-generation fluoroquinolones.