Third-generation fluroquinolones not linked to Achilles tendon ruptures
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The use of third-generation fluoroquinolones — specifically, garenoxacin, moxifloxacin, pazufloxacin, prulifloxacin and sitafloxacin — was not associated with an increased risk for Achilles tendon ruptures, a study in Japan showed.
Although prior studies have identified a relationship between first-generation (norfloxacin, nalidixic acid and pipemidic acid) and second-generation (ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin and tosufloxacin) fluoroquinolones and Achilles tendon ruptures, the evidence is less clear about the risks associated with third-generation fluoroquinolones, researchers wrote in Annals of Family Medicine.
Study co-author Takashi Chinen, MD, of the department of clinical oncology at Jichi Medical University in Tochigi, Japan, said he ruptured his right Achilles tendon shortly after taking levofloxacin, making the possibility of an association “an important issue” for him.
The researchers combed through Japan’s National Health Insurance and Elderly Health Insurance database and found 504 patients (median age, 64 years; 59% men) who ruptured an Achilles tendon within 30 days of receiving an antibiotic prescription. They labeled patients’ antibiotic use as either first- and second-generation fluoroquinolones, third-generation fluoroquinolones or nonfluoroquinolones.
“I expected no difference between older and newer fluoroquinolones,” Chinen said in the interview.
However, the researchers found that the risk for Achilles tendon rupture did not increase from exposure to third-generation fluoroquinolones (incidence rate ratio = 1.05; 95% CI, 0.33-3.37) and nonfluoroquinolones (incidence rate ratio = 1.08; 95% CI, 0.8-1.47). Conversely, the risk was elevated during exposure to first- and second-generation fluoroquinolones (incidence rate ratio = 2.94; 95% CI, 1.9-4.54). Stratifying the data by sex and recent corticosteroid use did not significantly impact the results.
The researchers wrote that their findings “may be useful” for clinicians who wish to tailor antibiotic treatments. Specifically, third-generation antibiotics “may be a safer option” for those who are at higher risk for Achilles tendon rupture (eg, athletes).
They said future studies with larger patient cohorts should look into whether third-generation fluoroquinolones are tied to rare adverse events like aortic aneurysm and dissection.
Perspective
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Corneilius "Neil" J. Clancy, MD
There has been an awful lot of attention given to fluoroquinolones’ toxicity, and the idea of changing antibiotic prescribing behavior has become a lot more prominent over the past couple of years. Regarding that latter point, my colleagues and I recently published a paper that indicated since the FDA placed warnings on fluoroquinolones regarding safety considerations, prescriptions for those antibiotics are down about 40% on the outpatient basis.
I am not particularly surprised by Chinen and colleagues’ findings. The association between fluoroquinolones and Achilles tendon rupture, although it is relatively rare, is a well-known red flag complication with the earlier generation fluoroquinolones. If you look at fluoroquinolones use, the early generation agents remain the warhorses. But given the potential for safety effects with fluoroquinolones, including tendon rupture, clinicians are usually better off avoiding those agents where possible. This study reiterates that admonition to clinicians.
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