Epidemiology of fluoroquinolone-associated tendon disorder
October 6, 2023
Prescription of fluoroquinolone antibiotics
To understand the extent of the side effects of fluoroquinolone antibiotics, we must first be aware of how frequently those drugs have been prescribed in the past, as well as how frequently they are prescribed today.
Although fluoroquinolones are considered reserve antibiotics, they were the most commonly prescribed antibiotics in the United States between 1995 and 2002.¹
Although there have been increased warnings regarding serious side effects of ciprofloxacin, levofloxacin, moxifloxacin, etc. in recent years, these substances are still frequently prescribed.
Just recently, the European Medicines Agency (EMA) reiterated that the implementation of the 2019 restrictions for non-life-threatening conditions has not been fully realized.²
Unfortunately, this is confirmed by our experience with many of those affected, whom we have consulted personally over the past few years. The risk is massively underestimated. Affected people are prescribed fluoroquinolone antibiotics for trivial infections or, even worse, as pure prophylaxis. Among others, I saw patients who were prescribed Cipro & Co. because of an uncomplicated bladder infection, a chronic prostatitis without bacterial confirmed bacterial infection or even because of a sty. These are certainly not the life- threatening conditions described by the EMA for an acceptable risk-benefit ratio when prescribing Cipro & Co.
Fluoroquinolones are still used too frequently in Europe today, as can be seen from the “Defined Daily Dose” per 1000 residents. While some countries like Denmark with a DDD per 1000 inhabitants of 0.3 do better, there are countries in the EU like Bulgaria with a DDD per 1000 inhabitants of 3.9.³
Epidemiology of fluoroquinolone-associated tendon disorders
The first report on fluoroquinolone-associated tendinopathy was published in 1983.¹
In that report, two patients presented with different tendinopathies, the first suffering from Achilles tendon tendinopathy and the second from bilateral tendinopathies of the finger flexors along with pain at the ankle and hip.¹
The first report of tendon rupture after administration of a fluoroquinolone antibiotic is in the literature in 1991.¹
In the United States, there was a black box warning regarding tendinitis and tendon rupture in 2008.¹ That warning represents the highest possible warning for any medication in the United States.(4)
The risk of tendonitis after Cipro, Levo, Moxi & Co. is significantly greater compared to treatment with other antibiotics. Cortisone administration and older age increase the risk in certain cases, but fluoroquinolone-associated tendon disorder also occurs in young patients and independently of cortisone co-administration.¹
The incidence of tendon disorder associated with fluoroquinolone antibiotic administration in a healthy population is “low” (approximately 0.14-0.4%)⁵ according to published data, but it is suspected that a very high incidence of unreported cases exists.
Achilles tendinopathy following fluoroquinolone exposure has been the most commonly reported to date, with almost half occurring bilaterally.5 However, other tendons may also be affected.
There are published case reports on the following tendon disorders:¹, ⁵
• Epicondylitis
• Finger tendons including thumb
• Patellartendon
• Supraspinatus tendon
• Quadriceps tendon
• Plantar fascia
• Tendinopathy ofthe subscapularis muscle
• Tendinopathy ofthe biceps brachii muscle
• Tendinopathy ofthe brachioradialis muscle
• Tendinopathy ofthe adductorlongus muscle
• Tendinopathy ofthe rectus femoris muscle
• Tendinopathy ofthe flexor hallucis longus muscle
• Tendinopathy ofthe extensor pollicis longus muscle
• Tendinopathy ofthe quadriceps muscle
How common are tendon ruptures caused by fluoroquinolones?
Achilles tendon rupture due to fluoroquinolones is associated with age, with patients over 60 being significantly more likely to suffer tendon ruptures.¹ The risk of tendinitis or rupture of other tendons is independent of age.¹ The risk for patients treated with fluoroquinolones to suffer a rupture is estimated by the authors to be 1 in 5958.¹ If one were to assume this figure, the high number of prescriptions of Cipro & Co. would result in a massive health policy problem, not even including the above-mentioned number of unreported cases.
Conclusion
Thus, the current literature shows a clear association between exposure to a fluoroquinolone antibiotic and the development of tendon disorder.¹
Too little common knowledge among professionals, in our opinion, is that a) fluoroquinolone antibiotics can lead to potentially long-term disability due to irreversible damage to tendons, b) tendinopathy does not develop only in elderly patients, c) tendon disease can occur regardless of the additional administration of cortisone, and d) virtually any tendon in the human body can be affected.
And this lack of knowledge is missing, although the FDA as well as the EMA have warned several times about long-term to irreversible and potentially disabling damage to tendons after treatment with a systemically active fluoroquinolone antibiotic. ², ⁶
This raises the question of whether better information options need to be established for practicing doctors in the future to ensure that such warnings reach their goal.
Marco Karrer B.Med
Many thanks for their cooperation: Andrea Gall (spelling), Ferdinand Dirsch (SEO, additions, translation into English), Michael Rosar (content, simplifications), Patrick Horisberger (content, simplifications),
First publication: 28.05.2023
Update 15.01.2023
Source:
- Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for usage in the Athletic Population
- Warnung EMA auf: https://www.ema.europa.eu/en/news/fluoroquinolone-antibiotics-reminder-measures-reduce-risk-long-lasting-disabling-potentially?
- Antimicrobial consumption in the EU/EEA (ESAC-Net) Annual Epidemiological Report for 2021, ECDC, https://www.ecdc.europa.eu/sites/default/files/documents/ESAC-Net_AER_2021_final-rev.pdf
- Cleveland Clinic, what does it mean if my medication has a black box warning; https:// health.clevelandclinic.org/what-does-it-mean-if-my-medication-has-a-black-box-warning/ #:~:text=Black%20box%20warnings%2C%20also%20called,safe%20use%20of%20the%20drug.
- Fluoroquinolone-Associated Tendinopathy: A Critical Review of the Literature; 2003; Khaliq and Zhanel
- FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together; 05.12.2026; https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug- safety-communication-fda-advises-restricting-fluoroquinolone-antibioticusecertain#:~:text=An%20FDA%20safety%20review%20has,nerves%2C%20and%20central%20ner
v ous%20system.
