Fluoroquinolones are widely used broad‑spectrum antibiotics, but their association with tendinopathy and tendon rupture has become a major safety concern, particularly in weightbearing tendons such as the Achilles. This essay outlines the epidemiology, pathophysiology, clinical presentation, risk factors, and management of fluoroquinolone‑associated tendon injury, with particular attention to implications for lower‑limb practice.
Overview and epidemiology
Fluoroquinolones (FQs) such as ciprofloxacin, levofloxacin, and ofloxacin achieve excellent oral bioavailability and tissue penetration, and have therefore been heavily prescribed for urinary, respiratory, and gastrointestinal infections. Despite their efficacy, post‑marketing surveillance and observational studies have consistently linked these agents to tendinopathy and tendon rupture, prompting regulatory warnings in multiple countries.
Large database studies suggest that the absolute risk of tendon rupture with FQs is low but clinically meaningful. In a cohort of over 740,000 fluoroquinolone‑exposed patients, the excess risk attributable to current FQ use was estimated at about 3.7 additional tendon ruptures per 10,000 person‑years for any tendon rupture and 2.9 per 10,000 person‑years specifically for Achilles rupture. Another UK primary‑care database study reported an incidence of any tendon rupture of 5.9 per 10,000 person‑years, with Achilles tendon rupture at 1.9 per 10,000 person‑years, and found that FQ exposure increased the relative risk compared with a non‑FQ antibiotic comparator.
Relative risk estimates vary but generally demonstrate a 1.5–5‑fold increase in tendon rupture with current fluoroquinolone exposure, with higher estimates for Achilles tendon injuries. One nested case–control analysis reported odds ratios of 1.6 for any tendon rupture, 2.7 for Achilles rupture, and 1.5 for biceps rupture with current FQ use compared with non‑exposed patients. These data underpin the current view that, while population‑level risk is modest, the consequences for affected individuals can be severe and long‑lasting, especially in active or older adults.
Pathophysiology and mechanisms
The precise mechanism by which fluoroquinolones damage tendon tissue is not fully elucidated, but several converging pathways have been identified in experimental and translational studies. Tendons depend on a highly organised collagenous extracellular matrix maintained by tenocytes and other resident cells; disturbance of this balance predisposes to micro‑damage, degeneration, and, ultimately, mechanical failure.
In vitro and animal studies demonstrate that fluoroquinolones can impair fibroblast and tenocyte function by reducing collagen synthesis and up‑regulating matrix degradation. Ciprofloxacin, for example, has been shown to decrease type I collagen production and increase activity of matrix‑degrading enzymes, shifting the tendon milieu toward net catabolism. FQs also appear to increase apoptosis in human tenocytes, reducing the viable cell population needed for ongoing repair and homeostasis.
Another proposed mechanism relates to the chelating properties of fluoroquinolones, which bind divalent cations such as magnesium. This may disrupt cell–matrix interactions and interfere with integrin‑mediated signalling that is essential for mechanotransduction and collagen organisation. Histopathological studies of affected tendons have described hyaline and mucoid degeneration, chondroid metaplasia of tenocytes, altered mucopolysaccharide content, and disorganisation of collagen fibres, findings consistent with a degenerative tendinopathy rather than pure inflammatory process.
Vascular factors may further contribute. The Achilles tendon already has relatively poor blood supply, particularly in its mid‑portion, and this perfusion appears to decline with age. Reports of narrowed vasculature and paratendinous changes in FQ‑associated tendinopathy suggest that impaired blood flow and local ischaemia could exacerbate drug‑mediated matrix damage, helping explain the predilection for the Achilles in older patients. Together, changes in gene expression, cell survival, extracellular matrix composition, and microvascular supply create a vulnerable tendon prone to symptomatic tendinopathy and rupture under normal or modest mechanical loading.
Clinical features and risk factors
Fluoroquinolone‑associated tendon injury typically presents as an acute or subacute onset of pain, swelling, and stiffness in a tendon region within days to weeks of drug exposure, although onset can be delayed. The Achilles tendon is most commonly involved, accounting for nearly 90% of reported cases, but other sites such as the biceps brachii, supraspinatus, triceps, extensor pollicis longus, and various hand and shoulder tendons have also been described. Symptoms may be unilateral or bilateral and often include focal tenderness, impaired function, and difficulty with tasks that load the tendon (e.g., push‑off in gait or climbing stairs).
Several risk factors substantially amplify the likelihood of tendon injury in the setting of fluoroquinolone therapy. Advancing age is consistently associated with higher risk; epidemiological analyses show greater absolute risk in older adults, reflecting age‑related changes in tendon vascularity and matrix quality. Concomitant systemic corticosteroid therapy is a particularly potent enhancer, with studies indicating a materially increased risk of Achilles tendon rupture when FQs and steroids are used together compared with FQs alone. Other reported risk factors include chronic kidney disease and renal transplantation (with reduced drug clearance and higher tissue exposure), diabetes, and pre‑existing tendon disorders, as well as high levels of physical activity or sudden changes in loading.
From a podiatric perspective, a typical clinical scenario might involve an older patient treated with levofloxacin for pneumonia while on oral prednisolone for chronic obstructive pulmonary disease, presenting one to two weeks later with sudden posterior heel pain and difficulty weightbearing. If not recognised promptly and the antibiotic continued, this tendinopathy can progress to partial or complete rupture, often during relatively low‑demand activities such as walking.
Diagnosis and management
Diagnosis of fluoroquinolone‑associated tendinopathy is primarily clinical, based on a compatible symptom pattern, localisation to a tendon, and a history of recent or current FQ use in the absence of alternative causes. Ultrasound and MRI are not mandatory but can be valuable for confirming tendon involvement, characterising partial tears, and excluding other pathology, particularly for deep or less accessible tendons. Typical ultrasound features include tendon thickening, hypoechoic areas, and increased neovascularity on Doppler imaging, mirroring changes seen in non‑drug‑induced tendinopathy.
Once suspected, immediate cessation of the fluoroquinolone is recommended, even if the antibiotic course is incomplete, and an alternative non‑FQ agent should be selected whenever feasible. Early management centres on rest and load reduction for the affected tendon, often using heel lifts, counterforce bracing, walking aids, or short periods of immobilisation for Achilles involvement to reduce tensile stress. In Achilles cases, guidelines describe protecting the tendon for several weeks to months, with progressive re‑loading guided by pain and function.
Physical therapy plays a major role in rehabilitation once acute pain has settled. Protocols based on principles of connective tissue remodelling and eccentric loading, such as Alfredson’s heel‑drop programme, have been successfully adapted for FQ‑induced Achilles tendinopathy. Case reports describe meaningful improvements in pain and functional scores over 3–11 months with structured physiotherapy, sometimes combined with adjunctive modalities such as extracorporeal shockwave therapy when rest alone failed. Most cases of tendinosis recover over several weeks and typically within two months after discontinuation of the drug, although some patients experience more prolonged symptoms.
When tendon rupture occurs, management parallels that of non‑drug‑related ruptures and may be operative or non‑operative depending on patient factors, tendon involved, and local expertise. Early orthopaedic or sports medicine referral is appropriate, as delayed recognition can compromise outcomes. Importantly, individuals who have experienced fluoroquinolone‑associated tendon injury should generally avoid future exposure to this drug class, and prescribers should carefully evaluate the risk–benefit ratio before initiating FQs in patients with recognised risk factors.
Overall, fluoroquinolones exemplify the tension between antimicrobial efficacy and musculoskeletal safety. For clinicians working with the lower limb, recognising early tendon symptoms in patients recently treated with these agents, particularly older adults and those on corticosteroids, is critical to preventing progression from reversible tendinopathy to disabling rupture.