Fluoroquinolones Cause Achilles Tendon Rupture
Fluoroquinolone antibiotics, particularly ciprofloxacin and levofloxacin, are the antibiotics most strongly associated with Achilles tendon rupture, carrying a black box FDA warning for this serious complication. 1
The Fluoroquinolone Class
Fluoroquinolones as a class increase the risk of Achilles tendon rupture with an odds ratio of 4.1 compared to non-users. 2, 3 The FDA issued a black box warning in 2008 for all fluoroquinolones citing increased risk of tendinitis and tendon rupture. 4
Specific fluoroquinolones implicated include:
- Ciprofloxacin - most commonly prescribed and most frequently reported in case series 1, 5, 6
- Levofloxacin - shows 120% increased risk (HR 2.20) for Achilles tendon rupture within 30 days of use 7, 8
- Ofloxacin - demonstrated highest risk in multiple observational studies 9
- Moxifloxacin - also carries the class warning 7
Risk Quantification
The absolute risk is approximately 12 additional cases of Achilles tendon rupture per 100,000 persons within 90 days of fluoroquinolone treatment. 2, 3 The Achilles tendon is affected in 90% of fluoroquinolone-associated tendon ruptures, with bilateral involvement occurring in more than half of cases. 3
High-Risk Populations Requiring Extreme Caution
Age over 60 years: 4-fold increased risk compared to general population, with 1 rupture expected per 1,638 treated patients. 2, 10
Concomitant corticosteroid use: Dramatically escalates risk to odds ratio of 43.2 for Achilles tendon rupture (1 rupture per 979 patients). 3, 10
Other high-risk factors include: 1
- Kidney, heart, or lung transplant recipients
- History of tendon disorders or rheumatoid arthritis
- Renal failure
- Active participation in sports or strenuous physical activity
- Osteoarthritis 10
Timing of Rupture
Symptoms typically occur within 1 week of exposure (median 6 days), but can appear as early as 2 hours after the first dose or as late as 6 months after discontinuation. 2, 3 The highest risk period is within the first 30 days following exposure. 3
Mechanism of Toxicity
Fluoroquinolones chelate magnesium and other divalent cations, leading to reduced collagen type I, elastin, and fibronectin in tendons. 4 They also increase matrix metalloproteinase-3 (MMP-3) expression, induce apoptosis in tendon cells, and disrupt integrin-mediated cell signaling pathways critical for tendon integrity. 4
Critical Management Points
Discontinue the fluoroquinolone immediately at the first sign of tendon pain, swelling, or inflammation. 1 Patients should rest and avoid weight-bearing activities. 1
Consider magnesium supplementation during fluoroquinolone treatment if no contraindications exist, as recommended by the American College of Physical Medicine and Rehabilitation. 2
For high-risk individuals (over 60 years, corticosteroid users, athletes, transplant recipients), strongly consider alternative antibiotic classes when clinically appropriate. 2, 10
Common Pitfall
Do not assume tendon symptoms are simply musculoskeletal strain—fluoroquinolone-associated tendinopathy can progress rapidly to complete rupture if the antibiotic is continued. 1 MRI is useful to distinguish between tendinitis and partial rupture when clinical examination is equivocal. 5