Black Box Warning for Tendon Rupture
Ciprofloxacin carries a black box warning for tendon rupture. 1
Why Ciprofloxacin Has This Warning
The FDA drug label for ciprofloxacin explicitly addresses tendon rupture risk, particularly in geriatric patients, stating that "geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as Ciprofloxacin" and that this risk is "further increased in patients receiving concomitant corticosteroid therapy." 1
Fluoroquinolone Class Effect
While ciprofloxacin is the answer to your question, it's important to understand that all fluoroquinolones carry this black box warning, not just ciprofloxacin:
- Current fluoroquinolone use increases the odds of Achilles tendon rupture 4.1-fold (95% CI 1.8–9.6) compared to non-exposed individuals 2
- The absolute excess risk translates to approximately 12 additional Achilles tendon ruptures per 100,000 persons within 90 days of treatment 2, 3
- Levofloxacin specifically shows a 120% increased risk (HR=2.20; 95% CI 1.50 to 3.24) for Achilles tendon rupture within 30 days of use 4
Why the Other Antibiotics Do NOT Have This Warning
Azithromycin, doxycycline, amoxicillin, and cephalexin do not carry black box warnings for tendon rupture because they are not fluoroquinolones and lack the molecular mechanisms that cause tendon damage:
- Fluoroquinolones specifically inhibit cell proliferation and cause G2/M cell cycle arrest in tendon cells by down-regulating cyclin B 5
- They inhibit tenocyte spread and migration by down-regulating focal adhesion kinase phosphorylation 5
- They enhance matrix metalloproteinase-2 activity, leading to degradation of type I collagen 5
Important caveat: One large retrospective study found that cephalexin showed equal or greater risk than levofloxacin for tendon ruptures (HR=1.31; 95% CI 1.22 to 1.41), but this is likely due to confounding by indication bias rather than a true drug effect, and cephalexin does not have a black box warning. 4
High-Risk Populations Requiring Extra Caution
When prescribing ciprofloxacin or any fluoroquinolone, be especially vigilant in:
- Patients over 60 years: 4-fold higher risk of Achilles rupture (approximately 1 in 1,638 patients) 2, 3
- Concurrent corticosteroid users: Odds ratio of 43.2 for Achilles rupture (approximately 1 in 979 patients) 2, 3
- Athletes and physically active individuals: 50% of fluoroquinolone-associated tendon disorders occur during sports participation 2, 3
- Organ transplant recipients (kidney, heart, lung) 2
Clinical Presentation Timeline
- Median time to symptom onset: 6 days after starting ciprofloxacin 2
- Symptoms can appear as early as 2 hours or as late as 6 months after discontinuation 2, 3
- 90% of cases involve the Achilles tendon, but patellar tendon, rotator cuff, and elbow tendons can also be affected 6
- Bilateral involvement occurs in >50% of cases, so always examine both legs even if pain is unilateral 2, 7
Immediate Action Required
Discontinue ciprofloxacin immediately when any leg pain or tendon symptoms develop—progression to complete rupture can occur within 48 hours of symptom onset. 7