Can ciprofloxacin (Cipro) cause leg pain or tendon injury?

Can Ciprofloxacin Cause Leg Pain?

Yes, ciprofloxacin definitively causes leg pain through tendon damage, particularly affecting the Achilles tendon, and this is a serious adverse effect that requires immediate discontinuation of the medication. 1

Mechanism and Incidence

Ciprofloxacin and other fluoroquinolones cause musculoskeletal complications through multiple mechanisms:

• Tendon damage occurs in 0.14% to 0.4% of patients taking fluoroquinolones, with the Achilles tendon being the most commonly affected site (90% of tendon cases). 2
• The drug induces collagen-degrading enzymes that cause direct tendon damage and ischemia in poorly vascularized regions, preventing normal repair. 3
• Current use of ciprofloxacin increases the odds ratio for Achilles tendon rupture to 4.1 (95% CI, 1.8-9.6). 4
• The absolute risk is approximately 12 additional cases of Achilles tendon rupture per 100,000 persons within 90 days of treatment. 5

Timeline of Symptoms

Leg pain typically develops rapidly after starting ciprofloxacin:

• Median onset is 6 days after starting the medication. 5
• Symptoms can appear as early as 2 hours after the first dose. 6, 7
• Pain may develop up to 6 months after discontinuation of the drug. 8
• In one documented case, severe Achilles tendon pain developed within 3 days of starting ciprofloxacin (after only 3 grams total). 6

High-Risk Populations

The FDA drug label and clinical guidelines identify specific risk factors that dramatically increase the likelihood of leg pain and tendon injury: 1

• Age over 60 years: 4 times higher risk of Achilles tendon rupture compared to general population, with 1 in 1,638 patients experiencing rupture. 4, 9
• Concomitant corticosteroid use: Increases odds ratio to 43.2 for Achilles tendon rupture (1 in 979 patients). 4, 8
• Organ transplant recipients (kidney, heart, or lung). 5
• Pre-existing conditions: Rheumatoid arthritis, osteoarthritis, kidney failure, or previous tendon problems. 4, 9, 1
• Athletes and physically active individuals: 50% of fluoroquinolone-associated tendon disorders occur during sports participation. 8

Clinical Presentation Beyond Achilles Tendon

While Achilles tendon pain is most common, ciprofloxacin causes pain in other leg structures:

• Patellar tendon involvement occurs in approximately 10% of non-Achilles cases. 8
• Gluteal tendon tendinopathy causing hip pain has been documented. 2
• Hamstring tendon avulsion from the ischial tuberosity causing posterior thigh pain. 3
• Bilateral involvement occurs in more than 50% of cases, so both legs must be examined even if pain is initially unilateral. 5, 8
• Severe generalized myalgia (muscle pain) throughout the legs can occur without elevated muscle enzymes or rhabdomyolysis. 10

Immediate Management Algorithm

When leg pain develops during or after ciprofloxacin use:

1. Stop ciprofloxacin immediately - tendon damage can progress to complete rupture within 48 hours of symptom onset. 8
2. Do not resume fluoroquinolone therapy in patients with previous fluoroquinolone-associated tendon disorders. 8
3. Examine both legs bilaterally for tendon involvement, even if symptoms are unilateral. 8
4. Avoid all physical activity and weight-bearing on the affected limb until tendinitis or rupture is ruled out. 1
5. Do not combine NSAIDs with corticosteroids for pain control, as this further increases rupture risk. 8

Protective Measures

For patients who must take ciprofloxacin despite risks, the American College of Physical Medicine and Rehabilitation recommends:

• Magnesium supplementation during the treatment course if no contraindications exist (ciprofloxacin chelates magnesium, potentially affecting collagen synthesis). 8
• Antioxidant supplementation with vitamin E or coenzyme Q10 may provide protective effects against tendon damage. 8
• One case report documented low intracellular ATP and coenzyme Q10 levels in a patient with ciprofloxacin-induced disability, suggesting mitochondrial damage. 6

Prognosis

Most patients who discontinue ciprofloxacin report clinical improvement within 2 months, though 26% may still report pain and disability at follow-up. 8 However, the FDA label warns that tendon ruptures have occurred up to several months after patients finished taking fluoroquinolones. 1

Critical Pitfall

The American Academy of Pediatrics found that ciprofloxacin showed musculoskeletal adverse event rates of 9.3% versus 6.0% in control patients, demonstrating that this is not a rare occurrence. 4 Physicians must maintain high clinical suspicion for fluoroquinolone-induced leg pain, as assuming symptoms will resolve without discontinuing the drug leads to poor outcomes and potential permanent disability. 8