Why do quinolones (fluoroquinolones) cause tendinitis and peripheral neuropathy?

From the Guidelines

Quinolones cause tendinitis and peripheral neuropathy primarily through their effects on connective tissue and nerve cells, leading to oxidative stress and cell death, and this risk is increased in older adults, patients with kidney problems, those taking corticosteroids, and individuals with a history of tendon disorders 1.

Mechanism of Action

The mechanism by which quinolones cause tendinitis and peripheral neuropathy involves the disruption of collagen synthesis and the increase of matrix metalloproteinases that break down connective tissue, making tendons weaker and more prone to inflammation or rupture. Additionally, quinolones can damage the myelin sheath and axons of peripheral nerves through similar mitochondrial toxicity mechanisms, disrupting normal nerve function and causing symptoms like pain, numbness, and weakness.

Risk Factors

The risk of tendinitis and peripheral neuropathy associated with quinolone use is increased in certain patient populations, including:

• Older adults
• Patients with kidney problems
• Those taking corticosteroids
• Individuals with a history of tendon disorders
• Patients with a history of tendon damage or rupture

Clinical Implications

The risk of tendinitis and peripheral neuropathy associated with quinolone use is a significant concern, and these antibiotics should be used with caution in patients at high risk of these adverse effects. The FDA has issued black box warnings for quinolones, and they are typically reserved for serious infections when other antibiotics cannot be used 1.

Evidence-Based Recommendations

Based on the available evidence, quinolones should be used with caution in patients at high risk of tendinitis and peripheral neuropathy, and alternative antibiotics should be considered when possible 1. Additionally, patients should be monitored closely for signs and symptoms of tendinitis and peripheral neuropathy during and after quinolone treatment.

Key Points

• Quinolones can cause tendinitis and peripheral neuropathy through their effects on connective tissue and nerve cells
• The risk of these adverse effects is increased in older adults, patients with kidney problems, those taking corticosteroids, and individuals with a history of tendon disorders
• Quinolones should be used with caution in patients at high risk of tendinitis and peripheral neuropathy, and alternative antibiotics should be considered when possible
• Patients should be monitored closely for signs and symptoms of tendinitis and peripheral neuropathy during and after quinolone treatment 1

From the FDA Drug Label

Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. The FDA drug label does not answer the question.

From the Research

Quinolones and Tendinitis

• Quinolones, a class of antibiotics, have been associated with an increased risk of tendinitis and tendon rupture 2, 3, 4.
• The risk of tendon injury is higher in individuals over 60 years of age and those taking concomitant corticosteroids 2, 3, 4.
• Ofloxacin and levofloxacin have been found to possess higher propensities to cause tendon damage relative to other fluoroquinolones 2.
• The risk of tendon injury appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy 2.

Quinolones and Peripheral Neuropathy

• Quinolones have also been linked to peripheral neuropathy, a less frequently reported issue 5, 6.
• A case report presented a 42-year-old male who developed peripheral neuropathy several days after completing a 10-day course of ciprofloxacin for gastroenteritis 6.
• Nerve conduction studies and electromyography demonstrated peripheral neuropathy, and the patient was treated with intravenous immunoglobulin, steroids, and physical therapy 6.
• The potential combination of intravenous immunoglobulin and physical therapy has exhibited promising results in treating quinolone-induced peripheral neuropathy 6.

Risk Factors and Mechanisms

• Patient-specific risk factors for quinolone-associated tendinopathy include older age, receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation 2.
• The mechanisms underlying quinolone-induced tendinitis and peripheral neuropathy are not fully understood, but may involve the disruption of mitochondrial function and the induction of oxidative stress 5.
• Further research is needed to elucidate the underlying mechanisms and to develop effective therapeutic strategies for preventing and treating quinolone-induced tendinitis and peripheral neuropathy 5, 6.