Quinolones and Steroids Significantly Increase Risk of Deep Tendon Rupture
The combination of quinolones (fluoroquinolones) and corticosteroids dramatically increases the risk of tendon rupture, with an odds ratio of 43.2 (95% CI, 5.5-341.1) specifically for Achilles tendon rupture compared to fluoroquinolone use alone. 1
Risk Quantification
- Fluoroquinolones alone increase the risk of tendon disorders (odds ratio 1.7), tendon rupture (odds ratio 1.3), and specifically Achilles tendon rupture (odds ratio 4.1) 1
- When fluoroquinolones are combined with corticosteroids, the risk increases dramatically for both tendon rupture (odds ratio 3.1) and specifically Achilles tendon rupture (odds ratio 43.2) 1
- In absolute terms, approximately 1 in 5,958 patients treated with fluoroquinolones alone will experience Achilles tendon rupture 1, 2
- With concomitant corticosteroid use, this risk increases to 1 in 979 patients experiencing Achilles tendon rupture 1, 2
- The absolute increase in risk is about 12 cases of Achilles tendon rupture per 100,000 persons within 90 days of fluoroquinolone treatment 1, 3
Risk Factors That Further Increase Tendon Rupture Risk
- Age over 60 years: Significantly increases risk, with 4 times higher risk of Achilles tendon rupture compared to the general population 1, 3
- When stratified by age, 1 Achilles tendon rupture per 1,638 fluoroquinolone-treated patients older than 60 years could be expected 1
- For elderly patients taking both fluoroquinolones and corticosteroids, the risk is substantially higher with an adjusted rate difference of 19.6 for any tendon rupture per 10,000 patients 4
- Non-obesity: Surprisingly, non-obese individuals have a higher risk (OR 7.7) compared to obese individuals (OR 2.4) 5
- Female sex: Women appear to have a higher risk (OR 5.0) compared to men (OR 3.6) 5
- Participation in sports: 50% of tendon disorders in fluoroquinolone users occurred during sports participation 1
Timing of Tendon Rupture Risk
- Symptoms typically occur within 1 week of exposure to fluoroquinolones (median 6 days) 1, 3
- The risk is highest within the first 30 days following exposure to fluoroquinolones 1, 4
- Risk can persist for up to 60 days after fluoroquinolone exposure 4
- In rare cases, symptoms can appear as early as 2 hours after initial exposure or as late as 6 months after discontinuation 3
Affected Tendons
- While the Achilles tendon is most commonly affected (90% of cases), other tendons may also be involved 1, 3
- Other affected tendons include patellar tendon, rotator cuff, common flexor and extensor tendons at the elbow 1
- In more than half of Achilles tendon cases, both tendons are affected bilaterally 1
FDA Warnings and Recommendations
- The FDA has issued a boxed warning that "fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture in all ages" 6
- This risk is "further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants" 6
- For geriatric patients, the FDA label specifically states: "Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy." 7
Potential Mitigation Strategies
- Consider magnesium supplementation during fluoroquinolone treatment if no contraindications exist 8
- For high-risk individuals (over 60 years, history of tendon disorders, athletes), consider alternative antibiotic classes when clinically appropriate 8
- Patients should be informed of this potential side effect and advised to discontinue the fluoroquinolone and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur 7
- Avoid unnecessary physical activity, particularly sports participation, during fluoroquinolone treatment, especially in high-risk individuals 1