Is there a black box warning for taking Levaquin (levofloxacin) and prednisone together?

Black Box Warning for Concurrent Use of Levaquin and Prednisone

Yes, there is a black box warning for taking Levaquin (levofloxacin) and prednisone together due to significantly increased risk of tendon rupture. 1

The Warning and Risk Factors

The FDA black box warning for levofloxacin specifically states that fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased by:

• Age over 60 years
• Concurrent use of corticosteroids (like prednisone)
• History of kidney, heart, or lung transplants 1

Evidence for Increased Risk

The combination of levofloxacin and corticosteroids presents a particularly high risk:

• Corticosteroids are specifically mentioned in the black box warning as a factor that increases tendon rupture risk 1
• Studies show that levofloxacin has a higher propensity for causing tendon damage compared to other fluoroquinolones 2
• Surveillance data from the FDA's Adverse Event Reporting System found levofloxacin had the highest signal for tendon rupture among fluoroquinolones (EBGM = 55.2) 3
• Approximately 21.2% of tendon rupture cases associated with fluoroquinolones involved concomitant corticosteroid use 3

Clinical Presentation and Onset

• Tendon injuries can occur during or after fluoroquinolone treatment
• There may be a latency period between starting levofloxacin and the onset of tendinopathy symptoms 4
• Symptoms include pain, swelling, inflammation, and in severe cases, complete rupture of tendons (particularly the Achilles tendon)
• These injuries can result in chronic pain, mobility restrictions, and may require surgery 2

Risk Stratification

The risk of tendinopathy is highest in patients with multiple risk factors:

1. Highest risk: Patients over 60 years taking both levofloxacin and prednisone, especially with renal dysfunction 4
2. Moderate risk: Patients with one risk factor (either age >60, corticosteroid use, or renal dysfunction)
3. Lower risk: Younger patients without other risk factors

Clinical Recommendations

When considering this combination:

• Avoid concurrent use of levofloxacin and prednisone whenever possible, especially in high-risk patients
• If treatment is absolutely necessary, consider:
  • Using an alternative antibiotic class if clinically appropriate
  • Using the lowest effective dose and shortest duration of both medications
  • Monitoring closely for signs of tendon pain or inflammation
  • Discontinuing levofloxacin immediately if tendon pain, swelling, or inflammation occurs

Alternative Approaches

When treating infections in patients requiring corticosteroids:

• Consider non-fluoroquinolone antibiotics based on the infection site and suspected pathogens:
  • Respiratory infections: Amoxicillin/clavulanate, macrolides, or cephalosporins 5
  • Urinary tract infections: Trimethoprim-sulfamethoxazole, nitrofurantoin, or cephalosporins
  • Skin infections: Cephalosporins, amoxicillin/clavulanate

Conclusion

The black box warning for the combination of levofloxacin and prednisone is significant and should prompt careful consideration of alternative treatment options whenever possible. When the combination cannot be avoided, patients should be closely monitored and educated about the risk of tendon injury.