What is the interaction between Levaquin (levofloxacin) and warfarin?

From the Guidelines

Levaquin (levofloxacin) and warfarin should not be used together without careful monitoring due to their potentially dangerous interaction. When these medications are combined, Levaquin can increase warfarin's anticoagulant effect, significantly raising the risk of bleeding complications, as fluoroquinolones like Levaquin can elevate the INR and increase the risk of adverse bleeding versus those taking warfarin alone 1. If a patient on warfarin requires Levaquin for an infection, the prescriber should consider alternative antibiotics when possible. If Levaquin is necessary, more frequent INR monitoring is essential, typically within 3-5 days of starting Levaquin and after completing the antibiotic course. Patients may require warfarin dose adjustments during and after Levaquin treatment. This interaction occurs because Levaquin can inhibit certain liver enzymes that metabolize warfarin, leading to higher warfarin blood levels. Additionally, both medications can independently increase bleeding risk. Patients taking both medications should be vigilant for signs of bleeding such as unusual bruising, nosebleeds, blood in urine or stool, and should seek immediate medical attention if these occur. Some key points to consider when using Levaquin and warfarin together include:

• Monitoring INR levels closely to avoid bleeding complications
• Considering alternative antibiotics to Levaquin when possible
• Adjusting warfarin doses as needed during and after Levaquin treatment
• Educating patients on the signs of bleeding and the importance of seeking immediate medical attention if they occur. It is crucial to prioritize careful monitoring and potential dose adjustments to minimize the risk of bleeding complications when using Levaquin and warfarin together, as supported by the most recent evidence 1.

From the FDA Drug Label

1. 2 Warfarin No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for R- and S-warfarin was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed However, there have been reports during the postmarketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see Adverse Reactions (6.3); Patient Counseling Information (17.4)].

Levaquin and Warfarin Interaction: Although a clinical study found no significant effect of levofloxacin on warfarin, there have been reports of levofloxacin enhancing the effects of warfarin, leading to episodes of bleeding.

• Key Considerations:
  • Closely monitor prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests.
  • Monitor patients for evidence of bleeding.
  • Inform patients to notify their physician if they are taking warfarin and to be monitored for evidence of bleeding 2.

From the Research

Interaction between Levaquin and Warfarin

• The interaction between Levaquin (levofloxacin) and warfarin has been studied in several research papers 3, 4, 5.
• A study published in 2003 found that the coadministration of levofloxacin and warfarin did not significantly affect the international normalized ratio (INR) in patients receiving warfarin therapy 3.
• However, another study published in 2002 reported four cases of hypoprothrombotic response resulting from the addition of levofloxacin therapy to chronic warfarin therapy, with significant increases in INR observed in all four cases 4.
• A retrospective medical record review published in 2006 compared anticoagulation-related outcomes in patients receiving stable dosages of warfarin who started levofloxacin or gatifloxacin therapy, and found that patients receiving warfarin who took gatifloxacin may be at higher risk for an INR above 4 compared with those taking levofloxacin 5.
• Other studies have also investigated the interaction between warfarin and other antibiotics, such as 5-fluorouracil 6 and cefixime 7.
• The results of these studies suggest that the interaction between Levaquin and warfarin can be significant, and that close monitoring of INR is recommended when these medications are used concomitantly 4, 5, 7.

Mechanism of Interaction

• The proposed mechanism of the interaction between levofloxacin and warfarin includes displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism 4.
• This interaction can lead to an increase in INR, which can increase the risk of bleeding complications 4, 5.

Clinical Implications

• The interaction between Levaquin and warfarin has important clinical implications, and healthcare providers should be aware of the potential for increased INR when these medications are used together 4, 5, 7.
• Close monitoring of INR and adjustment of warfarin dosage as needed can help to minimize the risk of bleeding complications 4, 5, 7.