What is the effect of Levofloxacin (a Fluoroquinolone) on International Normalized Ratio (INR) in a patient taking Coumadin (Warfarin)?

From the Guidelines

Levofloxacin may increase INR, so close monitoring during the course of treatment is warranted. When counseling the patient about coumadin and Levofloxacin use, the FNP should inform the patient that fluoroquinolones, such as Levofloxacin, can increase the International Normalized Ratio (INR) in patients taking warfarin (Coumadin), potentially increasing bleeding risk 1.

Key Considerations

• The interaction between Levofloxacin and warfarin can occur within the first week of combined therapy, and the risk persists throughout the course of Levofloxacin therapy and for several days afterward.
• More frequent INR monitoring is recommended, ideally within 3-5 days of starting the antibiotic.
• No specific dose adjustment of warfarin is recommended initially, but be prepared to reduce the warfarin dose based on INR results.
• Patients should be educated about signs of bleeding such as unusual bruising, nosebleeds, blood in urine or stool, and to seek immediate medical attention if these occur.

Mechanism of Interaction

The interaction occurs because Levofloxacin can inhibit the cytochrome P450 enzymes responsible for warfarin metabolism, particularly CYP1A2 and CYP3A4, and the antimicrobial effect of Levofloxacin can reduce vitamin K-producing gut bacteria, further enhancing warfarin's anticoagulant effect 1.

Clinical Implications

• The FNP should closely monitor the patient's INR levels and adjust the warfarin dose as needed to minimize the risk of bleeding.
• Patients should be aware of the potential interaction and report any signs of bleeding to their healthcare provider immediately.

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)].

Key Points:

• Levofloxacin may enhance the effects of warfarin, leading to increased risk of bleeding.
• Although clinical studies did not show a significant effect of levofloxacin on warfarin disposition, postmarketing reports suggest a potential interaction.
• Close monitoring of INR and prothrombin time is recommended when levofloxacin is administered concomitantly with warfarin.
• Patients should be monitored for evidence of bleeding 2.

The FNP should inform the patient that Fluoroquinolones may increase INR, so close monitoring during the course of treatment is warranted.

From the Research

Effect of Levofloxacin on INR in Patients Taking Coumadin

• The interaction between warfarin (Coumadin) and levofloxacin (a fluoroquinolone) has been studied in several research papers 3, 4, 5, 6.
• These studies suggest that levofloxacin may increase the International Normalized Ratio (INR) in patients taking warfarin, although the effect can be variable and inconsistent 3, 5, 6.
• Some patients may experience significant increases in INR, which can lead to bleeding complications 4, 5, 6.
• The proposed mechanism of this interaction is displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism 5.
• Close monitoring of INR is recommended when patients taking warfarin are started on levofloxacin therapy 3, 4, 6.

Clinical Implications

• Patients taking warfarin who are started on levofloxacin should be closely monitored for changes in INR 3, 4, 6.
• The risk of bleeding complications may be increased in these patients, and caution should be exercised when prescribing levofloxacin to patients taking warfarin 4, 5, 6.
• The effect of levofloxacin on INR can be significant, and patients should be educated on the importance of monitoring their INR regularly while taking both medications 3, 5, 6.