From the Guidelines
Antibiotics can significantly increase the INR in patients taking warfarin, potentially leading to an increased risk of bleeding, and therefore, close monitoring of INR levels is crucial when initiating antibiotic therapy in these patients. Many antibiotics, particularly broad-spectrum agents like fluoroquinolones (ciprofloxacin, levofloxacin), macrolides (erythromycin, clarithromycin), metronidazole, trimethoprim-sulfamethoxazole, and some cephalosporins, can significantly elevate INR values 1. This interaction occurs through several mechanisms: antibiotics can disrupt intestinal flora that produce vitamin K, directly inhibit vitamin K-dependent clotting factor synthesis, or interfere with warfarin metabolism through the cytochrome P450 system.
Some key points to consider when managing patients on warfarin who require antibiotic therapy include:
- Close monitoring of INR levels, typically within 3-5 days of starting the antibiotic therapy 1
- Dose adjustments of warfarin may be necessary based on these INR results 1
- Patients should be educated about signs of bleeding such as unusual bruising, nosebleeds, blood in urine or stool, and excessive menstrual bleeding
- Some antibiotics with lower interaction potential include azithromycin and tetracyclines, which might be preferred when appropriate for the infection being treated 1
- Pre-emptive warfarin dose reductions of 25% and 33% for sulfamethoxazole and metronidazole respectively, are recommended when co-administered with warfarin 1
It is essential to note that the severity of the interaction between antibiotics and warfarin can vary depending on the specific antibiotic used, the dose, and the duration of therapy 1. Therefore, healthcare providers should be aware of these potential interactions and take necessary precautions to minimize the risk of bleeding in patients taking warfarin.
From the FDA Drug Label
The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: ... (fluoroquinolones) ... trimethoprim/sulfamethoxazole
The following factors, alone or in combination, may be responsible for DECREASED PT/INR response: ...
Antibiotics can affect INR in patients on warfarin.
- Some antibiotics, such as fluoroquinolones and trimethoprim/sulfamethoxazole, may increase the PT/INR response.
- No information is provided about the effect of all antibiotics on INR in patients on warfarin. 2
From the Research
Effect of Antibiotics on INR in Patients on Warfarin
- The interaction between antibiotics and warfarin can lead to an increase in international normalized ratio (INR) levels, potentially causing bleeding complications 3, 4, 5, 6.
- Studies have shown that certain antibiotics, such as levofloxacin, moxifloxacin, and ciprofloxacin, can significantly increase INR levels in patients on warfarin therapy 3, 5, 6.
- The proposed mechanisms of this interaction include displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism 3.
- However, not all antibiotics have a significant effect on INR levels, and some studies have found no significant difference in INR values before and after antibiotic administration 7.
- Factors that can increase the risk of excessive anticoagulation include cancer diagnosis, elevated baseline INR, and female sex 4.
- Close monitoring of INR levels is recommended when prescribing antibiotics to patients on warfarin therapy, especially in older adults 5.
Specific Antibiotics and Their Effects on INR
- Levofloxacin has been shown to increase INR levels in patients on warfarin therapy 3, 5, 6.
- Moxifloxacin has also been found to increase INR levels in patients on warfarin therapy 5, 6.
- Ciprofloxacin has been shown to increase INR levels in patients on warfarin therapy 5.
- Cefixime has been found to have no significant effect on INR levels in patients on warfarin therapy 6.
- Amoxicillin and azithromycin have also been found to increase INR levels in patients on warfarin therapy 5.