What antibiotics are compatible with warfarin (anticoagulant) therapy?

From the Guidelines

Antibiotics such as penicillins, cephalosporins, and macrolides like azithromycin are generally considered safer options to use with warfarin, though careful monitoring is recommended. When considering the use of antibiotics in patients on warfarin therapy, it is crucial to understand the potential interactions that can affect the patient's morbidity, mortality, and quality of life. The most recent and highest quality study, published in 2022 in the journal Circulation: Arrhythmia and Electrophysiology 1, highlights the importance of monitoring INRs closely when antibiotics are initiated in patients on chronic warfarin use.

Key Considerations

• All antibiotics can alter the gut microbiome, potentially potentiating anticoagulant effects of warfarin 1.
• Antibiotics that inhibit the CYP2C9 isoenzyme, such as sulfonamides and metronidazole, can further exacerbate this interaction, increasing the risk of serious bleeding 1.
• Pre-emptive warfarin dose reductions may be necessary when co-administering certain antibiotics, such as sulfamethoxazole and metronidazole, with warfarin 1.

Safer Antibiotic Options

• Penicillins (e.g., amoxicillin)
• Cephalosporins (e.g., cefuroxime and cefazolin)
• Macrolides (e.g., azithromycin)

Antibiotics to Use with Caution

• Tetracyclines (e.g., doxycycline)
• Certain quinolones (e.g., ciprofloxacin)
• Metronidazole
• Trimethoprim-sulfamethoxazole
• Certain fluoroquinolones (e.g., moxifloxacin)

Monitoring and Patient Education

• More frequent INR monitoring is advisable, particularly within 3-5 days of starting the antibiotic 1.
• Patients should be educated about signs of excessive anticoagulation, such as unusual bruising, nosebleeds, or blood in urine or stool.

From the FDA Drug Label

The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: EXOGENOUS FACTORS:

• fluoroquinolones
• trimethoprim/sulfamethoxazole
• doxycycline
• norfloxacin
• ofloxacin

Antibiotics that may increase PT/INR response:

• Fluoroquinolones
• Trimethoprim/sulfamethoxazole
• Doxycycline
• Norfloxacin
• Ofloxacin

Note: The FDA drug label does not provide a list of antibiotics that are compatible with warfarin therapy. However, it lists antibiotics that may increase the PT/INR response. Therefore, caution should be exercised when using these antibiotics with warfarin. More frequent PT/INR monitoring is advisable when these medications are started or stopped 2.

From the Research

Antibiotics Compatible with Warfarin

When considering antibiotics for patients on warfarin therapy, it's crucial to choose those that have a lower risk of interaction. The following points summarize compatible antibiotics and those that should be used with caution:

• Low-risk antibiotics:
  • Clindamycin 3
  • Cephalexin 3
• High-risk antibiotics:
  • Trimethoprim/sulfamethoxazole (TMP/SMX) 3, 4
  • Ciprofloxacin 3, 4
  • Levofloxacin 3, 4
  • Metronidazole 3
  • Fluconazole 3
  • Azithromycin 3, 5
  • Clarithromycin 3, 5

Considerations for Antibiotic Use with Warfarin

It's essential to monitor the international normalized ratio (INR) when co-prescribing antibiotics with warfarin, as some antibiotics can increase the risk of bleeding events 3, 4. Early INR evaluation may help mitigate this risk 3. Additionally, factors such as cancer diagnosis, elevated baseline INR, and female sex can predict a higher risk of excessive anticoagulation 4.

General Guidance

While specific antibiotics may have a higher or lower risk of interaction with warfarin, the overall risk of bleeding events should be considered when selecting an antibiotic for a patient on warfarin therapy 6. It's also important to note that acute upper respiratory tract infections can increase the risk of excessive anticoagulation independent of antibiotic use 4.