What is the interaction between azithromycin (Zithromax, Z-pack) and warfarin?

From the Guidelines

Azithromycin (Z-pack) and warfarin can interact, potentially increasing the risk of bleeding, and patients taking warfarin who are prescribed azithromycin should continue both medications but require closer monitoring of their INR levels during and shortly after the antibiotic course. This interaction is due to azithromycin's ability to alter the gut microbiome, which is a rich source of vitamin K, and thereby potentiate anticoagulant effects of warfarin 1. Additionally, azithromycin may also inhibit certain liver enzymes involved in warfarin breakdown, such as CYP3A4, which can further exacerbate this interaction 1.

Key Considerations

• Patients taking warfarin who are prescribed azithromycin should contact their healthcare provider before starting the Z-pack to discuss whether more frequent INR testing is needed.
• The interaction between azithromycin and warfarin can increase the risk of adverse bleeding, and patients should watch for signs of increased bleeding such as unusual bruising, nosebleeds, bleeding gums, or blood in urine or stool 1.
• If signs of increased bleeding occur, patients should seek medical attention immediately.
• Most patients can safely take both medications with appropriate monitoring, and the antibiotic course should not be skipped if it's medically necessary.

Monitoring and Management

• Patients taking warfarin and azithromycin should have their INR levels closely monitored during and shortly after the antibiotic course.
• Pre-emptive warfarin dose reductions may not be necessary for azithromycin, but this should be determined on a case-by-case basis, taking into account the individual patient's risk factors and medical history 1.
• Healthcare providers should be aware of the potential interaction between azithromycin and warfarin and take steps to minimize the risk of adverse bleeding.

From the FDA Drug Label

Although, in a study of 22 healthy men, a 5-day course of azithromycin did not affect the prothrombin time from a subsequently administered dose of warfarin, spontaneous post-marketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.

• Key Points:
  • Azithromycin may potentiate the effects of oral anticoagulants like warfarin.
  • Prothrombin times should be carefully monitored when azithromycin and warfarin are used concomitantly.
• Clinical Decision: When prescribing azithromycin to patients on warfarin, close monitoring of prothrombin times is recommended to minimize the risk of bleeding complications 2.

From the Research

Interaction between Zpack (Azithromycin) and Warfarin

• The interaction between azithromycin and warfarin has been studied in several research papers 3, 4, 5, 6, 7.
• A study published in 2013 found that the addition of azithromycin to a stable warfarin regimen resulted in a significant change in the international normalized ratio (INR) and warfarin dosage alteration without an increase in bleeding 3.
• Another study published in 2004 reported a case of a patient who experienced an increase in INR after taking azithromycin while on warfarin, highlighting the potential for interaction between the two drugs 4.
• However, a retrospective review of 52 patients published in 2000 found no significant interaction between azithromycin and warfarin in patients with a stable INR 5.
• A study published in 2014 found that the use of high-risk antibiotics, including azithromycin, was associated with an increased risk of serious bleeding events in patients taking warfarin 6.
• Another study published in 2014 found that acute upper respiratory tract infection increased the risk of excessive anticoagulation independent of antibiotic use, and that antibiotics also increased the risk, but most patients with previously stable warfarin therapy did not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection 7.

Key Findings

• Azithromycin can interact with warfarin, leading to changes in INR and warfarin dosage 3, 4.
• The risk of bleeding events is increased when azithromycin is co-prescribed with warfarin 6.
• Regular monitoring of INR values is recommended when azithromycin is prescribed to patients taking warfarin 4, 6.
• The interaction between azithromycin and warfarin can be significant, but the risk of serious bleeding events is relatively low 6, 7.