Warfarin and Azithromycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Warfarin
Azithromycin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of bleeding
Interaction Deep Dive
The concomitant use of azithromycin with warfarin may result in increased INR and thereby increase the risk for bleeding3. In a nested case-control study and a retrospective cohort study, there was a 48% to 2-fold increase in risk of bleeding requiring hospitalization with exposure to any antibiotic therapy. The suggested mechanism of interaction is alteration in intestinal flora that synthesize vitamin K. When possible, substitute azithromycin with an antibiotic with a low-risk profile for bleeding, such as clindamycin and cephalexin 23. If concomitant use is deemed necessary, early and more frequent monitoring of INR is recommended 24, especially during initiation and discontinuation of the antibiotic 5.
Why it happens (mechanism)
Disruption of vitamin K synthesis
Literature reports
4 reports — tap to read
a) In a retrospective study of veterans (N=22,272), coadministration of warfarin and high-risk antibiotics (those with known interaction with warfarin resulting in increased bleeding risk) significantly increased the risk of hospital admission due to serious bleeding by 48% compared with low-risk antibiotics. In the high-risk antibiotics group, azithromycin significantly increased the risk of bleeding by 93% where as other antibiotics had nonsignificant increases individually (fluconazole had an increased risk of 111%, sulfamethoxazole/trimethoprim 79%, clarithromycin 71%, metronidazole 63%, ciprofloxacin 42%, and levofloxacin 30%) compared with low-risk antibiotics clindamycin and cephalexin. INR monitoring within 3 to 14 days of antibiotic therapy reduced the risk of serious bleeding 2.
b) Initiation of antibiotics in patients on continuous warfarin therapy resulted in a significantly increased risk of serious bleeding requiring hospitalization according to a nested case-control study of United States Medicare part D beneficiaries aged 65 and older (n=38,762). Patients on warfarin who received any antibiotic were twice as likely to be hospitalized for bleeding compared with matched controls on warfarin who were not exposed to antibiotics (adjusted odds ratio (aOR), 2.01; 95% CI, 1.62 to 2.5). Additionally, continuous-warfarin users were twice as likely to have a bleeding event that required hospitalization within 60 days of antibiotic exposure compared with non-exposure. Antibiotic exposure greater than 60 days from the index bleed was not significantly associated with an increased risk of bleeding. Specific antibiotics with the highest bleeding risk were azole antifungals (aOR, 4.57; 95% CI, 1.9 to 11.03), followed by cotrimoxazole (aOR, 2.7; 95% CI, 1.46 to 5.05), cephalosporins (aOR, 2.45; 95% CI, 1.52 to 3.95), penicillins (aOR, 1.92; 95% CI, 1.21 to 2.07), macrolides (aOR, 1.86; 95% CI, 1.08 to 3.21), and quinolones (aOR, 1.69; 95% CI, 1.09 to 2.62) 3.
c) Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin 1.
d) In a retrospective review including 100 patients aged 65 years and older who received azithromycin while on stable warfarin therapy, INR was reported to increase significantly. The inclusion criteria consisted of a stable warfarin dose (2 INR values within 0.2 of the therapeutic range and the last INR determined 30 days of less before the introduction of azithromycin) and no medication changes in the 30 days before azithromycin therapy initiation. A repeated INR was determined 3 to 30 days after azithromycin therapy was initiated. Patients were excluded if they discontinued warfarin use, had a history of hemorrhage, or were taking antiplatelets, anti-inflammatory agents, or any other antibiotics during the 30 days before and after initiation of azithromycin. The mean duration of therapy with azithromycin was 4.86 days (range, 1 to 7 days). There was a significant change in the INR before and after azithromycin exposure with a decrease in warfarin from a mean weekly dose of 30 mg to 29.2 mg. However, changes in the INR did not result in vitamin K administration or adverse bleeding events. Closer monitoring when stabilized patients taking warfarin are prescribed azithromycin may be justified during therapy and 6 to 30 days after stopping azithromycin use 4.
Common questions
Can I take Warfarin and Azithromycin together?
An increased risk of bleeding Always confirm with your pharmacist or prescriber before making any change.
How serious is the Warfarin and Azithromycin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
- Are Blueberries Safe To Eat If You Take Warfarin?
- Does Ashwagandha Interact With Warfarin?
- Does Flaxseed Interact With Warfarin?
- Taking Tylenol With Azithromycin For A Sinus Infection
- Discussing The Interaction Between Azithromycin And Hydroxychloroquine
- Can You Take Hawthorn Supplements With Azithromycin (Z-PACK)?
Questions for your pharmacist
- Does my dose of Warfarin or Azithromycin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: ZMAX(R) oral extended-release suspension, azithromycin oral extended-release suspension. Pfizer Inc (per FDA), New York, NY, 2021. DailyMed
- Lane MA, Zeringue A, & McDonald JR: Serious bleeding events due to warfarin and antibiotic co-prescription in a cohort of veterans. Am J Med 2014; 127(7):657-663.e2. PubMed
- Baillargeon J, Holmes HM, Lin YL, et al: Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med 2012; 125(2):183-189. DOI
- Mergenhagen KA, Olbrych PM, Mattappallil A, et al: Effect of azithromycin on anticoagulation-related outcomes in geriatric patients receiving warfarin. Clin Ther 2013; 35(4):425-430. PubMed
- Product Information: WARFARIN SODIUM oral tablets, warfarin sodium oral tablets. Teva Pharmaceuticals (per Dailymed), Parsippany, NJ, 2023. DailyMed
Keep reading about Warfarin
Keep reading about Azithromycin
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