Erythromycin and Apixaban: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Aug 8, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Erythromycin
Apixaban
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.
Erythromycin is an antibiotic, and apixaban (Eliquis) is a blood thinner that helps prevent clots. When you take them together, the erythromycin can slow down how your body clears the apixaban. That means a little more apixaban can build up in your blood, which can raise your chance of bleeding or bruising more easily.
The good news is this is very manageable. Watch for signs like unusual bruising, nosebleeds, pink or red urine, or black stools, and let your doctor know if they happen. Don't stop either medicine on your own. Your care team can keep you safe by monitoring you or adjusting things if needed.
Effect: Increased apixaban exposure and elevated bleeding risk.
Mechanism: Apixaban is a substrate of both CYP3A4 and P-gp. Erythromycin is a moderate CYP3A4 inhibitor and P-gp inhibitor, so dual inhibition reduces apixaban metabolism and efflux, increasing serum concentrations. Apixaban is active drug (not a prodrug), so inhibition increases anticoagulant effect.
- Magnitude: A comparable dual inhibitor (diltiazem) raised apixaban Cmax ~31% and AUC ~39%.
- Onset: Unspecified.
- Evidence: Probable; severity major.
Management: Use with caution if combined. Monitor for bleeding; dose may need individualization by the care team based on indication, renal function, and other apixaban interactions.
What happens
Increased apixaban exposure and increased risk of bleeding
Interaction Deep Dive
Apixaban is metabolized as a substrate of P-gp as well as CYP3A42, so taking it alongside an agent that inhibits both P-gp and moderately inhibits CYP3A4 can raise apixaban serum levels 5 and heighten the likelihood of bleeding 4. One pharmacokinetic study showed that when apixaban was given together with diltiazem, which acts as a dual P-gp and moderate CYP3A4 inhibitor, its Cmax rose by 31% and its AUC by 39% 5. Should the two need to be used together, exercise caution 31.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of apixaban
How to manage this interaction
Keep taking both as prescribed unless your prescriber tells you otherwise. This combination can be used carefully when needed.
Here is what typically happens and what you can do:
- Your care team may monitor you more closely for signs of bleeding, and your apixaban dose may need to be adjusted and individualized based on your situation.
- Watch for unusual bruising, nosebleeds, bleeding gums, red or dark urine, black stools, or bleeding that won't stop, and report these right away.
- Tell your pharmacist and doctor about all your medicines so they can weigh this interaction against your other risk factors.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a retrospective observational analysis (N=426), the use of a combined P-gp and moderate CYP3A4 inhibitor markedly raised the risk of bleeding among patients receiving apixaban or rivaroxaban for atrial fibrillation. Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, was seen in 26.4% of the group taking an interacting agent compared with 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). The interacting agents were diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); none of the patients were given concurrent erythromycin. When individual drug interactions were assessed, no significant differences in bleeding rates emerged, and the influence of renal dysfunction, the particular inhibitor, or the particular anticoagulant was not assessed 4.
b) Giving diltiazem, a dual P-gp and moderate CYP3A4 inhibitor, together with apixaban raised apixaban Cmax by 31% and AUC by 39% relative to apixaban given alone. Oral apixaban 10 mg was given 8 days after starting diltiazem 360 mg once daily in 18 subjects 5.
Common questions
Can I take Erythromycin and Apixaban together?
Taking erythromycin can raise apixaban levels and increase bleeding risk, so use both together only with your care team's guidance and watch for unusual bleeding or bruising. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Erythromycin and Apixaban interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Erythromycin and Apixaban interaction managed?
Keep taking both as prescribed unless your prescriber tells you otherwise. This combination can be used carefully when needed. Here is what typically happens and what you can do: Your care team may monitor you more closely for signs of bleeding, and your apixaban dose may need to be adjusted and individualized based on your situation. Watch for unusual bruising, nosebleeds, bleeding gums, red or d… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Erythromycin or Apixaban 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)
- Burnett AE, Mahan CE, Vazquez SR, et al: Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis 2016; 41(1):206-232. PubMed
- Product Information: ELIQUIS(R) oral tablets, apixaban oral tablets. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2019. DailyMed
- Steffel J, Collins R, Antz M, et al: 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23(10):1612-1676.
- Hanigan S, Das J, Pogue K, et al: The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding. J Thromb Thrombolysis 2020; 49(4):636-643. PubMed
- Frost CE, Byon W, Song Y, et al: Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015; 79(5):838-846.
Keep reading about Erythromycin
Keep reading about Apixaban
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