What are the interactions between naproxen and Eliquis (apixaban)?

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Last updated: April 16, 2025View editorial policy

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From the FDA Drug Label

Pharmacodynamic drug interaction studies with aspirin, clopidogrel, aspirin and clopidogrel, prasugrel, enoxaparin, and naproxen were conducted. No pharmacodynamic interactions were observed with aspirin, clopidogrel, or prasugrel [see Warnings and Precautions (5. 2)]. A 50% to 60% increase in anti-FXa activity was observed when apixaban was coadministered with enoxaparin or naproxen.

The use of naproxen with apixaban (Eliquis) may increase the risk of bleeding due to a 50% to 60% increase in anti-FXa activity. Caution should be exercised when coadministering these medications.

  • Key considerations:
    • Increased risk of bleeding
    • Monitor patient for signs of bleeding
    • Adjust treatment as necessary to minimize risk 1
  • Clinical decision: Use with caution and monitor patient closely for signs of bleeding. 1

From the Research

Taking naproxen while on Eliquis (apixaban) is generally not recommended due to increased bleeding risk, as evidenced by a study published in 2020 2, which found that incident NSAID use was associated with an increased risk of major bleeding and clinically relevant nonmajor bleeding. If you must take both medications, do so only under close medical supervision. Eliquis is a blood thinner that prevents clots, while naproxen is an NSAID that also affects blood clotting. When combined, they can significantly increase your risk of bleeding, including potentially dangerous internal bleeding. Some key points to consider:

  • A study published in 2014 3 found that co-administration of naproxen with apixaban results in higher apixaban exposure, which can increase the risk of bleeding.
  • Another study published in 2018 4 found that the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving proton pump inhibitor (PPI) cotherapy, which may be a consideration for patients taking naproxen and Eliquis.
  • If you need pain relief while on Eliquis, acetaminophen (Tylenol) is typically a safer alternative.
  • For any pain management needs while taking Eliquis, consult your healthcare provider first, as they may recommend specific dosing limitations, shorter duration of use, or alternative pain management strategies based on your individual bleeding risk factors.
  • Never start or stop either medication without medical guidance, as this could affect your treatment for the underlying condition requiring Eliquis.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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