Can I prescribe naproxen (Nonsteroidal Anti-Inflammatory Drug) to a patient taking Eliquis (apixaban)?

Naproxen and Eliquis (Apixaban) Combination: Bleeding Risk Considerations

Naproxen should be avoided in patients taking Eliquis (apixaban) due to a significantly increased risk of bleeding, with a more than two-fold higher bleeding rate when NSAIDs are used with oral anticoagulants. 1

Bleeding Risk Assessment

The combination of NSAIDs like naproxen with direct oral anticoagulants (DOACs) such as Eliquis poses substantial bleeding risks:

• Recent evidence shows that patients on oral anticoagulants for venous thromboembolism have a 2.09-fold increased risk of any bleeding when using NSAIDs 1
• Specifically, naproxen carries one of the highest bleeding risks among NSAIDs with a 4.10-fold increased risk compared to non-use when combined with anticoagulants 1
• The ARISTOTLE trial found that incident NSAID use in patients on apixaban was associated with a 61% increased risk of major bleeding (HR 1.61) 2
• Bleeding risk is not limited to gastrointestinal sites but includes intracranial bleeding (HR 3.22) and other sites 1

Gastrointestinal Risk Considerations

NSAIDs combined with anticoagulants significantly increase gastrointestinal bleeding risk:

• Patients taking anticoagulants are considered very high-risk for GI complications when NSAIDs are added 3
• The combination increases the risk of GI bleeding approximately 3-fold 4
• Current guidelines recommend avoiding NSAIDs in anticoagulated patients whenever possible 3

Alternative Approaches

If pain management is necessary for a patient on Eliquis:

1. First-line alternative: Use acetaminophen (paracetamol) instead of NSAIDs for pain relief 4

2. If NSAID is absolutely necessary:

   • Use the lowest effective dose for the shortest duration possible 4
   • Add a proton pump inhibitor (PPI) for gastroprotection 3
   • Consider celecoxib plus PPI instead of naproxen plus PPI (shown to have lower bleeding risk in high-risk patients) 5
   • Monitor closely for signs of bleeding

3. For severe inflammatory conditions requiring anti-inflammatory therapy:

   • Consider short-term corticosteroids instead of NSAIDs 3
   • Consult with the provider managing anticoagulation before prescribing

Special Considerations

• Temporary interruption of anticoagulation is generally not recommended solely to accommodate NSAID use
• For elective procedures requiring NSAIDs, follow appropriate DOAC interruption protocols 3
• The risk of bleeding with this combination appears similar regardless of whether the patient is taking apixaban or warfarin 2
• Even short-term NSAID treatment increases bleeding risk in anticoagulated patients 6

Monitoring Recommendations

If the combination cannot be avoided:

• Educate patients about bleeding warning signs
• Monitor for signs of bleeding at all sites, not just GI tract
• Consider more frequent follow-up during concurrent use
• Be vigilant for both overt bleeding (e.g., hematemesis, melena) and occult bleeding (fatigue, anemia)

The evidence clearly demonstrates that the combination of naproxen and Eliquis significantly increases bleeding risk, and alternative pain management strategies should be strongly considered.