What is the interaction between Eliquis (apixaban) and diclofenac?

From the Guidelines

Eliquis (apixaban) and diclofenac can be taken together, but this combination increases bleeding risk and should be used with caution. According to the most recent guidelines, specifically the 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation 1, the use of apixaban, a Factor Xa inhibitor, requires careful consideration of potential drug interactions, including those with nonsteroidal anti-inflammatory drugs (NSAIDs) like diclofenac.

When taking Eliquis and diclofenac together, it's essential to be aware of the increased risk of bleeding, particularly in the digestive tract. Diclofenac, as an NSAID, can affect platelet function and irritate the stomach lining, while Eliquis works as a blood thinner by inhibiting Factor Xa in the clotting cascade. This dual effect on blood clotting heightens the risk of bleeding complications.

To manage this risk, patients should:

• Inform all healthcare providers about the combination of Eliquis and diclofenac.
• Watch for signs of bleeding, such as unusual bruising, black stools, or blood in urine.
• Consider taking diclofenac with food to reduce stomach irritation.
• Avoid other blood-thinning medications or supplements like aspirin or high-dose vitamin E without medical approval.
• Undergo regular monitoring by their healthcare provider to adjust the treatment plan as necessary and minimize the risk of adverse effects.

Given the potential for increased bleeding risk, the decision to use Eliquis and diclofenac together should be made with caution and under the guidance of a healthcare provider, taking into account the individual patient's risk factors and medical history, as suggested by studies on the management of patients with atrial fibrillation and those requiring anticoagulation therapy 1.

From the FDA Drug Label

1. 3 Anticoagulants and Antiplatelet Agents Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding

Table 2. Clinically Significant Drug Interactions with Diclofenac Drugs That Interfere with Hemostasis Clinical Impact: Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.

The concomitant use of apixaban (Eliquis) and diclofenac may increase the risk of bleeding.

• Key points:
  • Concomitant use of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding.
  • Diclofenac and anticoagulants have a synergistic effect on bleeding.
• Clinical decision: Monitor patients for signs of bleeding when using apixaban and diclofenac concomitantly 2 3.

From the Research

Eliquis and Diclofenac Interaction

• The interaction between Eliquis (apixaban) and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), has been studied in the context of patients with atrial fibrillation 4.
• The use of NSAIDs with oral anticoagulants, such as apixaban, has been associated with an increased risk of bleeding 4.
• A study found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding 4.
• Another study found that proton pump inhibitor (PPI) co-therapy was associated with a significant reduction in the risk of major gastrointestinal bleeding in patients treated with rivaroxaban and warfarin, but not in those treated with apixaban 5.
• The concomitant use of several systemic NSAIDs, including diclofenac, has been associated with an excess risk of adverse effects such as hepatic injury, acute renal failure, and gastrointestinal bleeding 6.

Bleeding Risk

• The risk of bleeding associated with the use of NSAIDs and oral anticoagulants, such as apixaban, is a significant concern 4, 5.
• Patients with a history of bleeding are more likely to experience bleeding events when taking NSAIDs and oral anticoagulants 4.
• The use of PPIs as co-therapy with oral anticoagulants may help reduce the risk of gastrointestinal bleeding, but the effectiveness of this strategy may vary depending on the specific oral anticoagulant used 5.

Polypharmacy and Drug Interactions

• Polypharmacy, defined as the concurrent use of five or more drugs, can increase the risk of adverse drug events, clinically relevant drug interactions, and all-cause mortality 7.
• The concomitant use of multiple NSAIDs, including diclofenac, can increase the risk of adverse effects such as hepatic injury, acute renal failure, and gastrointestinal bleeding 6.
• Collaboration with pharmacists and the use of tools such as the Medication Appropriateness Index (MAI) and the American Geriatrics Society (AGS) Beers Criteria can help identify and mitigate potential drug interactions and adverse effects 7.