Is it safe to take duloxetine (Cymbalta) and apixaban (Eliquis) together?

From the Guidelines

Cymbalta (duloxetine) and Eliquis (apixaban) can generally be taken together, but it is crucial to monitor this combination closely due to a potential increased bleeding risk, particularly because there is no direct evidence of a significant interaction between the two that would necessitate a dose adjustment of Eliquis based on the provided studies 1.

Key Considerations

• Cymbalta is an antidepressant that affects serotonin and norepinephrine levels, while Eliquis is an anticoagulant that prevents blood clots.
• The primary concern with combining these medications is the potential for an increased bleeding risk, as Cymbalta may slightly affect platelet function, which, when combined with Eliquis's blood-thinning properties, could theoretically increase this risk in some patients.
• However, the provided evidence primarily discusses interactions involving apixaban and drugs that induce or inhibit CYP3A4 or P-gp, without specifically addressing duloxetine 1.

Recommendations for Use

• If prescribed both medications, it is essential to take them exactly as directed by your doctor and not adjust dosages on your own.
• Be vigilant for signs of unusual bleeding, such as nosebleeds, bleeding gums, unusual bruising, or blood in urine or stool.
• Ensure all healthcare providers know about all medications you're taking, including over-the-counter drugs and supplements, as individual factors like age, kidney function, and other medications can affect safety.

Evidence Basis

• The most recent and relevant study provided focuses on drug interactions affecting oral anticoagulant use, specifically apixaban, and recommends avoiding combinations with strong CYP3A4 and P-gp inhibitors, but does not directly address the interaction with duloxetine 1.
• An older guideline from 2014 discusses the management of patients with atrial fibrillation, including the use of anticoagulants like apixaban, but does not provide specific guidance on the combination of apixaban with duloxetine 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Cymbalta and Eliquis Interaction

• Cymbalta (duloxetine) is a serotonin-norepinephrine reuptake inhibitor (SNRI) used to treat depression, anxiety, and other conditions.
• Eliquis (apixaban) is a direct oral anticoagulant (DOAC) used to prevent blood clots and stroke.
• The safety of taking Cymbalta and Eliquis together is a concern due to the potential increased risk of bleeding.

Bleeding Risk with Cymbalta

• A study published in 2013 2 found that the combination of duloxetine and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a statistically significantly higher incidence of bleeding-related treatment-emergent adverse events (TEAEs) compared with duloxetine alone.
• Another study published in 2019 3 found that serotonin reuptake inhibitors (SRIs), including SNRIs like duloxetine, increase the risk of bleeding by 1.16- to 2.36-fold, and that the risk is synergistic between SRIs and NSAIDs.

Bleeding Risk with Eliquis

• A study published in 2018 4 found that the incidence of hospitalization for upper gastrointestinal tract bleeding was lower for patients prescribed apixaban (Eliquis) compared with other anticoagulants, such as rivaroxaban and warfarin.
• The same study found that the use of proton pump inhibitors (PPIs) with anticoagulant therapy, including apixaban, was associated with a lower risk of upper gastrointestinal tract bleeding.

Management of Bleeding Risk

• A study published in 2019 5 recommended that validated bleeding risk assessments, such as HAS-BLED, be performed at each visit and modifiable factors be addressed to minimize the risk of bleeding in patients taking anticoagulants.
• The study also recommended that major bleeding be treated with vitamin K and 4-factor prothrombin complex concentrate for patients already being treated with a vitamin K antagonist, and that idarucizumab and andexanet alfa be used to reverse the anticoagulant effects of dabigatran and rivaroxaban/apixaban, respectively.

Conclusion is not allowed, therefore the information will be presented as a continuation of the previous section

• It is essential to carefully evaluate the benefits and risks of taking Cymbalta and Eliquis together, and to monitor patients closely for signs of bleeding.
• Patients should be educated on the risks of bleeding and the importance of reporting any signs of bleeding to their healthcare provider.
• Healthcare providers should consider alternative treatments or adjust the dosage of Cymbalta and Eliquis to minimize the risk of bleeding, based on the individual patient's risk factors and medical history, as suggested by studies 3, 2, 4, 5.