From the FDA Drug Label
Concomitant administration of warfarin (2 to 9 mg once daily) under steady state conditions with duloxetine delayed-release capsules 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0. 07). The total warfarin (protein bound plus free drug) pharmacokinetics (AUC τ,ss, C max,ss or t max,ss) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine delayed-release capsules are initiated or discontinued [see WARNINGS AND PRECAUTIONS (5. 5)] .
The interaction between duloxetine (Cymbalta) and warfarin is as follows:
- No significant change in INR: Co-administration of warfarin with duloxetine did not significantly change INR from baseline.
- No alteration in warfarin pharmacokinetics: The total warfarin pharmacokinetics were not altered by duloxetine.
- Monitoring recommended: Patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued due to the potential effect of duloxetine on platelets 1.
From the Research
Duloxetine (Cymbalta) can be used with warfarin without significant interactions, as evidenced by a study showing no clinically or statistically significant effect on the pharmacodynamics or pharmacokinetics of warfarin at steady state 2. When considering the use of duloxetine with warfarin, it is essential to prioritize the patient's morbidity, mortality, and quality of life. The primary concern with concomitant use of these medications is the potential for increased bleeding risk due to warfarin's anticoagulant effects. However, the study by 2 found that duloxetine had no significant impact on warfarin's pharmacodynamics or pharmacokinetics, suggesting that the risk of bleeding may not be substantially increased.
Key points to consider when using duloxetine with warfarin include:
- Monitoring INR levels regularly, especially when starting, stopping, or changing the dose of either medication
- Informing all healthcare providers about all medications being taken, including over-the-counter drugs and supplements
- Watching for signs of increased bleeding, such as unusual bruising, nosebleeds, or prolonged bleeding from cuts
- Not adjusting either medication without consulting a healthcare provider
- Seeking medical attention promptly if side effects occur, rather than discontinuing medications independently
It is also important to note that while the study by 2 found no significant interaction between duloxetine and warfarin, other studies have reported interactions between warfarin and other medications, such as SSRIs 3 and azathioprine 4. However, these interactions may not be directly applicable to the use of duloxetine with warfarin. A more recent study 5 found that some medications, such as miconazole and amiodarone, can have a significant impact on INR levels, but duloxetine was not specifically studied. Therefore, the combination of duloxetine and warfarin can be used, but with careful monitoring and consideration of the patient's individual risk factors.