Safety of Taking Cymbalta (Duloxetine) with Plavix (Clopidogrel)
Taking Cymbalta (duloxetine) with Plavix (clopidogrel) is generally safe, but requires monitoring for increased bleeding risk, especially in patients with additional risk factors for bleeding.
Interaction Mechanism and Risk Assessment
Duloxetine and clopidogrel have different mechanisms that may potentially increase bleeding risk when used together:
- Clopidogrel (Plavix): Acts as a P2Y12 inhibitor that irreversibly inhibits platelet aggregation for the lifetime of the platelet (7-10 days) 1
- Duloxetine (Cymbalta): As an SNRI, it inhibits serotonin reuptake which may affect platelet function
Bleeding Risk Factors to Consider
When assessing the safety of this combination, evaluate for these additional risk factors that increase bleeding risk:
- Advanced age
- History of GI bleeding
- Concurrent use of:
- Anticoagulants
- NSAIDs
- Steroids
- Renal dysfunction
- Liver disease
Evidence-Based Recommendations
For most patients: The combination can be used with appropriate monitoring
- No specific contraindication exists in FDA labeling for this combination
- Duloxetine's drug interactions focus primarily on CYP2D6 and CYP1A2 interactions, not direct interactions with clopidogrel 2
For high-risk patients (those with multiple bleeding risk factors):
- Consider adding a proton pump inhibitor (PPI) for GI protection
- While there was historical concern about PPI interaction with clopidogrel, the ACC/AHA consensus document notes that clinical decisions must balance both CV and GI risks 3
- If using a PPI with clopidogrel, pantoprazole may be preferred over omeprazole based on less CYP2C19 inhibition 4
Monitoring recommendations:
- Watch for signs of bleeding (bruising, petechiae, melena, hematemesis)
- Monitor blood counts periodically
- Educate patients about bleeding symptoms to report
Special Considerations
Discontinuation Timing
If the combination must be temporarily discontinued (e.g., for surgery):
- Clopidogrel should be interrupted 5 days prior to surgery with major bleeding risk 1
- Resume as soon as hemostasis is achieved
Concomitant NSAID Use
The risk of bleeding significantly increases if NSAIDs are added to this combination:
- A study showed that concomitant NSAID use with duloxetine was associated with a higher incidence of bleeding-related events compared to duloxetine alone 5
- The same study showed this effect was similar with placebo plus NSAIDs, suggesting the NSAID is the primary driver of increased bleeding risk
Conclusion
While there is a theoretical increased risk of bleeding when combining duloxetine and clopidogrel, this combination is not contraindicated and can be used with appropriate monitoring, especially in patients who require both medications for their respective indications. The benefits of treating both conditions often outweigh the potential risks of the combination.