From the Guidelines
Both fluoxetine and tadalafil can interact with Coumadin (warfarin), but they are not absolutely contraindicated, however caution is warranted when using these medications together, as noted in a study on drug interactions affecting oral anticoagulant use 1.
Key Considerations
- Fluoxetine can inhibit the metabolism of warfarin through the CYP2C9 enzyme system, potentially increasing warfarin's anticoagulant effect and raising the risk of bleeding.
- Tadalafil has a milder interaction with warfarin but may still slightly increase bleeding risk.
- When these medications must be used together, healthcare providers should monitor the patient's INR more frequently, especially during the first few weeks of combined therapy, and adjust the warfarin dose as needed, as suggested by guidelines for managing patients with atrial fibrillation or atrial flutter 1.
Monitoring and Patient Education
- Patients should be educated about signs of excessive anticoagulation such as unusual bruising, nosebleeds, bleeding gums, or blood in urine or stool, and instructed to seek immediate medical attention if these occur.
- The importance of regular INR monitoring cannot be overstated, especially in the context of initiating, stopping, or changing the dose of fluoxetine or tadalafil, as emphasized in the management of patients with unstable angina/non-ST-elevation myocardial infarction 1.
Clinical Decision Making
- The decision to use fluoxetine or tadalafil with Coumadin should be made on a case-by-case basis, considering the individual patient's risk factors for bleeding and thromboembolism, as well as their overall health status and any potential drug interactions, in line with recommendations for the diagnosis and management of atrial fibrillation 1.
From the FDA Drug Label
Because fluoxetine is tightly bound to plasma protein, the administration of fluoxetine to a patient taking another drug that is tightly bound to protein (e.g., Coumadin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued.
- Fluoxetine is not contraindicated with Coumadin, but caution is advised due to potential increased risk of bleeding.
- Tadalafil had no significant effect on exposure (AUC) to S-warfarin or R-warfarin, nor did tadalafil affect changes in prothrombin time induced by warfarin, no contraindication is noted. 2 3
From the Research
Drug Interactions with Coumadin
- The interaction between fluoxetine and Coumadin (warfarin) has been studied, and results suggest that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), may increase warfarin plasma concentrations and the risk of bleeding due to its potent CYP2C9 inhibition 4.
- However, a study found that patients concomitantly treated with warfarin and SSRIs that are potent CYP2C9 inhibitors, such as fluoxetine, had comparable rates of bleeding events, ischemic or thromboembolic events, and mortality as did patients cotreated with warfarin and other SSRIs 4.
- Regarding tadalafil, there is no direct evidence of a contraindication with Coumadin in the provided studies.
- Tadalafil is a phosphodiesterase-5 (PDE5) inhibitor, and its interactions with other medications, such as alpha-blockers and nitrates, have been studied 5, 6, 7, 8.
- However, the provided studies do not specifically address the interaction between tadalafil and Coumadin.