Moderate
Probable
Description
Fluoxetine increases warfarin plasma levels via CYP2C9 inhibition and may independently impair platelet function, raising hemorrhagic risk.
Mechanism
Fluoxetine and its active metabolite norfluoxetine inhibit CYP2C9, reducing S-warfarin clearance; SSRI-mediated platelet serotonin depletion further impairs hemostasis.
Clinical Significance
Case series document significant INR elevations and bleeding events (GI hemorrhage, bruising) when fluoxetine is added to stable warfarin regimens.
Management
Monitor INR within 1–2 weeks of starting or stopping fluoxetine; the long half-life of norfluoxetine means effects persist for weeks after fluoxetine discontinuation.