Moderate
Probable
Deskripsi
Fluoxetine increases warfarin plasma levels via CYP2C9 inhibition and may independently impair platelet function, raising hemorrhagic risk.
Mekanisme
Fluoxetine and its active metabolite norfluoxetine inhibit CYP2C9, reducing S-warfarin clearance; SSRI-mediated platelet serotonin depletion further impairs hemostasis.
Signifikansi Klinis
Case series document significant INR elevations and bleeding events (GI hemorrhage, bruising) when fluoxetine is added to stable warfarin regimens.
Penatalaksanaan
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.