fluoxetine and warfarin

Fluoxetine inhibits cytochrome P450 2C9, the main enzyme responsible for warfarin metabolism, reducing its clearance and increasing plasma concentrations. Additionally, fluoxetine's serotonin reuptake inhibition impairs platelet aggregation, adding a pharmacodynamic component to the bleeding risk.

Co-prescription can lead to elevated international normalised ratio and an increased risk of serious bleeding, including gastrointestinal and intracranial haemorrhage. The effect may take several days to develop and can persist after fluoxetine is stopped due to its long half-life.

Avoid concurrent use if possible. If combined, monitor the international normalised ratio closely for at least two weeks after starting fluoxetine and after any dose change, and adjust warfarin dose accordingly. Review the patient for signs of bleeding and consider alternative antidepressants with less interaction potential.

Well established in clinical practice and supported by multiple case reports and observational studies. The interaction is listed in major drug interaction compendia.