Acetylsalicylic acid × Fluoxetine

Fluoxetine, like other SSRIs, blocks serotonin uptake into platelets, and platelets need serotonin to stop bleeding. Aspirin irreversibly blocks platelet cyclooxygenase and injures the stomach lining. Together they raise the risk of bleeding, above all from the upper gastrointestinal tract (aspirin 100 mg and fluoxetine labels).

Gum bleeding, epistaxis, bruising without trauma, black stools, blood in urine. Severe cases include gastrointestinal or intracranial haemorrhage.

Aspirin SmPCs, including those for 100 mg products, advise avoiding SSRIs with aspirin whenever possible because of bleeding risk, especially gastrointestinal (aspirin 100 mg and 500 mg SmPCs). If the combination is needed, use it with caution (fluoxetine SmPC) and explain the signs of bleeding to the patient in advance: black stools, vomiting blood, abdominal pain, weakness, dizziness, cold sweat. If they appear, the patient stops treatment and seeks medical care at once (aspirin 100 mg SmPC). The FDA also asks prescribers to warn patients about the higher bleeding risk when fluoxetine is combined with aspirin (US fluoxetine label).