fluoxetine and ibuprofen

Fluoxetine inhibits serotonin reuptake, reducing platelet serotonin content and impairing platelet aggregation. Ibuprofen, an NSAID, inhibits cyclooxygenase, decreasing thromboxane A2 production, which also impairs platelet function. Additionally, NSAIDs disrupt gastric mucosal integrity. Combined pharmacodynamic effects result in additive impairment of haemostasis and increased risk of gastrointestinal bleeding.

The risk of upper gastrointestinal bleeding is increased when these drugs are used together. The effect is greater in patients with existing risk factors such as older age, history of peptic ulcer disease, concurrent anticoagulant or corticosteroid use, or high-dose NSAID therapy. Clinical presentation may include melaena, haematemesis, or unexplained anaemia.

Avoid co-prescription when possible, especially in high-risk patients. If concurrent use is necessary, use the lowest effective dose of ibuprofen for the shortest duration, and consider gastroprotection with a proton pump inhibitor. Monitor patients for signs of GI bleeding, such as black stools, blood in vomit, or dizziness. Advise patients to report any unusual bleeding or abdominal pain.

The interaction is well established through pharmacological principles and observational studies showing increased GI bleeding risk with SSRIs and NSAIDs.