MajorAntiplatelet agents – P2Y12 receptor inhibitors×Selective serotonin reuptake inhibitors
Updated · Methodology
Mechanism
Fluoxetine inhibits CYP2C19, the enzyme converting clopidogrel into its active metabolite. Active levels fall and antiplatelet effect weakens. Fluoxetine also depletes the platelet serotonin pool, impairing primary haemostasis.
Symptoms
Dual risk: weakened antiplatelet effect (raising thrombosis risk) alongside increased upper GI bleeding risk.
Management
Alternative antidepressants: sertraline or escitalopram (weaker CYP2C19 inhibitors), or mirtazapine/agomelatine (minimal platelet effect). Alternative antiplatelet: ticagrelor (not CYP2C19-dependent). PPI cover with pantoprazole is mandatory.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- PubMed: SSRIs increase bleeding risk when combined with antiplatelets and anticoagulants (2019)
- AEMPS: Ficha técnica: Clopidogrel (nº registro 71676), sección 4.5 (2024)– AEMPS, CIMA, nº registro 71676, revisión 02/2024, sección 4.5