Major
sertraline × warfarin
Selective serotonin reuptake inhibitors (SSRIs)×Vitamin K antagonist anticoagulants
Mechanism
Dual mechanism: 1) sertraline inhibits serotonin reuptake in platelets, depleting platelet serotonin and reducing aggregation; 2) moderate CYP2C9 inhibition raises warfarin concentration and INR. GI bleeding risk roughly doubles.
Management
When starting sertraline in a warfarin-treated patient, check INR at 1, 2, and 4 weeks. Add a PPI (pantoprazole) if GI bleeding risk factors are present. Alternatives include mirtazapine (less serotonergic activity) or agomelatine.
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)— Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)— Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024