Major
Established
Descripción
Naproxen combined with warfarin increases the risk of GI and other hemorrhagic complications through additive effects on hemostasis and direct gastric mucosal damage.
Mecanismo
Naproxen inhibits COX-1–mediated platelet aggregation and damages gastric mucosa, compounding warfarin's anticoagulant effect and creating a site for bleeding.
Relevancia clínica
Significant increase in upper GI bleeding risk; the interaction is pharmacodynamic and does not require INR to be supratherapeutic for bleeding to occur.
Manejo clínico
Avoid if possible; use acetaminophen instead. If required, add a PPI, use the lowest effective naproxen dose for the shortest duration, and monitor for signs of bleeding.