Major
Established
Description
Naproxen with apixaban significantly increases GI bleeding risk through additive effects on hemostasis and direct gastric mucosal damage.
Mechanism
Naproxen inhibits COX-1–mediated platelet aggregation and damages the gastric mucosa, creating bleeding sites; apixaban prevents effective fibrin clot formation at those sites.
Clinical Significance
Patients on any anticoagulant face 3–15 times higher GI bleed risk when NSAIDs are added; dabigatran and rivaroxaban data are most robust, but extrapolation to apixaban is well-supported.
Management
Avoid; use acetaminophen for analgesia. If NSAID is necessary, use for the shortest possible time with a PPI.