Major
Established
Deskripsi
Ibuprofen combined with warfarin substantially increases bleeding risk, particularly gastrointestinal hemorrhage, through complementary antiplatelet and mucosal injury mechanisms.
Mekanisme
Ibuprofen reversibly inhibits COX-1 and COX-2, impairing platelet function and causing gastric mucosal damage; high-dose ibuprofen can also inhibit CYP2C9, increasing warfarin plasma levels.
Signifikansi Klinis
The combination is associated with a 3- to 15-fold increased risk of upper GI hemorrhage compared with warfarin alone.
Penatalaksanaan
Avoid concurrent use; substitute acetaminophen (≤2 g/day) for mild-to-moderate pain. If NSAID is essential, add a PPI and increase INR monitoring frequency.