warfarin and ibuprofen

Warfarin inhibits vitamin K-dependent clotting factors. Ibuprofen has a dual effect: it inhibits platelet aggregation and damages the gastric mucosa, increasing bleeding risk. Additionally, ibuprofen competes with warfarin for plasma protein binding and inhibits the CYP2C9 enzyme, which can raise warfarin plasma concentrations and prolong INR.

Co-prescription markedly increases the risk of major bleeding, particularly gastrointestinal haemorrhage. Patients may present with melaena, haematemesis, or intracranial bleeding. The INR may rise unpredictably, and the antiplatelet effect of ibuprofen persists even after the drug is cleared.

Avoid concurrent use if possible. Prefer paracetamol or a short course of a proton pump inhibitor plus a less gastrotoxic NSAID if an NSAID is essential. If no alternative exists, use the lowest effective dose of ibuprofen for the shortest duration, monitor INR within 3 to 5 days of initiation and regularly thereafter, and watch for signs of bleeding. Prescribe gastroprotection with a proton pump inhibitor.

Well established in clinical practice and supported by observational studies and case series. The interaction is widely recognised in drug interaction compendia. However, the magnitude of INR elevation is variable and may be modest in some patients, while the bleeding risk is consistently increased.