warfarin and naproxen

Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of clotting factors II, VII, IX and X. Naproxen, a nonsteroidal anti-inflammatory drug, inhibits cyclooxygenase, decreasing platelet thromboxane A2 production and impairing platelet aggregation. Naproxen also increases the risk of gastrointestinal ulceration and bleeding. These effects combine to produce a synergistic increase in bleeding tendency.

The combined use of warfarin and naproxen significantly increases the risk of serious haemorrhage, particularly gastrointestinal bleeding. Patients may present with melaena, haematemesis, or other signs of occult blood loss. The INR may also be elevated, although the effect is highly variable and not entirely predictable.

Avoid co-prescription where possible. If the combination is essential, use the shortest possible duration of naproxen, monitor INR at least weekly, and consider adding gastroprotection (e.g., a proton pump inhibitor). Counsel the patient to report any symptoms of bleeding. Alternative analgesics such as paracetamol may be preferred.

The interaction is well established. Numerous observational studies and case reports demonstrate increased bleeding risk with warfarin and NSAIDs. Clinical guidelines recommend caution or avoidance. The mechanism is pharmacodynamic, with a possible pharmacokinetic component due to protein binding displacement, though the latter is of minor clinical importance.