warfarin and diclofenac

Pharmacodynamic: additive or synergistic effects on haemostasis. Warfarin inhibits vitamin K-dependent clotting factor synthesis, while diclofenac inhibits platelet aggregation and causes direct gastric mucosal damage, increasing bleeding risk. Pharmacokinetic: both are metabolised by CYP2C9, but diclofenac is not a clinically significant inhibitor of warfarin metabolism.

The combination significantly increases the risk of serious gastrointestinal bleeding, including life-threatening episodes. Patients may develop melaena, haematemesis, or other bleeding manifestations such as epistaxis and increased bruising. The risk is highest in the elderly and those with a history of peptic ulcer disease.

Avoid co-prescription where possible. If the combination is necessary, use the lowest effective dose of diclofenac for the shortest duration and consider gastroprotection with a proton pump inhibitor. Monitor INR closely (e.g., more frequently than usual) and watch for signs of bleeding. Consider alternative analgesics such as paracetamol or opioid-based analgesia.

Well-established through clinical experience and observational studies. The increased bleeding risk with warfarin and NSAIDs is a widely recognised interaction. No specific dose adjustments are defined, but caution is universally advised.