rivaroxaban and diclofenac

Pharmacodynamic interaction: rivaroxaban inhibits factor Xa, reducing thrombin generation and clot formation. Diclofenac, a non-steroidal anti-inflammatory drug, inhibits platelet cyclo-oxygenase-1, reducing thromboxane A2 and platelet aggregation. Additionally, diclofenac can cause gastric mucosal injury by impairing prostaglandin-mediated protective mechanisms. These effects combine to increase the risk of haemorrhage, particularly from the upper gastrointestinal tract.

Co-administration significantly increases the risk of major bleeding, including gastrointestinal haemorrhage, intracranial bleeding, and bleeding from other sites. The risk is further elevated in patients with other predisposing factors such as age over 65 years, prior peptic ulcer disease, or concomitant use of other antiplatelet agents. Clinical outcomes may range from minor bruising to life-threatening haemorrhage.

Avoid concurrent use where possible, especially in patients with high bleeding risk. Consider alternative analgesic or anti-inflammatory therapy, such as paracetamol or a selective cyclo-oxygenase-2 inhibitor, after assessing cardiovascular risk. If co-administration is unavoidable, prescribe the lowest effective dose and shortest duration of diclofenac, and monitor closely for signs of bleeding (e.g., melaena, haematemesis, fall in haemoglobin). Consider gastroprotective therapy with a proton pump inhibitor.

Well-established interaction based on pharmacodynamic principles and multiple cohort and case-control studies showing increased bleeding risk with combined anticoagulant and NSAID therapy. Guidelines and prescribing information recommend caution or avoidance.