apixaban and naproxen

Pharmacodynamic interaction: both drugs impair haemostasis. Apixaban inhibits factor Xa, reducing thrombin generation. Naproxen inhibits cyclooxygenase, reducing thromboxane A2 and impairing platelet aggregation. Naproxen also causes direct gastrointestinal mucosal injury, increasing bleeding risk from erosions and ulcers.

Co-administration significantly increases the risk of major bleeding, particularly gastrointestinal haemorrhage, intracranial bleeding, and other serious bleeding events. Patients may present with melaena, haematemesis, or falls in haemoglobin. The risk is higher in older patients, those with prior peptic ulcer disease, or those on other antiplatelet agents.

Avoid concomitant use unless strongly indicated. If co-prescription is necessary, use the lowest effective dose of naproxen for the shortest duration, consider gastroprotective therapy (e.g., a proton pump inhibitor), and monitor closely for signs of bleeding. Advise the patient to report any unusual bruising, black stools, or blood in vomit. Periodic full blood counts and stool occult blood testing may be considered.

Well-established from multiple randomised controlled trials and meta-analyses showing increased bleeding risk with combined anticoagulants and NSAIDs, based on pharmacodynamic principles and clinical outcome data.