Edoxaban ( Lixiana, Savaysa ) is an oral factor Xa ( FXa ) inhibitor in clinical development for stroke prevention in patients with atrial fibrillation, an elderly population that frequently receives Aspirin ( ASA; Acetylsalicylic acid ) and/or nonsteroidal anti-inflammatory drugs ( NSAIDs ) ( for concurrent illnesses.
Three studies were conducted to evaluate the pharmacokinetic and pharmacodynamic interactions of Edoxaban 60 mg coadministered with low-dose ( 100 mg ) Aspirin, high-dose ( 325 mg ) Aspirin, or Naproxen ( 500 mg ) in healthy subjects ( n=126 ).
Template bleeding times ( BT ) were measured. Mean baseline ( predose ) BT for the 3 studies ranged from 4.72 to 6.13 minutes.
Edoxaban administered alone increased BT by 21-35% ( 4 hours post dose ) from baseline. Concomitant administration of Edoxaban with high-dose Aspirin, low-dose Aspirin, or Baproxen increased BT approximately 2-fold showing an additive effect greater than either agent administered alone.
Edoxaban pharmacokinetics were not affected by concomitant low-dose Aspirin or Naproxen, but high-dose Aspirin increased systemic exposure of Edoxaban by approximately 30%.
The effects of Edoxaban on prothrombin time, activated partial thromboplastin time, international normalized ratio, anti-FXa, and intrinsic FXa activity were not influenced by administration with Aspirin or Naproxen.
Inhibition of platelet aggregation by high-dose Aspirin, low-dose Aspirin, or Naproxen was not affected by Edoxaban. Concomitant administration of Edoxaban and Aspirin or Naproxen was well tolerated. ( Xagena )
Mendell J et al, J Cardiovasc Pharmacol 2013;62:212-221