Drug Interactions between antithrombin (recombinant) and edoxaban

MONITOR CLOSELY: Concomitant use of edoxaban with other agents that alter hemostasis such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, other anticoagulants, thrombolytic agents, or drugs that cause thrombocytopenia may increase the risk of bleeding. In clinical studies of edoxaban, concurrent use of low-dose aspirin (<=100 mg/day), thienopyridines, or NSAIDs was associated with increased rates of clinically relevant bleeding. Coadministration of edoxaban with aspirin (100 mg or 325 mg) or naproxen (500 mg) has been shown to increase bleeding time compared to either drug alone. In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during edoxaban therapy may also be increased by the concomitant use of other drugs that affect coagulation. The development of epidural and spinal hematoma can lead to long-term neurological injury or permanent paralysis.

MANAGEMENT: Caution is recommended if edoxaban must be used with other agents that alter hemostasis. Patients should be monitored for increased anticoagulant effects and bleeding complications. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with caution and only after thorough assessment of risks and benefits. Besides bleeding complications, patients should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.