as warfarin in preventing non-hemorrhagic stroke in people with atrial fibrillation and are associated with lower risk of intracranial bleeding. While apixaban may be used in people with severely decreased kidney function and those on hemodialysis it has not been studied in these groups. Side effects Bleeding Apixaban can increase the risk of bleeding which may be serious and potentially fatal. Concurrent use with other medications that affect blood clotting can further increase this risk. This includes medications such as other anticoagulants, heparin, aspirin, antiplatelet medications, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs). Andexanet alfa is a US Food and Drug Administration (FDA) approved antidote for apixaban in people with uncontrolled and life-threatening bleeding events. Spinal puncture Following spinal anesthesia or puncture, people who are being treated with anti-thrombotic agents are at higher risk for developing a hematoma, which causes long-term or permanent paralysis. The risk of this may be increased by using epidural or intrathecal catheters after a surgical operation or from the concurrent use of medicinal agents that affect hemostasis. Mechanism of action Apixaban is a highly selective, orally bioavailable, and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation. Apixaban has no direct effect on platelet aggregation, but by inhibiting factor Xa, it indirectly decreases clot formation induced by thrombin. History Apixaban was approved for medical use in the European Union in May 2011. A new drug application (NDA) for the approval of apixaban was submitted to the U.S. Food and Drug Administration (FDA) by Bristol-Myers Squibb (BMS) and Pfizer jointly after conclusion of the ARISTOTLE clinical trial in 2011. Apixaban was approved for the prevention of stroke in people with atrial fibrillation on 28 December 2012. On 13 March 2014, it was approved for the additional indication of preventing deep vein thrombosis and pulmonary embolism in people who have recently undergone knee or hip replacement. On 21 August 2014, the FDA approved apixaban for the additional indication of the treatment of recurring deep vein thrombosis and pulmonary embolism. During its development the drug was known as BMS-562247-01. By late 2019, sales of the product by BMS accounted for thirty-percent of their quarterly revenue. In December 2019, the US FDA approved a generic version of apixaban produced jointly