Apixaban, sold under the brand name Eliquis, is an
anticoagulant medication used to treat and prevent
blood clots and to prevent
stroke in people with nonvalvular
atrial fibrillation through directly inhibiting
factor Xa.[6][7][8] Specifically, it is used to prevent blood clots following
hip or
knee replacement and in those with a history of prior clots.[6][8] It is used as an alternative to
warfarin and does not require monitoring by blood tests[6] or dietary restrictions.[9] It is taken
by mouth.[6]
In 2007,
Pfizer and
Bristol-Myers Squibb began development of apixaban as an anticoagulant.[11] Apixaban was approved for medical use in the European Union in May 2011, and in the United States in December 2012.[5][6][12] It is on the
World Health Organization's List of Essential Medicines.[13] In 2021, it was the 33rd most commonly prescribed medication in the United States with more than 17million prescriptions.[14][15] It is available as a generic medication, although not in the United States.[8][16]
To reduce the risk of recurring DVT and PE after initial therapy.
In the EU, apixaban is indicated for the prevention of venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery, the prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation (NVAF) with one or more risk factors, for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults, and for the prevention of recurrent DVT and PE in adults.[5]
Atrial fibrillation
Apixaban is recommended by the
National Institute for Health and Clinical Excellence for the prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation and at least one of the following risk factors: prior stroke or transient ischemic attack, age 75 years or older,
diabetes, or symptomatic
heart failure.[17]
Apixaban and other anticoagulants (
dabigatran,
edoxaban and
rivaroxaban) appear equally effective as warfarin in preventing non-hemorrhagic stroke in people with atrial fibrillation and are associated with lower risk of intracranial bleeding.[18][19]
While apixaban may be used in people with severely decreased kidney function and those on hemodialysis it has not been studied in these groups.[6]
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.[4]
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.[25] Apixaban has no direct effect on
platelet aggregation, but by inhibiting factor Xa, it indirectly decreases clot formation induced by thrombin.[4]
History
Apixaban was approved for medical use in the European Union in May 2011.[5]
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.[26][12] Apixaban was approved for the prevention of stroke in people with atrial fibrillation on 28 December 2012.[12][27] 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.[28][29] On 21 August 2014, the FDA approved apixaban for the additional indication of the treatment of recurring deep vein thrombosis and pulmonary embolism.[28][30] During its development the drug was known as BMS-562247-01.[31] By late 2019, sales of the product by BMS accounted for thirty-percent of their quarterly revenue.[32]
Society and culture
Economics
In December 2019, the US FDA approved a generic version of apixaban produced jointly by
Mylan and Micro Labs.[33][32][8] BMS and Pfizer worked quickly to block generics from being created, and in August 2020, they won a patent infringement lawsuit against
Sigmapharm, Sunshine Lake, and
Unichem, after previously settling patent cases against 25 other companies.[34][35] In September 2021, a
Federal Circuit Court upheld the ruling.[36] The result is that apixaban generics will most likely not be available in the United States until at least 2026, but possibly 2031.[16]
In July 2022, the Canadian generic drug company,
Apotex Inc., obtained approval for marketing of apixaban.[37][38]
Apixaban is one of the ten medications proposed for price negotiations in the US under the
Inflation Reduction Act. According to Bristol Myers Squibb the average pay per month per patient for Eliquis is US$55.[39]
^World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization.
hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.