In 2007,Pfizer andBristol-Myers Squibb began the development of apixaban as an anticoagulant.[13] Apixaban was approved for medical use in the European Union in May 2011, and in the United States in December 2012.[7][8][14] It is on theWorld Health Organization's List of Essential Medicines.[15] In 2023, it was the 28th most commonly prescribed medication in the United States, with more than 19million prescriptions.[16][17] It is available as a generic medication, although not in the United States.[10][18]
For extended treatment to reduce risk of recurring VTE after initial therapy in patients with high risk of recurrence, such as patients with active cancer or those with unprovoked VTE.[24][25][26][27][28][29]
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 withnon-valvular atrial fibrillation (NVAF) with one or more risk factors, for the treatment of deep vein thrombosis and pulmonary embolism in adults, and for the prevention of recurrent DVT and PE in adults.[7]
While data are limited for the use of apixaban in people with severely decreased kidney function and those onhemodialysis, studies are investigating its potential as an alternative to standard therapy,vitamin K antagonists. However, optimal dosing in these populations is yet to be determined.[36]
Following spinal anesthesia or puncture, people who are being treated with anti-thrombotic agents are at higher risk for developing ahematoma, which causes long-term or permanent paralysis. The risk of this may be increased by using epidural or intrathecalcatheters after a surgical operation or from the concurrent use of medicinal agents that affecthemostasis.[6]
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 forfibrin clot formation.[45] Apixaban has no direct effect onplatelet aggregation, but by inhibiting factor Xa, it indirectly decreases clot formation induced by thrombin.[6]
Apixaban was approved for medical use in the European Union in May 2011.[7]
Anew drug application (NDA) for the approval of apixaban was submitted to the USFood and Drug Administration (FDA) byBristol-Myers Squibb (BMS) andPfizer jointly after the conclusion of the ARISTOTLE clinical trial in 2011.[46][14] Apixaban was approved for the prevention of stroke in people with atrial fibrillation in December 2012.[14][47] In 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.[48][49] In August 2014, the FDA approved apixaban for the additional indication of the treatment of recurring deep vein thrombosis and pulmonary embolism.[48][50] During its development the drug was known as BMS-562247-01.[51] By late 2019, sales of the product by BMS accounted for thirty percent of their quarterly revenue.[52]
In December 2019, the US FDA approved a generic version of apixaban produced jointly byMylan and Micro Labs.[53][52][10] BMS and Pfizer worked quickly to block generics from being created, and in August 2020, they won a patent infringement lawsuit againstSigmapharm, Sunshine Lake, andUnichem, after previously settling patent cases against 25 other companies.[54][55] In September 2021, aFederal Circuit Court upheld the ruling.[56] The result is that apixaban generics will most likely not be available in the United States until at least 2026, but possibly 2031.[18]
In July 2022, the Canadian generic drug company,Apotex Inc., obtained approval for marketing of apixaban.[57][58]
Pfizer reported revenue ofUS$6.747 billion for Eliquis in 2023.[59]
Apixaban is one of ten medications covered by price negotiations in the US under theInflation Reduction Act. The negotiations, conducted by theCenters for Medicare & Medicaid Services, apply to pricing forMedicare recipients. The results of the negotiations were announced in August 2024, and Medicare's negotiated price for a 30-day supply of Eliquis is $231, a 56% decrease from the 2023 list price of $521.[60] The pricing is set to take effect in 2026.[61][62]
^abcd"Eliquis EPAR".European Medicines Agency. 17 September 2018. Retrieved22 April 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^abcGranger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. (September 2011). "Apixaban versus warfarin in patients with atrial fibrillation".The New England Journal of Medicine.365 (11):981–992.doi:10.1056/NEJMoa1107039.PMID21870978.
^Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al. (March 2011). "Apixaban in patients with atrial fibrillation".The New England Journal of Medicine.364 (9):806–817.doi:10.1056/NEJMoa1007432.PMID21309657.
^Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P (March 2010). "Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial".Lancet.375 (9717):807–815.doi:10.1016/S0140-6736(09)62125-5.PMID20206776.
^Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM (December 2010). "Apixaban versus enoxaparin for thromboprophylaxis after hip replacement".The New England Journal of Medicine.363 (26):2487–2498.doi:10.1056/NEJMoa1006885.PMID21175312.
^abConnolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. (September 2009). "Dabigatran versus warfarin in patients with atrial fibrillation".The New England Journal of Medicine.361 (12):1139–1151.doi:10.1056/NEJMoa0905561.hdl:11343/221723.PMID19717844.
^Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, et al. (November 2012). "Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial".European Heart Journal.33 (22):2821–2830.doi:10.1093/eurheartj/ehs274.PMID22933567.
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