Andexanet alfa

Overview

Andexanet alfa, sold under the brand name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. It has not been found to be useful for other factor Xa inhibitors. It is given by injection into a vein.[1][2] WP

Common side effects include pneumonia and urinary tract infections. Severe side effects may include blood clots, heart attacks, strokes, or cardiac arrest. It works by binding to rivaroxaban and apixaban.[2] WP

It was approved for medical use in the United States in May 2018. It was developed by Portola Pharmaceuticals.[1][3] WP

In December 2025, the FDA issued a drug safety communication in response to postmarketing safety data on thromboembolic events, including serious and fatal outcomes, and determined that the risks of the medication outweigh the benefits. In response, AstraZeneca submitted a request to voluntarily withdraw the Biologics License Application and end commercial sales and manufacturing in the United States by December 22, 2025.[4] WP

Uses, dosage and effects

Medical uses

Andexanet alfa is used to stop life-threatening or uncontrollable bleeding in people who are taking rivaroxaban or apixaban.[1] WP

Studies in healthy volunteers show that the molecule binds factor Xa inhibitors and counters their anti-Xa-activity. The first published clinical trial was a prospective, open label, single group study. This study reports results on 352 people and demonstrates a reduction of anti-Xa-activity while also showing an excellent or good hemostatic efficacy in 82%. While people who were expected to die in 30 days were excluded from the study, 14% of participants died. There was no relationship between hemostatic efficacy and reduced anti-Xa-activity. The FDA demanded a randomised clinical trial which resulted in publication in 2024. The ANNEXA-I trial included 530 patients with intracerebral hemorrhage who were receiving factor Xa inhibitors. Andexanet resulted in better control of hematoma expansion than usual care, but was associated with thrombotic events, including ischemic stroke. ANNEXA-I did not have sufficient power or information to draw conclusions about the effect of andexanet on mortality, clinical deterioration, or the need for rescue therapy.[5–10] WP

Risks and side effects

Adverse effects

Common side effects include pneumonia and urinary tract infections. Severe side effects may include blood clots or cardiac arrest.[2] WP

Andexanet alfa has a boxed warning that it is associated with arterial and venous blood clots, ischemic events, cardiac arrest, and sudden deaths.[1] WP

Pharmacology

Mechanism of action

Andexanet alfa is a biologic agent, a recombinant modified version of human activated factor X (FXa). Andexanet alfa differs from native FXa due to the removal of a 34 residue fragment that contains the Gla domain. This modification reduces andexanet alfa's anticoagulant potential. Additionally, a serine to alanine (S419A) mutation in the active site eliminates its activity as a prothrombin to thrombin catalyst, but still allows the molecule to bind to FXa inhibitors. FXa inhibitors bind to andexanet alfa with the same affinity as to natural FXa. As a consequence, in the presence of andexanet alfa, natural FXa is partially freed, which can lead to effective hemostasis. In other words, it acts as a decoy receptor. Andexanet alfa reverses effect of all anticoagulants that act directly through FXa or by binding antithrombin III. The drug is not effective against factor IIa inhibitor dabigatran. Its activity is measured using the anti-Xa test, which is utilized to determine the amount of available factor Xa for coagulation[3][11–15] WP

History

History

It was approved in the United States in 2018 based on data from two phase III studies on reversing the anticoagulant activity of FXa inhibitors rivaroxaban and apixaban in healthy volunteers. As a condition of its accelerated approval, the ANNEXA-I study was conducted comparing it to other currently used reversal agents ("usual care").[5][6][16] WP

Andexanet alfa was voluntarily withdrawn from the market by the manufacturer following safety concerns expressed by the FDA. Production and distribution was ended December 22, 2025.[4] WP

Legal status

Economics

Initial pricing (AWP) is $58,000 per reversal (800 mg bolus + 960 mg infusion, $3,300 per 100 mg vial) which is higher than reversal agents for other DOAC agents (idarucizumab for use in dabigatran reversal is $4,200 per reversal).[17] WP

Chemistry

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Andexxa- andexanet alfa injection, powder, lyophilized, for solution. 21 September 2020
2. Other Andexxa Monograph for Professionals
3. Journal / agency Dolgin E. Antidotes edge closer to reversing effects of new blood thinners. Nature Medicine. March 2013. doi:10.1038/nm0313-251 · PMID 23467222
4. Journal / agency Update on the Safety of Andexxa - FDA Safety Communication – December 18, 2025
5. Journal / agency Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. The New England Journal of Medicine. December 2015. doi:10.1056/NEJMoa1510991 · PMID 26559317
6. Journal / agency Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. The New England Journal of Medicine. April 2019. doi:10.1056/NEJMoa1814051 · PMID 30730782 · PMC6699827
7. Other Morgenstern J. Andexanet Alfa: More garbage science in the New England Journal of Medicine. 11 February 2019
8. Other ClinicalTrialsGov NCT03661528 A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor
9. Journal / agency Connolly SJ, Sharma M, Cohen AT, Demchuk AM, Członkowska A, Lindgren AG, Molina CA, Bereczki D, Toni D, Seiffge DJ, Tanne D, Sandset EC, Tsivgoulis G, Christensen H, Beyer-Westendorf J, Coutinho JM, Crowther M, Verhamme P, Amarenco P, Roine RO, Mikulik R, Lemmens R, Veltkamp R, Middeldorp S, Robinson TG, Milling TJ, Tedim-Cruz V, Lang W, Himmelmann A, Ladenvall P, Knutsson M, Ekholm E, Law A, Taylor A, Karyakina T, Xu L, Tsiplova K, Poli S, Kallmünzer B, Gumbinger C, Shoamanesh A. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. The New England Journal of Medicine. May 2024. doi:10.1056/NEJMoa2313040 · PMID 38749032
10. Journal / agency Smith WS, Hemphill JC. Reversing Oral Anticoagulation in Intracerebral Hemorrhage. The New England Journal of Medicine. May 2024. doi:10.1056/NEJMe2403726 · PMID 38749038
11. Journal / agency Lu G, DeGuzman FR, Lakhotia S, Hollenbach SJ, Phillips DR, Sinha U. Recombinant Antidote for Reversal of Anticoagulation by Factor Xa Inhibitors. Blood. 16 November 2008. doi:10.1182/blood.V112.11.983.983
12. Journal / agency Kaatz S, Bhansali H, Gibbs J, Lavender R, Mahan CE, Paje DG. Reversing factor Xa inhibitors - clinical utility of andexanet alfa. Journal of Blood Medicine. 13 September 2017. doi:10.2147/JBM.S121550 · PMID 28979172 · PMC5602457
13. Journal / agency Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Sinha U. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nature Medicine. April 2013. doi:10.1038/nm.3102 · PMID 23455714
14. Journal / agency Spreitzer H. Neue Wirkstoffe – Andexanet Alfa. Österreichische Apothekerzeitung. 23 December 2013
15. Journal / agency Flaherty D, Connors JM, Singh S, Sylvester KW, Rimsans J, Cornella L. Andexanet Alfa for Urgent Reversal of Apixaban Before Aortic Surgery Requiring Cardiopulmonary Bypass: A Case Report. A&A Practice. October 2019. doi:10.1213/XAA.0000000000001052 · PMID 31265446
16. Other ClinicalTrialsGov NCT03661528 Trial of Andexanet in ICH Patients Receiving an Oral FXa Inhibitor
17. Other Lexi Comp Drug Information Online. 24 May 2018

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