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

Andexanet alfa
Clinical data
Trade namesAndexxa, Ondexxya, others
Other namesCoagulation factor Xa (recombinant), inactivated-zhzo, PRT06445, r-Antidote, PRT4445
AHFS/Drugs.comMultum Consumer Information
Routes of
Intravenous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismNot studied
Elimination half-life5 h to 7 h
CAS Number
  • none

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

It was approved for medical use in the United States in May 2018.[1] It was developed by Portola Pharmaceuticals.[3] As of 2018 it is only available in a few locations and costs between US$25,000 and US$50,000.[4]

Medical usesEdit

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

There are no randomised clinical trials as of 2019. Studies in healthy volunteers show that the molecule binds fXa-inhibitors and counters their anti-fXa-activity.[5] The only published clinical trial is a prospective, open label, single group study.[6] This study reports results on 352 people and demonstrates a reduction of anti-fXa-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.[7] The FDA has demanded a randomised clinical trial: the first results are not expected before 2023.[8]

Adverse effectsEdit

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

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


Mechanism of actionEdit

Andexanet alfa is a biologic agent, a recombinant modified version of human activated factor X (FXa).[9] 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.[3][10] 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.[11]


It was approved in the US in 2018 based on data from two phase III studies on reversing the anticoagulant activity of FXa inhibitors rivaroxaban and apixaban in healthy volunteers.[5] As a condition of its accelerated approval there is a study being conducted comparing it to other currently used reversal agents ("usual care").[12][13]

Society and cultureEdit


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).[14]


  1. ^ a b c d "ANDEXXA package insert" (PDF).
  2. ^ a b c d e f g "Andexxa Monograph for Professionals". Retrieved 19 December 2018.
  3. ^ a b Dolgin E (March 2013). "Antidotes edge closer to reversing effects of new blood thinners". Nature Medicine. 19 (3): 251. doi:10.1038/nm0313-251. PMID 23467222.
  4. ^ "Andexxa - An Antidote for Apixaban and Rivaroxaban | The Medical Letter, Inc". (1549). June 18, 2018. Retrieved 19 December 2018.
  5. ^ a b Siegal, Deborah M.; Curnutte, John T.; Connolly, Stuart J.; Lu, Genmin; Conley, Pamela B.; Wiens, Brian L.; Mathur, Vandana S.; Castillo, Janice; Bronson, Michele D. (2015-12-17). "Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity". New England Journal of Medicine. 373 (25): 2413–2424. doi:10.1056/nejmoa1510991. ISSN 0028-4793. PMID 26559317.
  6. ^ Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al. (2019). "Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors". N Engl J Med. 380 (14): 1326–1335. doi:10.1056/NEJMoa1814051. PMC 6699827. PMID 30730782.
  7. ^ Justin Morgenstern, "Andexanet Alfa: More garbage science in the New England Journal of Medicine", First10EM blog, February 11, 2019. Available at:
  8. ^
  9. ^ Lu, Genmin; DeGuzman, Francis R.; Lakhotia, Sanjay; Hollenbach, Stanley J.; Phillips, David R.; Sinha, Uma (2008-11-16). "Recombinant Antidote for Reversal of Anticoagulation by Factor Xa Inhibitors". Blood. 112 (11): 983–983. ISSN 0006-4971.
  10. ^ Lu G, Deguzman FR, Hollenbach SJ, et al. (March 2013). "A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa". Nature Medicine. 19 (4): 446–51. doi:10.1038/nm.3102. PMID 23455714.
  11. ^ H. Spreitzer (23 December 2013). "Neue Wirkstoffe – Andexanet Alfa". Österreichische Apothekerzeitung (in German) (26/2013): 40.
  12. ^ 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, Jr; ANNEXA-4, Investigators. (4 April 2019). "Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors". The New England journal of medicine. 380 (14): 1326–1335. doi:10.1056/NEJMoa1814051. PMID 30730782.
  13. ^ "Trial of Andexanet in ICH Patients Receiving an Oral FXa Inhibitor - Full Text View -".
  14. ^ "Lexi Comp Drug Information Online". 24 May 2018.