Andexanet alfa

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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
administration
Intravenous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismNot studied
Elimination half-life5 h to 7 h
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
KEGG
ChEMBL

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]

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 uses[edit]

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

Adverse effects[edit]

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]

Pharmacology[edit]

Mechanism of action[edit]

Andexanet alfa is a biologic agent, a recombinant modified version of human activated factor X (FXa).[5] 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][6] 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.[7]

History[edit]

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.[8]

Society and culture[edit]

Economics[edit]

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).[9]

References[edit]

  1. ^ a b c d "ANDEXXA package insert" (PDF).
  2. ^ a b c d e f g "Andexxa Monograph for Professionals". Drugs.com. 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". secure.medicalletter.org (1549). June 18, 2018. Retrieved 19 December 2018.
  5. ^ 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.
  6. ^ 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.
  7. ^ H. Spreitzer (23 December 2013). "Neue Wirkstoffe – Andexanet Alfa". Österreichische Apothekerzeitung (in German) (26/2013): 40.
  8. ^ 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.
  9. ^ "Lexi Comp Drug Information Online". 24 May 2018.