Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation

Carpenter, Elise M. L.; Singh, Divita; Dietrich, Eric; Gums, John G.

doi:10.1177/2042098619888133

Cited by 38 publications

(38 citation statements)

References 33 publications

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“…None of these drugs are directed against other types of anticoagulants or antiplatelet and radiocontrast agents [ 2 ]. In addition to these shortcomings, andexanet alfa tends to be expensive (between US$29,700 and US$59,400 for a treatment) and presents an 18% risk of thrombosis [ 16 ]. An alternative is the prothrombin complex concentrate product, which may be used off-label for the treatment of life-threatening hemorrhaging and costs US$9695 per treatment [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to these shortcomings, andexanet alfa tends to be expensive (between US$29,700 and US$59,400 for a treatment) and presents an 18% risk of thrombosis [ 16 ]. An alternative is the prothrombin complex concentrate product, which may be used off-label for the treatment of life-threatening hemorrhaging and costs US$9695 per treatment [ 16 ]. While no good analysis has been published to our knowledge for hemadsorption, one may eventually extrapolate its cost from hemodialysis data.…”

Section: Discussionmentioning

confidence: 99%

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In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

et al. 2020

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Background and Objective Based on previous experience of sorbent-mediated ticagrelor, dabigatran, and radiocontrast agent removal, we set out in this study to test the effect of two sorbents on the removal of edoxaban, a factor Xa antagonist direct oral anticoagulant. Methods We circulated 100 mL of edoxaban solution during six first-pass cycles through 40-mL sorbent columns (containing either CytoSorb in three passes or Porapak Q 50–80 mesh in the remaining three passes) during experiments using human plasma and 4% bovine serum albumin solution as drug vehicles. Drug concentration was measured by liquid chromatography-tandem mass spectrometry. Results Edoxaban concentration in two experiments performed with human plasma dropped from 276.8 to 2.7 ng/mL and undetectable concentrations, respectively, with CytoSorb or Porapak Q 50–80 mesh ( p = 0.0031). The average edoxaban concentration decreased from 407 ng/mL ± 216 ng/mL to 3.3 ng/mL ± 7 ng/mL ( p = 0.017), for a removal rate of 99% across all six samples of human plasma (two samples) and bovine serum albumin solution (four samples). In four out of the six adsorbed samples, the drug concentrations were undetectable. Conclusion Sorbent-mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution. Electronic supplementary material The online version of this article (10.1007/s40268-020-00308-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

et al. 2020

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“…68 Further evidence is needed to establish the role of andexanet alpha in the management of LMWH-associated ICH; trials are ongoing. 69 ICH, intracerebral haemorrhage.…”

Section: Heparinmentioning

confidence: 99%

Acute intracerebral haemorrhage: diagnosis and management

et al. 2020

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Intracerebral haemorrhage (ICH) accounts for half of the disability-adjusted life years lost due to stroke worldwide. Care pathways for acute stroke result in the rapid identification of ICH, but its acute management can prove challenging because no individual treatment has been shown definitively to improve its outcome. Nonetheless, acute stroke unit care improves outcome after ICH, patients benefit from interventions to prevent complications, acute blood pressure lowering appears safe and might have a modest benefit, and implementing a bundle of high-quality acute care is associated with a greater chance of survival. In this article, we address the important questions that neurologists face in the diagnosis and acute management of ICH, and focus on the supporting evidence and practical delivery for the main acute interventions.

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“…8,10,15 Andexanet is the only product available on the market with supporting data; however, there are only few published in vitro studies assessing the use of andexanet for reversal of UFH. 10,12-15…”

Section: Andexanet Alfa For Reversal Of Ufhmentioning

confidence: 99%

“…Carpenter et al 14 mention that although andexanet can reverse the effects of UFH, its use is limited considering the significant difference in cost relative to protamine. 14 The average wholesale price (AWP) unit price of 25 mL (10 mg/mL) of protamine is $1.77. 5 The AWP unit price of the 100-mg powder for solution of Andexxa ® is $3300.…”

Section: Andexanet Alfa For Reversal Of Ufhmentioning

confidence: 99%

Andexanet Alfa, the Possible Alternative to Protamine for Reversal of Unfractionated Heparin

Maneno

Ness

2020

Ann Pharmacother

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The recent shortage of protamine prompted an investigation of alternatives for reversal of unfractionated heparin. Heparin is an anticoagulant utilized in the hospital setting. Available options for anticoagulation include direct oral anticoagulants, vitamin K antagonists, thrombin inhibitors, low-molecular-weight heparins, and heparin. Protamine is the approved reversal agent for heparin with few alternatives under investigation. Although andexanet was designed as an antidote for apixaban and rivaroxaban, in vitro studies show that in a dose-dependent technique, andexanet had near full reversal of heparin, reversed anti–factor Xa activity, and neutralized anticoagulant effects of activated partial thromboplastin time and thrombin time induced by heparin.

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Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation

Cited by 38 publications

References 33 publications

In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

Acute intracerebral haemorrhage: diagnosis and management

Andexanet Alfa, the Possible Alternative to Protamine for Reversal of Unfractionated Heparin

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