Andexanet alfa for the reversal of factor Xa inhibitors

Favresse, Julien; Hardy, Michaël; Dievoet, Marie-Astrid van; Sennesael, Anne-Laure; Douxfils, Jonathan; Samama, Charles Marc; Vornicu, Ovidiu Ionut; Dincq, Anne-Sohie; Lessire, Sarah; Mullier, François

doi:10.1080/14712598.2019.1599355

Cited by 11 publications

(11 citation statements)

References 86 publications

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“…Since the initial publication of the guidance, a specific reversal agent, andexanet alfa, was approved in the United States for rivaroxaban and apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding, and has also been approved by the Committee for Medicinal Products for Human Use in Europe for the same application. 3,73 There are two dosing strategies (low and high dose), as a bolus followed by a continuous infusion. This reversal agent will reduce the levels of direct FXa inhibitors, as measured by calibrated chromogenic anti-Xa activity.…”

Section: Doac Reversal Agents Andexanet Alfamentioning

confidence: 99%

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

Adcock²,

et al. 2021

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In 2018, the International Council for Standardization in Hematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alpha. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author’s personal experience/expert opinion and (3) good laboratory practice.

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Section: Doac Reversal Agents Andexanet Alfamentioning

confidence: 99%

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

Adcock²,

et al. 2021

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“…38 Nevertheless, the andexanet alfa PI does not advocate pretreatment FXa DOAC levels, even if noted exceptions for drug efficacy was reported for select patients with high baseline values. [39][40][41] Such situations are not isolated and, as mentioned, several cases reports mentioned dabigatran exposure as high as 3000 ng/ml and rivaroxaban exposure as high as 2500 ng/ml. 36,42 This is not so occasional; in our own laboratories, levels close to 2500 ng/ml have also been measured in some patients.…”

Section: Essentialsmentioning

confidence: 99%

“…In the ANNEXA‐4 trial, subjects with acute bleeding events with rivaroxaban or apixaban levels of >75 ng/ml were eligible for enrollment, suggesting lower DOACs exposure would not require to be reversed by andexanet 38 . Nevertheless, the andexanet alfa PI does not advocate pretreatment FXa DOAC levels, even if noted exceptions for drug efficacy was reported for select patients with high baseline values 39–41 …”

Section: What Is the Role Of The Laboratory In Doac Therapy?mentioning

confidence: 99%

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The myths behind DOAC measurement: Analyses of prescribing information from different regulatory bodies and a call for harmonization

Gosselin

Favaloro

Douxfils

2022

Journal of Thrombosis and Haemostasis

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For more than a decade, US laboratories have failed to implement solutions to help their clinicians in managing complex situations or patients on direct oral anticoagulants (DOACs). The problem may find different origins, among which is the position of the Food and Drug Administration, which categorized these drugs as monitoring‐ and measurement‐free, whereas other regulatory bodies like the European Medicines Agency or the Therapeutic Goods Administration in Australia were more conservative on the principle that the absence of proof (of monitoring/measurement benefits) is not proof of an absence (of monitoring/measurement needs). Pivotal clinical studies that led to the approval of DOACs were presented as devoid of such testing, although some companies considered monitoring as a solution to improve their benefit/risk ratio. In this JTH In Clinics issue, we report more than a decade of development that has permitted the activation of smart laboratory solutions to qualify or quantify DOACs and discuss myths and misconceptions around technical and regulatory requirements that support the current reluctance of implementing these technologies in most US laboratories. Use of DOACs is ever expanding, with DOAC prescriptions now exceeding those of other anticoagulants, including vitamin K antagonists, in some geographies. As this use increases, the likely need to measure DOAC exposure will also increase. Measurement of DOACs does not represent any technical difficulty. That these laboratory tests are not available in some locations suggests disparities in patient care, and we suggest it is time to address such inequalities.

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“…Currently, andexanet alfa has been shown to have a reversing effect on FXa inhibitors, although some areas of uncertainty still exist. While reviews of andexanet alfa have been published between 2008 and 2019, 6–21 none include full data from the pivotal real-world trial of andexanet alfa. This article will review the data supporting andexanet alfa, encompassing all andexanet alfa clinical trials, including real world clinical use, and discuss implications for the clinical use of andexanet alfa.…”

Section: Introductionmentioning

confidence: 99%

Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation

Carpenter

Singh

Dietrich

et al. 2019

Therapeutic Advances in Drug Safety

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Background: Review of clinical data on andexanet alfa for the reversal of factor Xa (FXa) inhibitor associated anticoagulation. Data sources: In the present review, we identified articles via PubMed using the combined keywords andexanet alfa, apixaban, enoxaparin, edoxaban, and rivaroxaban. Additional online searches via PubMed, Google Scholar, and Lexicomp were conducted for both prescribing and cost information. Portola Pharmaceuticals was contacted for information used for United States Food and Drug Administration approval of andexanet alfa. Study selection and data extraction: English-language clinical trials and reviews published between January 2008 and April 2019 were included for review. Bibliographies of selected articles were reviewed manually for relevant publications, focusing on reversal strategies for apixaban, enoxaparin, edoxaban, or rivaroxaban associated anticoagulation using andexanet alfa. Review articles were excluded. Data synthesis: The safety and tolerability of andexanet alfa were evaluated in one phase I, two phase II, and one phase III clinical trials. The use of andexanet alfa for reversing FXa inhibitor-associated anticoagulation were evaluated in the phase III ANNEXA-4 study. Conclusions: Studies evaluating laboratory parameters for coagulation show that andexanet alfa rapidly neutralizes the anticoagulant effects of apixaban, enoxaparin, edoxaban, and rivaroxaban. Clinical studies show that andexanet alfa improves markers related to coagulation, and reverses major bleeding in healthy volunteers and patients with life-threatening bleeding. Interruption of anticoagulation may result in thromboembolic and ischemic events. The use of andexanet alfa requires close monitoring for signs and symptoms of thromboembolic events, ischemic events, and cardiac arrest. Furthermore, anticoagulation should be resumed following the administration of andexanet alfa as soon as medically appropriate.

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Andexanet alfa for the reversal of factor Xa inhibitors

Cited by 11 publications

References 86 publications

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

The myths behind DOAC measurement: Analyses of prescribing information from different regulatory bodies and a call for harmonization

Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation

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