Skip to main content

Unfortunately we don't fully support your browser. If you have the option to, please upgrade to a newer version or use Mozilla Firefox, Microsoft Edge, Google Chrome, or Safari 14 or newer. If you are unable to, and need support, please send us your feedback.

We'd appreciate your feedback.Tell us what you think! opens in new tab/window

Elsevier
Publish with us
AI-Generated response:

How do I reverse Apixaban (Eliquis)?

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

To reverse Apixaban (Eliquis), administer Andexanet alfa or consider Prothrombin Complex Concentrate (PCC) if Andexanet alfa is unavailable.

Andexanet alfa is specifically indicated for life-threatening or uncontrolled bleeding but is expensive and not available in all hospitals.[1-5]

  • Administer Andexanet alfa as a 400 mg IV bolus followed by a 4 mg/minute infusion for up to 120 minutes if the last dose of Apixaban was 5 mg or less, or if the last dose was taken more than 8 hours prior.[1-3]

  • For higher doses of Apixaban (more than 5 mg) or if the last dose was taken within 8 hours, administer an 800 mg IV bolus of Andexanet alfa followed by an 8 mg/minute infusion for up to 120 minutes.[1-3]

  • Prothrombin Complex Concentrate (PCC) may be considered if Andexanet alfa is not available, although it has not been evaluated in clinical trials for this specific use.[4-6]

  • Activated charcoal can be used to reduce absorption if Apixaban overdose or accidental ingestion is suspected, especially within a few hours of ingestion.[5-6]

  • It is important to note that common reversal agents like Protamine sulfate and Vitamin K are not effective for reversing Apixaban.[5]

Additional info

When considering the reversal of Apixaban, it is crucial to assess the timing and dose of the last Apixaban intake to determine the appropriate reversal strategy. Andexanet alfa, a recombinant modified human factor Xa decoy protein, is the preferred agent due to its specific mechanism of action in sequestering the factor Xa inhibitors. However, its high cost and limited availability can be a barrier. In such cases, PCC, which contains factors II, VII, IX, and X, can be used as an alternative, although its use in this context lacks robust clinical trial data. Monitoring for effectiveness of reversal should focus on clinical improvement and stabilization of the patient's condition, as traditional coagulation tests (PT, INR, aPTT) are not reliable indicators of the anticoagulation effect of Apixaban when PCCs are used. Always consider the patient's overall clinical status and the risks of thrombosis when reversing anticoagulation.

References

Reference 1

1.

Weitz, Jeffrey I. (2022). In Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine (pp. 1766). DOI: 10.1016/B978-0-323-72219-3.00095-5

Andexanet alfa is available for reversal of rivaroxaban, apixaban, and edoxaban. A recombinant variant of factor Xa without catalytic activity, andexanet serves as a decoy to sequester oral factor Xa inhibitors until they are cleared from the circulation.Low- or high-dose intravenous andexanet regimens are used. The low-dose regimen starts with a bolus of 400 mg followed by an infusion of 4 mg/min for up to 120 minutes, whereas the high-dose regimen starts with a bolus of 800 mg followed by an infusion of 8 mg/min for up to 120 minutes.The low-dose regimen is used for reversal of doses of rivaroxaban or apixaban of 10 mg or 5 mg or less, respectively, or for any dose of rivaroxaban or apixaban if the last dose was taken more than 8 hours prior to presentation. The high-dose regimen is used to reverse rivaroxaban or apixaban doses over 10 and 5 mg, respectively, if the last dose was taken less than 8 hours since presentation, or for reversal if the dose of rivaroxaban or apixaban or the timing of the last dose is unknown (seeTable 95.11). Andexanet alfa is expensive and is not available in all hospitals. Because of its cost, andexanet alfa is often reserved for reversal in patients with intracranial bleeds or for bleeds into a closed space such as retroperitoneal or pericardial bleeds.

Reference 2

2.

Elsevier ClinicalKey Clinical Overview

Treatment Administer vitamin K concurrently. Repeat dosing is not recommended. Reversal of direct oral anticoagulant therapy in patients with life-threatening bleeding or need for emergent procedural intervention Direct thrombin inhibitor (eg, dabigatran) reversal Idarucizumab Idarucizumab Solution for injection; Adults: 5 g IV as a single dose. Data supporting an additional dose are limited. Prothrombin complex concentrates may be administered as an alternative if idarucizumab is unavailable Prothrombin, Coagulation Factor VII (Pooled Human Plasma), Coagulation Factor IX (Pooled Human Plasma), High Purity, Coagulation Factor X (Pooled Human Plasma), Protein C Concentrate (Human), Protein S Concentrate (Human) Solution for injection; Adults: 50 units factor IX/kg (Max: 4,000 units) IV as a single dose. Factor Xa inhibitor (eg, apixaban, rivaroxaban, or edoxaban) reversal Dose of andexanet alfa is dependent on anticoagulant agent as well as dose and timing of last administration Coagulation Factor Xa (Recombinant), Inactivated Solution for injection; Adults: 400 mg IV bolus, then 4 mg/minute continuous IV infusion for up to 120 minutes for reversal of apixaban 5 mg or less or rivaroxaban 10 mg or less given within 8 hours; or unknown timing or for any dose of apixaban or rivaroxaban given 8 hours or more prior to reversal.

Reference 3

3.

Elsevier ClinicalKey Clinical Overview

Treatment Administer vitamin K concurrently. Repeat dosing is not recommended. Reversal of direct acting oral anticoagulant therapy in patients with life-threatening bleeding or need for emergent procedural intervention Direct thrombin inhibitor (eg, dabigatran) reversal Idarucizumab Idarucizumab Solution for injection; Adults: 5 g IV as a single dose. Data supporting an additional dose are limited. Prothrombin complex concentrate may be administered as an alternative if idarucizumab is unavailable Prothrombin, Coagulation Factor VII (Pooled Human Plasma), Coagulation Factor IX (Pooled Human Plasma), High Purity, Coagulation Factor X (Pooled Human Plasma), Protein C Concentrate (Human), Protein S Concentrate (Human) Solution for injection; Adults: 50 units factor IX/kg (Max: 4,000 units) IV as a single dose. Factor Xa inhibitor (eg, apixaban, rivaroxaban, or edoxaban) reversal Dose of andexanet alfa is dependent on anticoagulant agent as well as dose and timing of last administration Coagulation Factor Xa (Recombinant), Inactivated Solution for injection; Adults: 400 mg IV bolus, then 4 mg/minute continuous IV infusion for up to 120 minutes for reversal of apixaban 5 mg or less or rivaroxaban 10 mg or less given within 8 hours; or unknown timing or for any dose of apixaban or rivaroxaban given 8 hours or more prior to reversal. Coagulation Factor Xa (Recombinant), Inactivated Solution for injection; Adults: 800 mg IV bolus, then 8 mg/minute continuous IV infusion for up to 120 minutes for reversal of apixaban more than 5 mg, rivaroxaban more than 10 mg, or unknown dose given within 8 hours or unknown timing prior to reversal; and for reversal of edoxaban.

Reference 4

4.

Elsevier ClinicalKey Drug Class Overview

Content last updated: August 1, 2023.

Specific agents for reversal of anticoagulation with edoxaban are not currently available. Vitamin K or phytonadione is FDA-approved for warfarin- induced prothrombin deficiency; intravenous vitamin K administration is recommended for warfarin reversal in major bleeding events while oral administration is recommended in nonmajor bleeding events that require hospitalization. Idarucizumab, a monoclonal antibody, is indicated for reversal of dabigatran's anticoagulant effect for patients who require emergency surgery or urgent procedures and those with life-threatening or uncontrolled bleeding. Factor Xa, inactivated is indicated for the reversal of the anticoagulant effects of apixaban and rivaroxaban for patients experiencing life-threatening or uncontrolled bleeding. Guidelines suggest the use of 4-factor prothrombin complex concentrate (PCC) for major bleeding in patients taking a vitamin K antagonist or factor Xa inhibitor and in patients taking dabigatran, if idarucizumab is not available[22934]. [51249][60212][63132][63244]

Reference 5

5.

Food and Drug Administration (DailyMed).

Publish date: May 2, 2024.

Warnings And Cautions Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS (apixaban) in patients with active pathological hemorrhage. Reversal of Anticoagulant Effect An agent to reverse the anti-factor Xa activity of ELIQUIS (apixaban) is available. The pharmacodynamic effect of ELIQUIS (apixaban) can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies [see Clinical Pharmacology (12.2) ]. When PCCs are used, monitoring for the anticoagulation effect of ELIQUIS (apixaban) using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and is not recommended. Activated oral charcoal reduces absorption of ELIQUIS (apixaban), thereby lowering ELIQUIS (apixaban) plasma concentration [see Overdosage (10)]. Hemodialysis does not appear to have a substantial impact on ELIQUIS (apixaban) exposure [see Clinical Pharmacology (12.3) ]. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of ELIQUIS (apixaban). There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving ELIQUIS (apixaban). There is no experience with systemic hemostatics (desmopressin) in individuals receiving ELIQUIS (apixaban), and they are not expected to be effective as a reversal agent.

Overdosage 10 OVERDOSAGE Overdose of ELIQUIS (apixaban) increases the risk of bleeding [see Warnings and Precautions (5.2) ]. In controlled clinical trials, orally administered ELIQUIS (apixaban) in healthy subjects at doses up to 50 mg daily for 3 to 7 days (25 mg twice daily for 7 days or 50 mg once daily for 3 days) had no clinically relevant adverse effects. In healthy subjects, administration of activated charcoal 2 and 6 hours after ingestion of a 20-mg dose of ELIQUIS (apixaban) reduced mean ELIQUIS (apixaban) AUC by 50% and 27%, respectively. Thus, administration of activated charcoal may be useful in the management of ELIQUIS (apixaban) overdose or accidental ingestion. An agent to reverse the anti-factor Xa activity of ELIQUIS (apixaban) is available.

Reference 6

6.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Contraindications And Precautions Eliquis is contraindicated in any patient with active pathological bleeding, as eliquis use increases the risk of bleeding and can cause serious and potentially fatal bleeding. The concomitant use of other drugs that affect hemostasis (e.g., aspirin and other antiplatelet drugs, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs) increases the risk of bleeding. Educate patients about the signs and symptoms of bleeding, and advise them to report bleeding immediately or to go to an emergency room. Discontinue eliquis in patients with active pathological bleeding. A reversal agent, factor Xa, is available when the reversal of the anticoagulant effect of eliquis is necessary due to life-threatening or uncontrolled bleeding. The effects of eliquis can persist for at least 24 hours after the last dose. Activated oral charcoal reduces absorption and lowers the plasma concentration of eliquis and may be useful in eliquis overdose or accidental ingestion. Although not evaluated in clinical trials, the use of procoagulant reversal agents (e.g., prothrombin complex concentrate [PCC], activated prothrombin complex concentrate, or recombinant factor VIIa) may be considered. Monitoring for the anticoagulation effect of eliquis using a clotting test (e.g., PT, INR, aPTT) or anti-factor Xa activity is not useful or recommended when PCCs are used. The effects of 4-factor PCCs on steady state eliquis pharmacodynamics have been studied in healthy subjects. Endogenous thrombin potential (ETP) returned to pre-eliquis baseline concentrations 4 hours after the initiation of a 30-minute PCC infusion compared to 45 hours after a placebo infusion. Mean ETP concentrations continued to increase and exceeded baseline concentrations, reaching a maximum (34% to 51% increase) 21 hours after PCC initiation.

Follow up questions