About This Tool

The Andexxa Dosing Calculator is designed to assist healthcare professionals in determining the appropriate dosing regimen for Andexxa (andexanet alfa). This medication is indicated for patients treated with the Factor Xa inhibitors apixaban and rivaroxaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

This guide provides supplementary information regarding the tool's outputs, usage, dosing principles, and key safety considerations. It is not a substitute for the official prescribing information or independent clinical judgment.

Understanding the Outputs

Based on the selected Factor Xa inhibitor, its dose, and the time since administration, the calculator provides one of three potential outcomes:

• Low-Dose Regimen: Recommended for patients on lower doses of apixaban (≤ 5 mg) or rivaroxaban (≤ 10 mg). It specifies a 400 mg IV bolus followed by a 4 mg/min infusion.
• High-Dose Regimen: Recommended for patients on higher doses of apixaban (> 5 mg), rivaroxaban (> 10 mg), or if the dose is unknown. It specifies an 800 mg IV bolus followed by an 8 mg/min infusion.
• Reconsideration Advised: If the last dose of the Factor Xa inhibitor was taken 8 or more hours prior, the anticoagulant effect may be diminished, and reversal with Andexxa may not be necessary. The tool advises clinical assessment and suggests the low-dose regimen if reversal is still deemed necessary.

How to Use the Calculator

To obtain a dosing recommendation, follow these three steps:

• Step 1: Select Factor Xa Inhibitor: Choose between Apixaban (Eliquis) or Rivaroxaban (Xarelto).
• Step 2: Select Inhibitor Dose: From the dropdown menu that appears, select the dose of the Factor Xa inhibitor the patient was taking. If the exact dose is not known, select "Unknown Dose".
• Step 3: Select Time Since Last Dose: Indicate whether the last dose was taken less than 8 hours ago (or if the time is unknown) or 8 or more hours ago.

Once all fields are completed, the "Calculate Dose" button will become active.

Dosing Overview

Andexxa dosing is determined by the specific Factor Xa inhibitor and the dose the patient was receiving prior to the bleeding event. Both regimens consist of an initial intravenous (IV) bolus administered at a target rate of 30 mg/min, followed immediately by a continuous IV infusion lasting 120 minutes.

• Low Dose: 400 mg IV bolus, followed by a 480 mg infusion at 4 mg/min.
• High Dose: 800 mg IV bolus, followed by a 960 mg infusion at 8 mg/min.

The choice between the low and high dose is critical for balancing efficacy with potential risks. The time since the last dose of the anticoagulant is a key factor in determining the necessity of reversal.

Resuming Anticoagulation

After Andexxa administration and stabilization of the patient's bleeding, a decision must be made on when to resume anticoagulation to prevent thromboembolic events. The timing should be individualized based on the patient's thrombotic risk versus the risk of recurrent bleeding. According to the prescribing information, anticoagulant therapy should be resumed as soon as medically appropriate following treatment.

Administration Considerations

Andexxa is an acute-care medication administered in an emergency setting; the concept of a "missed dose" does not apply in the conventional sense. It is crucial that the full prescribed dose (bolus and subsequent infusion) is administered without interruption to ensure sustained reversal of Factor Xa inhibition and control of bleeding. Each 200 mg vial must be reconstituted with 20 mL of Sterile Water for Injection (SWFI) and administered through a 0.2 or 0.22-micron in-line filter.

Safety Alerts

Andexxa carries a Boxed Warning regarding thromboembolic risks, ischemic risks, cardiac arrest, and sudden death. Treatment has been associated with serious and life-threatening adverse events.

• Monitor patients for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest.
• Initiate anticoagulation when medically appropriate to mitigate the risk of thrombosis.

Frequently Asked Questions

What is the Andexxa low-dose regimen?

The low-dose regimen is a 400 mg IV bolus (at 30 mg/min) followed by a 120-minute infusion of 480 mg (at 4 mg/min). It is used for patients on apixaban ≤ 5 mg or rivaroxaban ≤ 10 mg.

When is the Andexxa high-dose regimen indicated?

The high-dose regimen is indicated for patients taking apixaban > 5 mg, rivaroxaban > 10 mg, or if the dose of either inhibitor is unknown. It consists of an 800 mg IV bolus followed by a 960 mg infusion at 8 mg/min for 120 minutes.

What should I do if the patient's Factor Xa inhibitor dose is unknown?

If the last dose of apixaban or rivaroxaban is unknown and the last dose was taken less than 8 hours ago (or time unknown), the high-dose regimen is recommended.

Why does the time since the last anticoagulant dose matter?

The anticoagulant effect of Factor Xa inhibitors diminishes over time. If the last dose was taken 8 or more hours ago, the level of circulating anticoagulant may be low enough that reversal with Andexxa is not required. Clinical judgment is essential in these cases.

How many vials are needed for each regimen?

Andexxa is supplied in 200 mg vials. The low-dose regimen (total 880 mg) requires 5 vials. The high-dose regimen (total 1760 mg) requires 9 vials.

Can Andexxa be used to reverse other anticoagulants like edoxaban or enoxaparin?

Andexxa is specifically approved for the reversal of apixaban and rivaroxaban. It is not approved for the reversal of other Factor Xa inhibitors like edoxaban, betrixaban, or fondaparinux in the United States. Its use for reversing enoxaparin is also not an approved indication.

Are there any special administration requirements?

Yes. After reconstitution, the solution must be administered through a 0.2 or 0.22-micron in-line polyethersulfone (PES) or equivalent low protein-binding filter. Do not mix with other medications.

What are the most serious risks associated with Andexxa treatment?

The most serious risks, as highlighted in the Boxed Warning, are arterial and venous thromboembolic events (e.g., stroke, myocardial infarction, DVT, PE), ischemic events, cardiac arrest, and sudden death.

References

• ANDEXXA® (andexanet alfa) Prescribing Information. Portola Pharmaceuticals, Inc.
• Drugs@FDA: ANDEXXA FDA Approval Information.
• Ondexxya (andexanet alfa) Summary of Product Characteristics. European Medicines Agency.
• Connolly, S. J., et al. (2019). Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. New England Journal of Medicine, 380(14), 1326–1335.