coagulation factor Xa recombinant, inactivated-zhzo (Rx)

Brand and Other Names:AndexXa, andexanet alfa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 100mg/single-use vial
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Factor Xa Reversal

Indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding

There are 2 dosage regimens (low dose or high dose) to choose from

Safety and efficacy of an additional dose has not been established

Low or high dose regimens

  • Low dose
    • Initial IV bolus: 400 mg IV; target infusion rate of 30 mg/min
    • Follow-on IV infusion: 4 mg/min IV for up to 120 min
  • High dose
    • Initial IV bolus: 800 mg IV; target infusion rate of 30 mg/min
    • Follow-on IV infusion: 8 mg/min IV for up to 120 min

Dose based on rivaroxaban or apixaban dose

  • Use low dose described above
    • Rivaroxaban dose ≤10 mg (any timing from last dose)
    • Apixaban dose ≤5 mg (any timing from last dose)
    • Rivaroxaban >10 mg or dose unknown (≥8 hr from last dose)
    • Apixaban >5 mg or dose unknown (≥8 hr from last dose)
  • Use high dose described above
    • Rivaroxaban >10 mg or dose unknown (<8 hr from last dose or unknown)
    • Apixaban >5 mg or dose unknown (<8 hr from last dose or unknown)

Dosing Considerations

Accelerated approval

  • Approved under accelerated approval based on the change from baseline in anti-FXa activity in healthy volunteers
  • An improvement in hemostasis has not been established
  • Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis in patients

Limitation of use

  • Has not been shown effective for, and is not indicated for, treatment of bleeding related to any FXa inhibitors other than apixaban and rivaroxaban

Restarting antithrombotic therapy

  • Patients treated with FXa inhibitor therapy have underlying disease states that predispose them to thromboembolic events, thus reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease
  • To reduce the risk of thrombosis, resume anticoagulant therapy as soon as medically appropriate after dose

Safety and efficacy not established

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Adverse Effects

>10%

Infusion-related reactions (18%)

Thromboembolic events

  • Note: 33% of patients were on antithrombotic therapy at time of event
  • Deep vein thrombosis (33%)
  • Ischemic stroke (24%)
  • Acute myocardial infarction (15%)
  • Pulmonary embolism (15%)

Deaths due to bleeding <30 days postdose

  • 25 deaths (14%)
  • By bleeding type, patient deaths <days 30 postdose
    • Intracranial bleeding (14%)
    • GI bleeding (10%)
    • Other bleeding types (19%)

1-10%

Thromboembolic events

  • Note: 33% of patients were on antithrombotic therapy at time of event
  • Cardiogenic shock (9%)
  • Sudden death (6%)
  • CHF (6%)
  • Acute respiratory failure (6%)
  • Cardiac arrest (3%)
  • Cardiac thrombus (3%)
  • Embolic stroke (3%)
  • Iliac artery thrombosis (3%)
  • Nonsustained ventricular tachycardia (3%)
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Warnings

Black Box Warnings

Serious and life-threatening adverse effects

  • Monitor for thromboembolic events and initiate anticoagulation when medically appropriate
  • Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed
  • Treatment has been associated with the following serious and life-threatening adverse events, including
    • Arterial and venous thromboembolic events
    • Ischemic events, including myocardial infarction and ischemic stroke
    • Cardiac arrest
    • Sudden deaths

Contraindications

None

Cautions

Arterial and venous thromboembolic events, ischemic events, and cardiac events, including sudden death, were observed within 30 days after administration (see Black Box Warnings)

Reelevation or incomplete reversal of anti-FXa activity

  • Compared wtih baseline, the ANNEXA-4 clinical trial observed a rapid and substantial decrease in anti-FXa activity corresponding to the IV bolus that was sustained through the end of the continuous infusion
  • Following the infusion, there was an increase in anti-FXa activity, which peaked 4 hr after infusion
  • After this peak, the antiFXa activity decreased at a rate similar to the clearance of the FXa inhibitors
  • ~50% of patients experience >90% decrease from baseline anti-FXa activity after administration
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Pregnancy

Pregnancy

Data are not available in pregnant women to inform patients of associated risks

Safety during labor and delivery has not been evaluated

Animal reproductive and development studies have not been conducted

Lactation

Data are not available regarding the presence in human milk, the effects on the breastfed child, or the effects on milk production

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Exerts its procoagulant effect by binding and sequestering the FXa inhibitors, rivaroxaban and apixaban

Another observed procoagulant effect is its ability to bind and inhibit the activity of tissue factor pathway inhibitor (TFPI); inhibiting TFPI activity can increase tissue factor-initiated thrombin generation

Distribution

Vd: 5 L; ~equivalent to blood volume

Elimination

Half-life: 5-7 hr

Clearance: 4.3 L/hr

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Administration

IV Preparation

Reconstitution

  • Reconstitute each 100-mg vial using a 10-mL syringe and ≥20-gauge needle
  • Slowly inject 10 mL sterile water for injection; direct solution onto the inside wall of the vial to minimize foaming
  • Resulting concentration is 10 mg/mL
  • To reduce the total reconstitution time needed during preparation, reconstitute all required vials in succession
  • Low dose requires 4 vials for bolus and 5 vials for infusion
  • High dose requires 8 vials for bolus and 10 vials for infusion
  • Ensure dissolution by gently swirling each vial; do not shake (may lead to foaming); typical dissolution time is 3 minutes; discard vial if dissolution is incomplete
  • Upon reconstitution, visually inspect solution for particulate matter and discoloration prior to administration; solution should appear clear, colorless to slightly yellow

IV bolus preparation

  • Use ≥60-mL syringe with ≥20-gauge needle to withdraw the reconstituted solution from each vial until the required dosing volume is achieved
  • Note the total volume withdrawn into the syringe
  • Transfer solution from the syringe into an empty polyolefin or PVC IV bag with a volume of ≤250 mL
  • Discard syringe, needle, and vials, including any unused portion of drug

Continuous IV infusion preparation

  • Follow the same procedure outlined above for reconstitution and IV bolus preparation
  • More than one 40- to 60-mL syringe, or an equivalent 100-mL syringe, may be used for transfer of reconstituted solution to the IV bag

IV Administration

Administer intravenously, using a 0.2- or 0.22-micron in-line polyether sulfone or equivalent low protein-binding filter

Start the bolus at a target rate of ~30 mg/minute

Within 2 minutes following the bolus dose, administer the continuous IV infusion for up to 120 minutes

Storage

Does not contain preservatives

Unopened vials

  • Refrigerate at 2-8°C (36-46°F)
  • Do not freeze

Reconstituted solution

  • In vials
    • Room temperature for up to 8 hr, or
    • Refrigerate at 2-8°C for up to 24 hr
  • In IV bags
    • Room temperature for up to 8 hr, or
    • Refrigerate at 2-8°C for up to 16 hr
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Images

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.