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Andexanet Alfa

Medically reviewed on August 12, 2018

Pronunciation

(an DEX a net AL fa)

Index Terms

  • Coagulation Factor Xa (Recombinant), Inactivated zhzo
  • PRT064445

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Andexxa: 100 mg (1 ea) [contains polysorbate 80]

Brand Names: U.S.

  • Andexxa

Pharmacologic Category

  • Antidote

Pharmacology

Andexanet alfa binds and sequesters the FXa inhibitors rivaroxaban and apixaban. In addition, andexanet alfa inhibits the activity of Tissue Factor Pathway Inhibitor (TFPI), increasing tissue factor-initiated thrombin generation.

Distribution

Vd: 5 L

Onset of Action

Rapid (Lu 2013)

Half-Life Elimination

5 to 7 hours

Use: Labeled Indications

Reversal of anticoagulation from apixaban or rivaroxaban: Reversal of anticoagulation in patients treated with apixaban or rivaroxaban experiencing life-threatening or uncontrolled bleeding

Limitation of use: Andexanet alfa has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any Factor Xa (FXa) inhibitors other than apixaban and rivaroxaban.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Reversal of anticoagulation from apixaban or rivaroxaban: IV: Note: The andexanet alfa dosing regimen (low dose or high dose) is based on the specific FXa inhibitor given, the FXa inhibitor dose, and time since it was last taken. Safety and efficacy of >1 dose of andexanet alfa has not been established. Resume anticoagulant therapy as soon as medically appropriate following treatment.

Andexanet alfa Dose Based on Apixaban or Rivaroxaban Dose

FXa inhibitor

FXa inhibitor last dose

Timing of FXa Inhibitor Last Dose Before Andexanet alfa Initiation

<8 Hours or Unknown

≥8 Hours

Apixaban

≤5 mg

Low dose

Low dose

>5 mg/unknown

High dose

Rivaroxaban

≤10 mg

Low dose

>10 mg/unknown

High dose

Table has been converted to the following text.

Andexanet alfa Dose Based on Apixaban or Rivaroxaban Dose:

If apixaban dose was ≤5 mg and administered <8 hours/unknown before andexanet alfa initiation, then use low dose.

If apixaban dose was >5 mg/unknown and administered <8 hours/unknown before andexanet alfa initiation, then use high dose.

If apixaban was administered ≥8 hours before andexanet alfa initiation, then use low dose.

If rivaroxaban dose was ≤10 mg and administered <8 hours/unknown before andexanet alfa initiation, then use low dose.

If rivaroxaban dose was >10 mg/unknown and administered <8 hours/unknown before andexanet alfa initiation, then use high dose.

If rivaroxaban was administered ≥8 hours before andexanet alfa initiation, then use low dose.

Andexanet alfa Dosing Regimens:

Low dose: 400 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute IV infusion for up to 120 minutes

High dose: 800 mg IV bolus administered at a rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute IV infusion for up to 120 minutes

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Note: Reconstitute the number of vials (100 mg/vial) needed based on the dose requirements: Low dose = 4 vials for bolus dose + 5 vials for infusion dose; High dose = 8 vials for bolus dose + 10 vials for infusion dose. To reduce the total reconstitution time, reconstitute all required vials in succession.

Reconstitute each 100 mg vial with 10 mL SWFI using a 10 mL syringe and ≥20 gauge needle; slowly inject SWFI onto the inside wall of the vial to minimize foaming. Gently swirl vial until complete dissolution of powder. Do not shake. Typical dissolution time ~3 minutes; if dissolution is incomplete, discard vial and do not use. Reconstituted solution contains andexanet alfa at a concentration of 10 mg/mL.

IV bolus: Use a ≥60 mL syringe with a ≥20 gauge needle to withdraw reconstituted solution from the vial and transfer the solution into an empty polyolefin or polyvinyl chloride IV bag with a volume of ≤250 mL.

Continuous IV infusion: Use the same procedure described above. May use more than one 40 to 60 mL syringe or a 100 mL syringe to transfer reconstituted solution to IV bag.

Administration

IV: For IV administration. Initiate bolus at a target rate of ~30 mg/minute. For IV infusion, use of a 0.2 or 0.22 micron in-line polyethersulfone or equivalent low protein-binding filter is required.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Reconstituted vials are stable at room temperature ≤8 hours, or may be stored ≤24 hours at 2°C to 8°C. Reconstituted solution in IV bags is stable at room temperature ≤8 hours, or may be stored ≤16 hours at 2°C to 8°C. Discard any unused portion.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%: Local: Infusion site reaction (18%)

1% to 10%:

Cardiovascular: Deep vein thrombosis (6%), ischemic stroke (5%), acute myocardial infarction (3%), pulmonary embolism (3%), cardiogenic shock (2%), exacerbation of congestive heart failure (1%)

Genitourinary: Urinary tract infection (≥5%)

Respiratory: Pneumonia (≥5%), acute respiratory failure (1%)

<1%, postmarketing, and/or case reports: Antibody development, cerebrovascular accident (embolic), coronary thrombosis, intracardiac thrombus, nonsustained ventricular tachycardia

ALERT: U.S. Boxed Warning

Thromboembolic risks, ischemic risks, cardiac arrest, and sudden deaths:

Treatment with andexanet alfa has been associated with serious and life-threatening adverse events, including: Arterial and venous thromboembolic events, ischemic events (including myocardial infarction and ischemic stroke), cardiac arrest, and sudden deaths. Monitor for thromboembolic events and initiate anticoagulation when medically appropriate. Monitor for symptoms and signs that precede cardiac arrest and provide treatment as needed.

Warnings/Precautions

Concerns related to adverse effects:

• Anti-FXa activity re-elevation: There is a rapid and substantial decrease in anti-FXa activity corresponding to the bolus dose. Following the continuous infusion, anti-FXa activity increases and peaks 4 hours after infusion. Following the peak, anti-FXa activity decreases at a rate similar to the clearance of FXa inhibitors.

• Thromboembolic and ischemic risks: Arterial and venous thromboembolic events, ischemic events, and cardiac events (including sudden death) were observed within 30 days post-administration (median time to first event: 6 days). Monitor patients for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. To reduce thromboembolic risk, resume anticoagulant therapy as soon as medically appropriate following treatment with andexanet alfa. Safety has not been evaluated in patients with thromboembolic events or disseminated intravascular coagulation within 2 weeks prior to the bleeding event or in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within 7 days prior to the bleeding event.

Monitoring Parameters

Signs/symptoms of arterial and venous thromboembolic events, ischemic events, or cardiac arrest

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flushing, sensation of warmth, or change in taste. Have patient report immediately to prescriber signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), persistent cough, severe dizziness, passing out, severe nausea, vomiting, sweating a lot, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), or signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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