Medically reviewed by Drugs.com. Last updated on Feb 25, 2019.
(an DEX a net AL fa)
- Coagulation Factor Xa (Recombinant), Inactivated zhzo
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Andexxa: 100 mg (1 ea); 200 mg (1 ea) [contains polysorbate 80]
Brand Names: U.S.
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.
Generation 1 product: Low dose: 5.1 (range: 3.2 to 13.8) L; High dose: 4.1 (range: 2.4 to 5.7) L
Generation 2 product: Low dose: 4.4 (range: 3.3 to 5.7) L; High dose: 3 (range 2.2 to 5) L
Onset of Action
Rapid (Lu 2013)
Note: Clinical trials have shown that when andexanet alfa is administered to patients taking apixaban or rivaroxaban, anti-factor Xa activity increases to placebo levels ~2 hours after completion of the infusion (Connolly 2016; Siegel 2015). However, elevation of tissue factor-initiated thrombin generation above pretreatment baseline occurs within 2 minutes after administration and is sustained above placebo for at least 22 hours after administration.
Generation 1 product: Low dose: 4.3 (range: 3.3 to 11.9) hours; High dose: 4 (range: 2 to 5.7) hours
Generation 2 product: Low dose: 3.3 (range: 2.3 to 4) hours; High dose: 2.7 (range: 1.9 to 3.4) hours
Pharmacodynamic half-life: ~1 hour (Siegal 2015).
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
Off Label Uses
Reversal of anticoagulation from direct and indirect factor Xa inhibitors
Data from a limited number of patients suggest that andexanet alfa may be beneficial for the reversal of anticoagulation from the factor Xa inhibitor direct oral anticoagulants (DOAC) edoxaban and betrixaban [Crowther 2016], [Crowther 2014]. Andexanet alfa may also be beneficial for the reversal of anticoagulation from enoxaparin, an indirect factor Xa inhibitor [Connolly 2016].
Clinical experience also suggests the utility of andexanet alfa for reversal of factor Xa inhibitor DOACs and enoxaparin [Garcia 2018]. Specific dosing for this off-label use has not been established at this time.
There are no contraindications listed in the manufacturer's labeling.
Reversal of anticoagulation from apixaban or rivaroxaban: IV: Note: Some experts recommend administration of andexanet alfa for life-threatening bleeding when use of a factor Xa inhibitor DOAC (eg, apixaban, rivaroxaban, edoxaban [off-label], betrixaban [off-label]) is confirmed and only after other hemostatic measures (eg, antifibrinolytic therapy [eg, tranexamic acid or aminocaproic acid] and drug removal with activated charcoal) have been shown to be ineffective or when patients are at imminent risk of death from bleeding (used in conjunction with other hemostatic measures) or for those who are in need of emergent surgery (Garcia 2018).
Andexanet alfa dosing regimens: Note: The andexanet alfa dosing regimen (low dose or high dose) is based on the specific factor Xa inhibitor given, the factor Xa 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.
Low dose: 400 mg IV bolus administered at a rate of ~30 mg/minute, followed within 2 minutes by an IV infusion of 4 mg/minute for up to 120 minutes
High dose: 800 mg IV bolus administered at a rate of ~30 mg/minute, followed within 2 minutes by an IV infusion of 8 mg/minute for up to 120 minutes
Andexanet alfa Dose Based on Apixaban or Rivaroxaban Dose
FXa Inhibitor Last Dose
Timing of FXa Inhibitor Last Dose Before Andexanet alfa Initiation
<8 Hours or Unknown
>5 mg or unknown
>10 mg or unknown
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 or unknown before andexanet alfa initiation, then use low dose.
If apixaban dose was >5 mg or unknown and administered <8 hours or 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 or unknown before andexanet alfa initiation, then use low dose.
If rivaroxaban dose was >10 mg or unknown and administered <8 hours or unknown before andexanet alfa initiation, then use high dose.
If rivaroxaban was administered ≥8 hours before andexanet alfa initiation, then use low dose.
Refer to adult dosing.
Note: Reconstitute the number of vials needed based on the vial concentration and dose requirements:
100 mg vial:
Low dose = 4 vials for bolus dose + 5 vials for infusion dose (total number of vials = 9)
High dose = 8 vials for bolus dose + 10 vials for infusion dose (total number of vials = 18)
200 mg vial:
Low dose = 2 vials for bolus dose + 3 vials for infusion dose (total number of vials = 5)
High dose = 4 vials for bolus dose + 5 vials for infusion dose (total number of vials = 9)
To reduce the total reconstitution time, reconstitute all required vials in succession.
Reconstitute each 100 mg vial with 10 mL SWFI or each 200 mg vial with 20 mL SWFI using a ≥20 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 to 5 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.
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.
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. Discard any unused portion.
There are no known significant interactions.
Immunologic: Antibody development (6% to 17%)
Miscellaneous: Infusion related reaction (18%)
1% to 10%:
Cardiovascular: Deep vein thrombosis (6%), ischemic stroke (5%), acute myocardial infarction (3%), pulmonary embolism (3%), cardiogenic shock (2%), cardiac failure (1%)
Genitourinary: Urinary tract infection (≥5%)
Respiratory: Pneumonia (≥5%), acute respiratory failure (1%)
Frequency not defined: Cardiovascular: Arterial thromboembolism, venous thromboembolism
<1%, postmarketing, and/or case reports: Coronary thrombosis, intracardiac thrombus, nonsustained ventricular tachycardia
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, which is sustained during the continuous infusion. Anti-FXa activity returns to placebo levels ~2 hours after completion of bolus or continuous infusion; thereafter, 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.
Signs/symptoms of arterial and venous thromboembolic events, ischemic events, or cardiac arrest
Signs/symptoms of hemostasis; if available, the preferred test to rule out clinically significant serum concentrations and quantify anticoagulant effect is anti-Xa activity individually calibrated to each specific factor Xa inhibitor (undetectable anti-Xa activity likely excludes clinically relevant drug concentrations). An anti-Xa activity assay calibrated for low molecular weight heparin can rule out clinically relevant drug concentrations of a factor Xa inhibitor DOAC, but is not useful for quantification (ACC [Tomaselli 2017]; AHA [Raval 2017]).
Animal reproduction studies have not been conducted.
• 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.
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- Drug class: anticoagulant reversal agents
- Coagulation factor Xa
- Andexanet Alfa
- Coagulation factor xa recombinant, inactivated-zhzo Intravenous (Advanced Reading)
Other brands: Andexxa