Version May 2024
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.
Life-threatening bleeding associated with factor Xa inhibitors: Note: Generally used for life-threatening bleeding or bleeding into a critical organ that is not controlled with maximal supportive measures (eg, activated charcoal [if ingestion is within ~2 to 4 hours], antifibrinolytic agent) (Ref).
Life-threatening bleeding associated with edoxaban or betrixaban (off-label use): IV: 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 (Ref).
Life-threatening bleeding associated with apixaban or rivaroxaban: Note: Safety and efficacy of >1 dose of andexanet alfa has not been established. Resume anticoagulant therapy as soon as medically appropriate following treatment.
IV:
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 | |||
|---|---|---|---|
|
Factor Xa Inhibitor |
Factor Xa Inhibitor Last Dose |
Timing of Factor Xa Inhibitor Last Dose Before Andexanet alfa Initiation | |
|
<8 Hours or Unknown |
≥8 Hours | ||
|
Apixaban |
≤5 mg |
Low dose |
Low dose |
|
>5 mg or unknown |
High dose | ||
|
Rivaroxaban |
≤10 mg |
Low dose | |
|
>10 mg or unknown |
High dose | ||
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
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
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Anti-factor Xa activity re-elevation: There is a rapid and substantial decrease in anti-factor Xa activity corresponding to the bolus dose, which is sustained during the continuous infusion. Anti-factor Xa activity returns to levels seen in patients receiving placebo ~2 hours after completion of bolus or continuous infusion; thereafter, anti-factor Xa activity decreases at a rate similar to the clearance of factor Xa inhibitors.
• Thromboembolic and ischemic risks: Arterial and venous thromboembolic events, ischemic events, and cardiac events (including sudden death) were observed within 3 to 30 days postadministration (median time to first event: 7 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous [preservative free]:
Andexxa: 200 mg (1 ea) [latex free; contains polysorbate 80]
Andexxa: 200 mg (1 ea [DSC]) [contains polysorbate 80]
No
Solution (reconstituted) (Andexxa Intravenous)
200 mg (per each): $3,000.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
Life-threatening bleeding associated with apixaban or rivaroxaban: Reversal of anticoagulation in patients treated with apixaban or rivaroxaban experiencing life-threatening or uncontrolled bleeding.
Life-threatening bleeding associated with edoxaban or betrixaban
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Heparin: Andexanet Alfa (Coagulation Factor Xa [Recombinant], Inactivated) may diminish the therapeutic effect of Heparin. Risk X: Avoid combination
Animal reproduction studies have not been conducted.
It is not known if andexanet alfa is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
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-factor Xa activity individually calibrated to each specific factor Xa inhibitor (undetectable anti-factor Xa activity likely excludes clinically relevant drug concentrations). An anti-factor 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 2020]; AHA [Raval 2017]).
Andexanet alfa binds and sequesters the factor Xa inhibitors rivaroxaban and apixaban. In addition, andexanet alfa inhibits the activity of Tissue Factor Pathway Inhibitor, increasing tissue factor-initiated thrombin generation.
Onset: Rapid (Lu 2013)
Distribution: Vss:
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
Half-life elimination: Note: Clinical trials have shown that when andexanet alfa is administered to patients taking apixaban or rivaroxaban, anti-factor Xa activity increases to levels seen in patients receiving placebo ~2 hours after completion of the infusion (Connolly 2016; Siegal 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.
Pharmacokinetic half-life:
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).
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