Andexxa

— THERAPEUTIC CATEGORIES —
  • Bleeding disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Andexxa Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Coagulation factor Xa (recombinant), inactivated-zhzo 100mg; per vial; lyophilized pwd for IV inj after reconstitution; preservative-free.

    Pharmacological Class

    Factor Xa (recombinant).

    How Supplied

    Single-use vials—4

    How Supplied

    Andexxa (coagulation factor Xa (recombinant), inactivated-zhzo) is a white to off-white lyophilized cake or powder supplied as 4 single-use vials in a carton; each vial contains 200mg of Andexxa and is not made with natural rubber latex.

    Storage

    Unopened vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze.

    Manufacturer

    Portola Pharmaceuticals

    Generic Availability

    NO

    Andexxa Indications

    Indications

    Reversal of anticoagulation with rivaroxaban or apixaban due to life-threatening or uncontrolled bleeding.

    Limitations of Use

    Not effective for, and not indicated for, the treatment of bleeding related to any FXa inhibitors other than apixaban and rivaroxaban.

    Andexxa Dosage and Administration

    Adult

    For IV use only. Low-dose regimen: initially 400mg (target rate: 30mg/min) as IV bolus, followed by 4mg/min IV infusion for up to 120mins. High-dose regimen: initially 800mg (target rate: 30mg/min) as IV bolus, followed by 8mg/min IV infusion for up to 120mins. If last rivaroxaban dose ≤10mg or apixaban dose ≤5mg given <8hrs (or unknown): use low-dose regimen. If last rivaroxaban dose >10mg/unknown or apixaban dose >5mg/unknown given <8hrs (or unknown): use high-dose regimen. If rivaroxaban or apixaban dose given ≥8hrs: use high-dose regimen.

    Children

    Not studied.

    Andexxa Contraindications

    Not Applicable

    Andexxa Boxed Warnings

    Boxed Warning

    Thromboembolic risks. Ischemic risks. Cardiac arrests. Sudden deaths.

    Boxed Warning

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

    • Andexxa 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

      • Sudden deaths

    • Monitor for thromboembolic events and initiate anticoagulation when appropriate.

    • Monitor for signs and symptoms that precede cardiac arrest and provide treatment as needed.

    Andexxa Warnings/Precautions

    Warnings/Precautions

    Risk of serious events (eg, thromboembolism, ischemia, cardiac arrest, sudden deaths); monitor for signs/symptoms; resume anticoagulant therapy as soon as medically appropriate after Andexxa. Re-elevation or incomplete reversal of anti-FXa activity can occur. Labor & delivery: not evaluated. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Thromboembolic and Ischemic Risks

    • Monitor for signs and symptoms of arterial and venous thromboembolic events, ischemic events, and cardiac arrest.

    • Following treatment with Andexxa, resume anticoagulant therapy as soon as possible to reduce thromboembolic risk.

    • The safety of Andexxa has not been evaluated in patients who experienced thromboembolic events or disseminated intravascular coagulation within 2 weeks prior to the life-threatening bleeding event requiring treatment with Andexxa.

    • The safety of Andexxa has not been evaluated in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within seven days prior to the bleeding event.

    Re-elevation or Incomplete Reversal of Anti-FXa Activity

    • The time course of anti-FXa activity following Andexxa administration was consistent among healthy volunteer studies and the ANNEXA-4 study in bleeding patients.

    • There was a rapid and substantial decrease in anti-FXa activity corresponding to the Andexxa bolus from baseline, and this was sustained through the end of the continuous infusion. Approximately 2 hours after completion of bolus or continuous infusion, anti-FXa activity returned to the placebo levels.

    Use of Heparin Following Administration of Andexxa

    • May interfere with the anticoagulant effect of heparin.

    • Using Andexxa as an antidote for heparin has not been established.

    • Prior to heparinization, avoid use of Andexxa for the reversal of direct FXa inhibitors (apixaban and rivaroxaban). Use an alternative anticoagulant to heparin if anticoagulation is needed.

    Pregnancy Considerations

    Risk Summary

    • There are no adequate and well-controlled studies of Andexxa in pregnant women to inform patients of associated risks.

    • Labor or Delivery: The safety and efficacy of Andexxa has not been evaluated.

    Nursing Mother Considerations

    Risk Summary

    • There is no information regarding the presence of Andexxa in human milk, the effects on the breastfed child, or the effects on milk production.

    • Consider the mother’s clinical need and any potential adverse effects on the breastfed child from Andexxa or from the underlying maternal condition.

    Pediatric Considerations

    Safety and efficacy has not been studied.

    Geriatric Considerations

    No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between elderly and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out.

    Andexxa Pharmacokinetics

    Elimination

    Half-life: 3.3 hours (low-dose), 2.7 hours (high-dose).

    Andexxa Interactions

    Andexxa Adverse Reactions

    Adverse Reactions

    Urinary tract infections, pneumonia, infusion-related reactions.

    Andexxa Clinical Trials

    Clinical Trials

    The approval of Andexxa was based on two phase 3 studies (Study 1 ANNEXA-A; Study 2 ANNEXA-R), which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of rivaroxaban and apixaban in healthy participants. Both studies evaluated the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion.

    In addition, the FDA reviewed interim data from  a single-arm, open-label study (Study 3 ANNEXA-4) in patients with major bleeding and who have recently received an FXa inhibitor. This study evaluated the percent change in anti-FXa activity from baseline to the nadir between 5 minutes after the end of the bolus up until the end of the infusion and the rate of effective hemostasis within 12 hours after infusion.

    In Study 1 and 2, results showed that Andexxa quickly and significantly reversed anti-Factor Xa activity. In Study 1, the mean percent change in anti-FXa activity from baseline at the nadir was -92.3% for Andexxa vs -32.7% for placebo (difference -59.5%; 95% CI, -64.1, -55.2; P <.0001). In Study 2, the mean percent change in anti-FXa activity from baseline at the nadir was -96.7% for Andexxa vs -44.6% for placebo (difference -51.9%; 95% CI, -58.0, -47.0; P <.0001). 

    In Study 3, the median decrease in anti-FXa activity from baseline to nadir for apixaban was -93% with a 95% CI of (-94%; -92%) and for rivaroxaban was -93% with a 95% CI of (-94%; -90%). An improvement in hemostasis has not been established. Andexxa has not been shown to be effective for bleeding related to any FXa inhibitors other than apixaban or rivaroxaban.

    Andexxa Note

    Not Applicable

    Andexxa Patient Counseling

    Patient Counseling

    Inform patients that reversing FXa inhibitor therapy increases the risk of thromboembolic events. Arterial and venous thromboembolic events, ischemic events, cardiac events, and sudden death were observed within 30 days following Andexxa administration.

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