FDA New Drug and Biologic Approvals, 2018 Midyear Review

Mary L Windle, PharmD

Disclosures

August 01, 2018

In This Article

Anticoagulation Reversal: AndexXa (coagulation factor Xa, recombinant, inactivated-zhzo)

Indication: Indicated for adults treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding.

Mechanism: Exerts 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.

Dosage:

There are 2 dosage regimens (low dose or high dose) to choose from, as follows:

  • Low dose: 400 mg IV bolus administered at target rate of 30 mg/min; followed by 4 mg/min IV for up to 120 min

  • High dose: 800 mg IV bolus administered at target rate of 30 mg/min; followed by 8 mg/min IV for up to 120 min

Dose based on rivaroxaban or apixaban dose.

Use low dose described above for the following:

  • 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 for the following:

  • 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)

Approval was based on data from two phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban in healthy older volunteers. Results demonstrated a rapid and significant reversal of anti-factor Xa (FXa) activity. Anti-FXa activity was reduced in apixaban-treated participants by 94%, as compared to 21% for placebo (P<0.001). A 92% reduction of anti-FXa activity was observed in the rivaroxaban-treated participants, as compared to 18% for placebo (P<0.001).

In the ANNEXA-4 trial, 67 patients who had acute major bleeding within 18 hr after administration of an FXa inhibitor received coagulation factor Xa recombinant. After the IV bolus plus 2 hour IV infusion, the median anti-FXa activity decreased by 89% from baseline in patients receiving rivaroxaban and by 93% in patients receiving apixaban. Assessment at 12 hours after the infusion adjudicated clinical hemostasis as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI: 64-89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up.

References:

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