The sustained elevation of thrombin generation over the baseline range and the sustained elevation over placebo were not observed in a contact-activated thrombin generation assay (an assay that is not affected by TF-TFPI interaction). The TF-initiated thrombin generation was elevated above placebo for at least 22 hours. The anti-FXa activity returned to the placebo levels approximately two hours after completion of a bolus or continuous infusion, whereas TFPI activity in plasma returned to the pretreatment levels approximately 96 hours following andexanet alfa administration.Įlevation of TF-initiated thrombin generation above the baseline range (prior to anticoagulation) occurred within two minutes following a bolus administration of andexanet alfa and was maintained throughout the duration of the continuous infusion. Dosing of andexanet alfa, as a bolus followed by a two-hour continuous infusion, resulted in a rapid decrease in anti-FXa activity (within two minutes after the completion of the bolus administration) followed by reduced anti-FXa activity that was maintained throughout the duration of the continuous infusion. The dose and dosing regimen of andexanet alfa that are required to reverse anti-FXa activity and to restore thrombin generation were determined in dose-ranging studies on healthy volunteers. In addition to its ability to sequester the FXa inhibitors, rivaroxaban and apixaban, andexanet alfa has been shown to inhibit TFPI activity. The effects of andexanet alfa can be measured using assays for its anti-FXa activity, free fraction of FXa inhibitor, and thrombin generation. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Anticoagulant reversal for life-threatening bleeds.FDA approved in May 2018, limited availability June 2018 with broader commercial launch in early 2019.Inhibits the activity of the Tissue Factor Pathway Inhibitor (TFPI), increasing tissue factor-initiated thrombin generation.Binds and sequesters factor Xa inhibitors.Dosage Forms: solution reconstituted, 100 mg per vialĪdult Dosing Determined by last dose, type of factor Xa inhibitor, and dose of inhibitorĤ00 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute for up to 120 minutesĨ00 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute for up to 120 minutes.Type: factor Xa inhibitor reversal, antidote.2.1 Determined by last dose, type of factor Xa inhibitor, and dose of inhibitor.

Andexxa mechanism of action