![]() ![]() ![]() Due to the reversible binding of andexanet alfa to the FXa inhibitor, the high sample dilution currently used in commercial clinical assays promotes dissociation of the inhibitor from andexanet alfa, resulting in detection of erroneously elevated anti-FXa activity levels, thereby causing a substantial underestimation of the reversal activity of andexanet alfa. Therapeutic MonitoringĬurrent commercial clinical anti-FXa-activity assays are unsuitable for measuring FXa activity following administration of andexanet alfa. Laboratory assessment of coagulation does not necessarily correlate with or predict the hemostatic effectiveness of andexanet alfa. 12 CLINICAL PHARMACOLOGY, 12.1 Mechanism of Action, 12.2 Pharmacodynamics, 12.3 Pharmacokinetics, 13 NONCLINICAL TOXICOLOGY, 13.1 Carcinogenesis. 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. Andexxa is a modified form of human Factor Xa which works by acting as a decoy that binds to factor Xa (FXa) inhibitors. 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. ![]()
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