RfXa Inhibitor Antidote

RfXa Inhibitor Antidote Uses, Dosage, Side Effects, Food Interaction and all others data.

RfXa Inhibitor Antidote is a recombinant human coagulation Factor Xa that promotes blood coagulation. It was developed by Portola Pharmaceuticals and was approved in in May 2018. It is marketed as Andexxa for intravenous injection or infusion and is indicated for the reversal of anticoagulation in combination with rivaroxaban and apixaban in cases of life-threatening or uncontrolled bleeding. Rivaroxaban and apixaban are Factor Xa inhibitors that promote anticoagulation in situations where blood clotting is unfavourable, such as in deep vein thrombosis and pulmonary embolism. However, the use of these agents is associated with a risk for uncontrollable bleeding episodes that can lead to can cause serious or fatal bleeding. RfXa Inhibitor Antidote is currently under regulatory review by the European Union and is undergoing clinical development in Japan .

RfXa Inhibitor Antidote works by binding to Factor Xa inhibitors and prevent them from interacting with endogenous Factor Xa. It displayed high affinity (0.53–1.53 nmol/L) to apixaban, betrixaban, edoxaban and rivaroxaban . However, the effectiveness of andexanet alfa on treating bleeding related to any FXa inhibitors other than apixaban and rivaroxaban was not demonstrated, thus such use is limited . Its pharmacokinetic properties are not reported to be affected by factor Xa inhibitors . RfXa Inhibitor Antidote retains the structural similarity to that of endogenous human factor Xa, but exists in its mature functional form without the need for activation via the intrinsic or extrinsic coagulation pathways and remains catalytically inactive due to structural modification . The procoagulation potential of andexanet alfa is eliminated through the removal of a 34-residue fragment containing Gla: via this truncation, andexanet alfa is unable to bind to membrane surfaces and assemble the prothrombinase complex . It also prevents andexanet alfa from taking up space on phospholipid surface membranes, so that native FXa may bind and assemble the prothrominase complex . The amino acid residue modification from serine to alanine in the binding site of the catalytic domain allows more effective binding to FXa inhibitors and deters the andexanet alfa from converting prothrombin to thrombin .

In vitro, andexanet alfa was shown to dose-dependently reverse the activity of apixaban, betrixaban, edoxaban, rivaroxaban, enoxaparin and fondaparinux on Factor Xa in human and rat plasma .

RfXa Inhibitor Antidote
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Trade Name	RfXa Inhibitor Antidote
Generic	Andexanet alfa
Andexanet alfa Other Names	Andexanet alfa, r-Antidote, rfXa Inhibitor Antidote
Type
Protein binding	No information available.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

RfXa Inhibitor Antidote is a recombinant Factor Xa used to reverse anticoagulation caused by rivaroxaban and apixaban.

RfXa Inhibitor Antidote is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding . Andexxa has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any Factor Xa inhibitors other than apixaban and rivaroxaban .

RfXa Inhibitor Antidote is also used to associated treatment for these conditions: Severe Life-threatening, uncontrollable Bleeding

How RfXa Inhibitor Antidote works

Factor Xa inhibitors promote anticoagulation by binding to both free Factor Xa in plasma and Factor Xa attached to the prothrombinase complex. This ultimately leads to the blockade of thrombin generation or clot formation . RfXa Inhibitor Antidote is a factor Xa decoy that binds to factor Xa inhibitors such as apixaban and rivaroxaban with high affinity and prevents them from binding to endogenous factor Xa. It was also shown to sequester factor Xa inhibitors, leading to reversing their anticoagulant effects and restoring the activity of endogenous factor Xa . RfXa Inhibitor Antidote may also achieve procoagulation via binding and inhibiting the activity of Tissue Factor Pathway Inhibitor (TFPI), which is an endogenous inhibitor of Factor Xa . Inhibition of TFPI by andexanet alfa resulted in a transient increase in the level of prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer . Subsequently, this may result in increased tissue factor-initiated thrombin generation . Since it is a genetically modified variant of human factor Xa, andexanet alfa is not able to cleave and activate prothrombin nor assemble into the prothrombinase complex .