andexanet alfa

Action and Spectrum

Actions and Spectrum: 

Actions: 

The primary way that andexanet alfa, a recombinantly engineered human factor Xa protein, works is by acting as a particular counter-agent for factor Xa inhibitors. Anticoagulant drugs known as factor Xa inhibitors function by preventing factor Xa, an essential enzyme in the coagulation cascade, from acting. The purpose of andexanet alfa is to attach to and sequester factor Xa inhibitors, counteracting the anticoagulant effects of these drugs. 

Spectrum: 

Regarding andexanet alfa, its range of action is concentrated in its capacity to counteract factor Xa inhibitors’ anticoagulant effects. Particularly made to counteract the anticoagulant effects of factor Xa inhibitors—drugs like apixaban, rivaroxaban, edoxaban, and enoxaparin—is andexanet alfa. Reversing factor Xa inhibitor-induced anticoagulation is the principal goal of andexanet alfa.

Because it selectively reverses the effects of factor Xa inhibitors without influencing other elements of the coagulation cascade or interfering with other kinds of anticoagulants, andexanet alfa is regarded as a particular antidote for these drugs. The capacity of andexanet alfa to quickly counteract factor Xa inhibitors’ anticoagulant effects is well-known.

This is especially critical in emergency scenarios where prompt restoration of normal coagulation is essential, such as life-threatening bleeding or the necessity for immediate surgery.

Because andexanet alfa’s effectiveness is dose-dependent, the right dosage may differ depending on a number of variables, including the patient’s renal function, the particular factor Xa inhibitor, and the amount and timing of the last dose of the inhibitor. Because andexanet alfa acts quickly, medical professionals may more accurately control the reversal process and the patient’s coagulation status. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

• Deaths from bleeding within 30 days after a dosage: 

25 fatalities (14%). 

patient fatalities according to type of hemorrhage 

Brain hemorrhage (14%). 

GI hemorrhage (10%) 

Other forms of bleeding (19%) 

• Reactions connected to infusion (18%) 
• Events thromboembolic: 

Note: At the time of the occurrence, 33% of patients were receiving antithrombotic treatment. 

Pulmonary embolism (15%) 

Ischemic stroke (24%) 

Deep vein thrombosis (33%) 

Acute myocardial infarction (15%) 

1-10% 

• Events thromboembolic: 

Note: At the time of the occurrence, 33% of patients were receiving antithrombotic treatment. 

Nonsustained ventricular tachycardia (3%) 

Acute respiratory failure (6%) 

Cardiogenic shock (9%) 

CHF (6%) 

Iliac artery thrombosis (3%) 

Cardiac arrest (3%) 

Embolic stroke (3%) 

Cardiac thrombus (3%) 

Sudden death (6%) 

Black Box Warning

Black Box Warning: 

RISKS Associated with thromboembolism, ischemia, cardiac arrest, and sudden deaths: This medication’s side effects have been linked to major, potentially fatal complications such as arterial and venous thromboembolic events, myocardial infarction, ischemic stroke, cardiac arrest, and unexpected deaths.

When prescribed by a physician, start anticoagulation and keep an eye out for thromboembolic episodes. Keep an eye out for warning signs and symptoms of cardiac arrest and administer treatment as necessary. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• ICH with GCS < 7 
• Known allergy response to hamster proteins 
• Hypersensitivity 

Cautions 

• Risks of thromboembolism and ischemia: 

Keep an eye out for symptoms of cardiac arrest, ischemic episodes, and arterial and venous thromboembolic events in patients. 

As soon as it is medically appropriate, return to anticoagulant medication to lower the risk of thromboembolism. treatment 

Patients who had disseminated intravascular coagulation or thromboembolic events two weeks before a life-threatening bleeding event necessitating this drug’s treatment were not included in the safety evaluation. 

Additionally, safety was not assessed in patients who had received whole blood products, recombinant factor VIIa, or prothrombin complex concentrates within seven days of the bleeding incident. 

• Increased or partial inhibition of anti-FXa function: 

The ANNEXA-4 clinical trial showed a significant and quick drop in anti-FXa activity relative to the IV bolus that persisted until the end of the continuous infusion when compared to baseline. 

There was an increase in anti-FXa activity following the infusion, which peaked four hours later. 

Following this peak, the antiFXa activity declined at a pace that was comparable to the FXa inhibitors’ clearance. 

After administration, ~50% of patients have a decrease in anti-FXa activity of >90% from baseline. 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

A recombinant version of the human FXa protein called andexanet alfa has been altered to be devoid of FXa enzyme activity. The protein’s ability to assemble into the prothrombinase complex was eliminated by removing the gamma-carboxyglutamic acid (Gla) domain, which also eliminated any anti-coagulant effects. The substitution of alanine for the serine in the active site rendered the molecule incapable of cleaving and activating prothrombin. 

One such FXa inhibitor reversal medication is andexanet alfa. The binding and sequestration of the FXa inhibitor is the main mode of action. Furthermore, it has been noted that andexanet alfa binds to and inhibits tissue factor pathway inhibitor (TFPI). Tissue factor-initiated thrombin generation can be increased by inhibiting TFPI activity, which has a procoagulant impact. 

Pharmacodynamics: 

Binds and sequesters the FXa inhibitors rivaroxaban and apixaban to exert its procoagulant action.  

Its capacity to bind and inhibit tissue factor pathway inhibitor (TFPI) activity has also been reported to have procoagulant effects; blocking TFPI activity can enhance tissue factor-initiated thrombin production.  

Pharmacokinetics: 

Absorption 

N/A 

Distribution 

The volume of distribution of andexanet alfa is 5 L; equivalent to volume of blood. 

Metabolism 

N/A 

Elimination and Excretion 

The half-life is 5-7 hours 

Clearance is 4.3 L per hour 

Adminstartion

Administration: 

The reconstituted solution (10 mg/mL) is transferred to sterile large volume syringes, if a syringe pump is used for administration, or to appropriate empty intravenous bags made of polyolefin (PO) or polyvinyl chloride (PVC) material, without further dilution, once the required number of vials of Ondexxya have been reconstituted.

A 0.2 or 0.22 micron in-line polyethersulfone (PES) filter, or an equivalent low protein-binding filter, should be employed prior to delivery by IV infusion. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: andexanet alfa 

Pronounced: AN-deks-uh-net AL-fuh 

Why do we use andexanet alfa?  

Specifically, factor Xa inhibitors, which are anticoagulant drugs, can be reversed with andexanet alfa. When the need arises to quickly reverse the anticoagulant effects of factor Xa inhibitors, it acts as a particular counteragent.

While factor Xa inhibitors are frequently used to treat and prevent blood clots, there are some circumstances in which their effects must be promptly reversed, such as during emergency surgery or in cases of life-threatening bleeding. 

An injectable drug called Andexxa (andexanet alfa) is used to treat uncontrollable or potentially fatal bleeding in patients using Xarelto (rivaroxaban) or Eliquis (apixaban), which are anticoagulants (blood thinners). It is usually injected into your vein by a qualified healthcare professional in a hospital or urgent care facility.