Factor Xa (recombinant), inactivated-zhzo (monograph)

Factor Xa (recombinant), inactivated-zhzo (monograph)

Factor Xa (recombinant), inactivated-zhzo (monograph)

warning

Thromboembolische Risiken, ischämische Risiken, Herzstillstand und plötzlicher Tod

• Treatment with factor [MI and ischemic stroke]cardiac arrest, sudden death).

• Monitor for manifestations of thromboembolic events and initiate anticoagulation if medically appropriate.

• Be alert for signs and symptoms that precede cardiac arrest and provide appropriate medical treatment. (See Thromboembolic Risks, Ischemic Risks, Cardiac Arrest, and Sudden Death under Precautions.)

introduction

Used for factor Xa (recombinant), inactivated-zhzo

Reversal of apixaban or rivaroxaban anticoagulation

Used to reverse apixaban or rivaroxaban anticoagulation in patients with life-threatening or uncontrolled bleeding; For this purpose, it has been designated as an orphan drug by the FDA.

Accelerated approval is based on change from baseline in anti-factor Xa activity following administration to healthy subjects; Improvement in hemostasis not proven. Further FDA approval of this indication may depend on results of studies demonstrating improvement in hemostasis.

Rapidly reverses the anticoagulant effects of apixaban or rivaroxaban (as measured by anti-factor Xa activity, unbound anticoagulant concentration, and thrombin formation).

Not indicated for the treatment of bleeding associated with other factor Xa inhibitors; Safety and effectiveness not proven.

Treatment of bleeding complications in patients receiving direct oral anticoagulants (DOACs) should be individualized based on the severity and location of the bleeding. Antidotes should generally be reserved for patients with severe and life-threatening bleeding. Experts caution that reversal agents should only be administered if clinically relevant DOAC concentrations are documented or expected. If an antidote is required in patients with rivaroxaban- or apixaban-associated severe bleeding, factor Xa (recombinant), inactivated Zhzo, may be used.

Factor Xa (recombinant), inactivated-zhzo dosage and administration

Administration

IV administration

Administer as a direct IV injection (“bolus”) followed by continuous infusion.

Begin continuous infusion within 2 minutes of direct intravenous injection of the drug.

Restoration

Reconstitute vials with 200 mg factor/mL.

Gently swirl (do not shake) vials to facilitate reconstitution (typical dissolution time for each vial is 3-5 minutes).

Reconstitute all required vials for one dose sequentially to shorten overall reconstitution time.

Direct IV Injection: Transfer the appropriate volume of solution from the reconstituted vial(s) to an empty polyolefin or PVC IV bag (≤250 mL) using a 60 mL (or larger) syringe and a 20-gauge (or larger) needle. ).

Continuous IV infusion: Transfer the appropriate volume of solution from the reconstituted vial(s) into an empty polyolefin or PVC IV bag (≤250 mL) using more than a 40 to 60 mL syringe or equivalent 100 mL syringe with a 20-gauge (or larger) needle.

Administer drug IV using a 0.2 or 0.22 μm in-line polyethersulfone filter or equivalent low protein binding filter.

Board of Directors

Direct IV injection: target rate 30 mg/minute.

Continuous IV infusion, low-dose regimen: 4 mg/minute.

High dose continuous IV infusion: 8 mg/minute.

dosage

Adult

Reversal of apixaban or rivaroxaban anticoagulation

IV

Dosing is based on the specific factor Xa inhibitor, the dosage of the factor Xa inhibitor, and the time since the patient's last dose of the factor Xa inhibitor. (See Table 1.)

Table 1. Dosage of factor

Low-dose regimen: Direct IV injection of 400 mg, followed by a continuous IV infusion of 4 mg/minute within 2 minutes for up to 120 minutes (480 mg).

High-dose regimen: Direct IV injection of 800 mg, followed by a continuous IV infusion of 8 mg/minute within 2 minutes for up to 120 minutes (960 mg).

Safety and effectiveness of additional doses of factor Xa (recombinant), inactivated-zhzo, not established.

Resume anticoagulant therapy as soon as medically appropriate.

Special populations

Renal dysfunction

No specific dosage recommendations.

Liver dysfunction

No specific dosage recommendations.

Precautions for Factor Xa (recombinant), inactivated-zhzo

Contraindications

• The manufacturer does not specify any.

Warnings/Precautions

Warnings

Thromboembolic risks, ischemic risks, cardiac arrest and sudden death

Life-threatening thromboembolic and ischemic complications, including sudden death, have been reported. (See warning notice.)

Safety has not been established in patients who have experienced a thromboembolic event or disseminated intravascular coagulation (DIC) within 2 weeks before the life-threatening bleeding event.

Safety has not been established in patients who received prothrombin complex concentrates, recombinant factor VIIa, or whole blood products within 7 days before the bleeding event.

Monitor patients for manifestations of arterial and venous thromboembolic events, ischemic events, and cardiac arrest. Initiate anticoagulation if medically necessary. Provide appropriate treatment for cardiac arrest if necessary.

Reversal of the effect of factor Xa inhibitor therapy increases the risk of thromboembolic events; Restart anticoagulant therapy as soon as medically appropriate after treatment with factor

Further warnings and precautions

Reinstatement or incomplete reversal of anti-factor Xa activity

A rapid and significant decrease in anti-factor Xa activity was observed corresponding to a direct intravenous (“bolus”) injection dose of the drug. This decline continued throughout continuous intravenous infusion of the drug; Anti-factor Xa activity returned to placebo concentrations approximately 2 hours after completion of a direct IV injection or continuous IV infusion. Thereafter, anti-factor Xa activity decreased at a rate similar to the clearance of the factor Xa inhibitor. Tissue factor pathway inhibitor (TFPI) activity in plasma returned to pretreatment levels approximately 96 hours after administration of inactivated factor Xa (recombinant)-zhzo.

Safety and effectiveness of repeated doses of factor Xa (recombinant), inactivated-zhzo, not established.

Impairment of the effect of heparin

May impair the anticoagulant effect of heparin. (See “Specific Medications” under “Interactions.”)

Immunogenicity

Potential for immunogenicity using all therapeutic proteins, including Factor Xa (recombinant), inactivated Zhzo. In patients receiving the drug (1st generation product), low titers of anti-factor. None of these inactivated anti-factor Xa antibodies (recombinant)-zhzo had a neutralizing effect. Development of antibodies that cross-react with factor X or factor Xa was not observed.

Specific populations

pregnancy

No adequate and well-controlled studies in pregnant women. Studies on animal reproduction and development are lacking. Safety and effectiveness during labor and delivery not established.

lactation

It is not known whether factor Xa (recombinant), inactivated-zhzo, is excreted in breast milk. Consider the benefits of breastfeeding and the clinical need for factor

Pediatric use

Safety and effectiveness not proven.

Geriatric use

No overall differences in efficacy or safety between geriatric and younger patients; However, increased sensitivity in some older people cannot be ruled out.

Common side effects

Patients with heavy bleeding: urinary tract infections, pneumonia.

Healthy people: Infusion-related reactions (e.g. feeling hot, flushing, cough, taste disturbance, shortness of breath).

Interactions with other medications

Specific medications

Factor Xa (recombinant), inactivated zhzo pharmacokinetics

Differences in manufacturing processes resulted in a Generation 1 and Generation 2 drug. These products come from the same cell line and the FDA has determined the two products to be bioequivalent.

absorption

beginning

Reduces anti-factor Xa activity quickly (within 2-5 minutes).

distribution

extent

It is not known whether it passes into milk.

Elimination

Half-life

Low dose regimen (1st generation product): 4.3 hours (range: 3.3-11.9 hours).

Low dose regimen (2nd generation product): 3.3 hours (range 2.3-4 hours).

High-dose regimen (1st generation product): 4 hours (range 2-5.7 hours).

High-dose regimen (2nd generation product): 2.7 hours (range 1.9-3.4 hours).

stability

storage

Parenteral

Powder for injection, unopened vial: 2-8°C; do not freeze.

Reconstituted drug solution in vials: Stable at room temperature for ≤8 hours or at 2-8°C for ≤24 hours.

Reconstituted drug solution in infusion bags: Stable for ≤8 hours at room temperature.

Actions

• Recombinant modified human factor Xa protein; Decoy protein that binds and binds to factor

• Has a similar affinity for factor Xa inhibitors as native factor The drug is unable to cleave and activate prothrombin and cannot assemble into the prothrombinase complex.

• Binds to Tissue Factor Pathway Inhibitor (TFPI), a protein that normally binds to native Factor Xa, and inhibits its activity. Inhibition of TFPI activity may increase thrombin formation initiated by tissue factors.

Advice for patients

• It is important to inform patients that reversal of the effects of factor Xa inhibitor therapy increases the risk of thromboembolic events. Arterial and venous thromboembolic events, including ischemic events, cardiac events and sudden death, were reported within 30 days of factor administration

• It is important for women to tell doctors if they are pregnant, plan to become pregnant, or want to breastfeed.

• It is important to inform physicians about any existing or planned concomitant therapies, including prescription and over-the-counter medications, as well as any comorbidities.

• It is important to inform patients of other important precautionary information. (See Precautions.)

Preparations

Excipients in commercial drug preparations may have clinically significant effects in some individuals; Details can be found on the respective product labeling.

For information about shortages of one or more of these drugs, visit the ASHP Drug Shortages Resource Center.

Factor Xa (recombinant), inactivated-zhzo

AHFS DI Essentials™. © Copyright 2024, Selected changes December 13, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Reload page with included references