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Antihemophilic Factor (recombinant), Glycopegylated-exei

Class: Hemostatics
Chemical Name: Human coagulation factor VIII-(1-750)-(1638-1648)-peptide compound with human coagulation factor VIIIa light chain, glycosylated and pegylated
CAS Number: 1309086-46-1
Brands: Esperoct

Medically reviewed by Drugs.com on Feb 24, 2020. Written by ASHP.

Introduction

Antihemophilic factor (recombinant), glycopegylated-exei is a hemostatic.

Uses for Antihemophilic Factor (recombinant), Glycopegylated-exei

Antihemophilic factor (recombinant), glycopegylated-exei has the following uses:

Antihemophilic factor (recombinant), glycopegylated-exei is a coagulation Factor VIII concentrate indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes; perioperative management of bleeding; and routine prophylaxis to reduce the frequency of bleeding episodes. Antihemophilic factor (recombinant), glycopegylated-exei is not indicated for the treatment of von Willebrand disease.

Antihemophilic Factor (recombinant), Glycopegylated-exei Dosage and Administration

General

Antihemophilic factor (recombinant), glycopegylated-exei is available in the following dosage form(s) and strength(s):

For injection: nominally 500, 1000, 1500, 2000, or 3000 international units (IU or unit), lyophilized powder in single-dose vials for reconstitution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For intravenous infusion after reconstitution only.

Dosage and duration of treatment depend on the severity of the Factor VIII deficiency, on the location and extent of bleeding, and on the patient’s clinical condition. Careful monitoring of replacement therapy is necessary in cases of major surgery or life-threatening bleeding episodes.

Each vial of antihemophilic factor (recombinant), glycopegylated-exei contains the labeled amount of recombinant Factor VIII in international units (IU or unit). One unit of Factor VIII activity corresponds to the quantity of Factor VIII in one milliliter of normal human plasma. The calculation of the required dosage of Factor VIII is based on the empirical finding that one unit of Factor VIII per kg body weight raises the plasma Factor VIII activity by two IU/dL.

Antihemophilic factor (recombinant), glycopegylated-exei may be dosed to achieve a specific target Factor VIII activity level, depending on the severity of hemophilia, for on-demand treatment/control of bleeding episodes or perioperative management. To achieve a specific target Factor VIII activity level, use the following formula:

Dosage (units) = Body Weight (kg) × Desired Factor VIII Increase (units/dL or % normal) × 0.5

Base the dose and frequency of antihemophilic factor (recombinant), glycopegylated-exei on the individual clinical response. Patients may vary in their pharmacokinetic and clinical responses.

If monitoring of Factor VIII activity is performed, use a chromogenic or one-stage clotting assay appropriate for use with antihemophilic factor (recombinant), glycopegylated-exei.

Pediatric Patients

On-Demand Treatment and Control of Bleeding Episodes

The following dosage recommendations can be used as a guide to dose antihemophilic factor (recombinant), glycopegylated-exei for the treatment of bleeding episodes:

Children <12 years of age:

Minor Bleeding (e.g., early hemarthrosis, mild muscle bleeding, or oral bleeding): 65 units/kg. One dose should be sufficient.

Moderate Bleeding (e.g., more extensive hemarthrosis, muscle bleeding, or hematoma): 65 units/kg. An additional dose may be administered after 24 hours.

Major Bleeding (e.g., life- or limb-threatening hemorrhages, GI bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures): 65 units/kg. Additional dose(s) may be administered approximately every 24 hours.

Children ≥12 years of age:

See Adult Dosage.

Perioperative Management of Bleeding

The dose level and dosing intervals for surgery depend on the procedure and local practice.

The following dosage recommendations can be used as a guide to dose antihemophilic factor (recombinant), glycopegylated-exei during surgery:

Children <12 years of age:

Minor surgery (e.g., tooth extraction): 65 units/kg administered preoperatively. Additional dose(s) can be administered after 24 hours if necessary.

Major surgery (e.g., intracranial, intra-abdominal, intrathoracic, or joint replacement surgery): 65 units/kg administered preoperatively. Additional doses can be administered approximately every 24 hours for the first week and then approximately every 48 hours until wound healing has occurred.

Children ≥12 years of age:

See Adult Dosage.

Routine Prophylaxis
Children <12 years of age:

65 units/kg twice weekly. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.

Children ≥12 years of age:

See Adult Dosage.

Adults

On-Demand Treatment and Control of Bleeding Episodes

The following dosage recommendations can be used as a guide to dose antihemophilic factor (recombinant), glycopegylated-exei for the treatment of bleeding episodes:

Minor Bleeding (e.g., early hemarthrosis, mild muscle bleeding, or oral bleeding): 40 units/kg. One dose should be sufficient.

Moderate Bleeding (e.g., more extensive hemarthrosis, muscle bleeding, or hematoma): 40 units/kg. An additional dose may be administered after 24 hours.

Major Bleeding (e.g., life- or limb-threatening hemorrhages, GI bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures): 50 units/kg. Additional dose(s) may be administered approximately every 24 hours.

Perioperative Management

The dose level and dosing intervals for surgery depend on the procedure and local practice.

The following dosage recommendations can be used as a guide to dose antihemophilic factor (recombinant), glycopegylated-exei during surgery:

Minor surgery (e.g., tooth extraction): 50 units/kg administered preoperatively. Additional dose(s) can be administered after 24 hours if necessary.

Major surgery (e.g., intracranial, intra-abdominal, intrathoracic, or joint replacement surgery): 50 units/kg administered preoperatively. Additional doses can be administered approximately every 24 hours for the first week and then approximately every 48 hours until wound healing has occurred.

Routine Prophylaxis

The recommended starting dose is 50 units/kg every 4 days. This regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes.

Cautions for Antihemophilic Factor (recombinant), Glycopegylated-exei

Contraindications

Do not use in patients who have known hypersensitivity to antihemophilic factor (recombinant), glycopegylated-exei or its components, including hamster proteins.

Warnings/Precautions

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with antihemophilic factor (recombinant), glycopegylated-exei. The product contains traces of hamster proteins, which in some patients may cause allergic reactions. Early signs of allergic reactions, which can progress to anaphylaxis, may include angioedema, chest tightness, difficulty breathing, wheezing, rash, hives, and itching. Observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure to the product. Discontinue use of antihemophilic factor (recombinant), glycopegylated-exei if allergic- or anaphylactic-type reactions occur, and initiate appropriate treatment.

Neutralizing Antibodies

The formation of neutralizing antibodies (inhibitors) to Factor VIII has occurred following administration of antihemophilic factor (recombinant), glycopegylated-exei. Monitor patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. If expected Factor VIII activity plasma levels are not attained, or if bleeding is not controlled after antihemophilic factor (recombinant), glycopegylated-exei administration, suspect the presence of an inhibitor (neutralizing antibody).

Monitoring Laboratory Tests

If monitoring of Factor VIII is performed, use a chromogenic or one-stage clotting assay appropriate for use with antihemophilic factor (recombinant), glycopegylated-exei).

Factor VIII activity levels can be affected by the type of activated partial thromboplastin time (aPTT) reagent used in the assay. Some silica-based aPTT reagents can underestimate the activity of antihemophilic factor (recombinant), glycopegylated-exei by up to 60%; other reagents may overestimate the activity by 20%. If an appropriate one-stage clotting or chromogenic assay is not available locally, then use a reference laboratory.

If bleeding is not controlled with the recommended dose of antihemophilic factor (recombinant), glycopegylated-exei or if the expected Factor VIII activity levels in plasma are not attained, then perform a Bethesda assay to determine if Factor VIII inhibitors are present.

Specific Populations

Pregnancy

There are no data with antihemophilic factor (recombinant), glycopegylated-exei use in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with antihemophilic factor (recombinant), glycopegylated-exei. It is unknown whether antihemophilic factor (recombinant), glycopegylated-exei can cause fetal harm when administered to a pregnant woman or can affect fertility.

In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Lactation

There is no information regarding the presence of antihemophilic factor (recombinant), glycopegylated-exei in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for antihemophilic factor (recombinant), glycopegylated-exei and any potential adverse effects on the breastfed infant from antihemophilic factor (recombinant), glycopegylated-exei or from the underlying maternal condition.

Pediatric Use

Safety and efficacy were evaluated in 93 previously treated pediatric patients <18 years of age, who received at least one dose of antihemophilic factor (recombinant), glycopegylated-exei; all received routine prophylaxis.Thirty-four (34) of these subjects (36.6%) were 1 to <6 years of age; 34 subjects (36.6%) were 6 to <12 years of age; and 25 subjects (27%) were 12 to <18 years of age. Pharmacokinetic parameters were evaluated for 27 of these subjects who were treated with antihemophilic factor (recombinant), glycopegylated-exei.

No difference in the safety profile of antihemophilic factor (recombinant), glycopegylated-exei was observed between previously treated pediatric subjects and adult subjects. Pharmacokinetic studies in children <12 years of age demonstrated higher clearance, a shorter half-life, and lower incremental recovery of Factor VIII compared to adults, but the pharmacokinetic parameters are comparable between young children (1–<6 years) and older children (6–<12 years). Because clearance (per kg body weight) is higher in children (<12 years), a higher dose and more frequent dosing may be needed in this population.

Geriatric Use

Clinical studies of antihemophilic factor (recombinant), glycopegylated-exei did not include sufficient numbers of subjects age 65 years and over to determine whether or not they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease and other drug therapy.

Common Adverse Effects

The most frequently reported adverse reactions (≥ 1%) were rash, redness, itching and injection site reactions.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Antihemophilic factor (recombinant), glycopegylated-exei, a glycopegylated form of recombinant anti-hemophilic factor, temporarily replaces the missing coagulation Factor VIII needed for effective hemostasis in congenital hemophilia A patients. The Factor VIII in antihemophilic factor (recombinant), glycopegylated-exei is conjugated to a 40-kDa polyethylene glycol molecule which increases the half-life and decreases the clearance compared to the non-pegylated molecule.

Advice to Patients

Patient Counseling Information

Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Advise patients that allergic-type hypersensitivity reactions or anaphylaxis are possible with use of antihemophilic factor (recombinant), glycopegylated-exei. Inform patients of the early signs of hypersensitivity reactions including rash, hives, itching, facial swelling, tightness of the chest, and wheezing. Advise patients to discontinue use of antihemophilic factor (recombinant), glycopegylated-exei immediately and contact their healthcare provider and/or seek emergency care promptly if these symptoms occur.

Advise patients to contact their healthcare provider or treatment facility for further treatment and/or assessment if they experience a lack of a clinical response to Factor VIII replacement therapy, as this may be a manifestation of an inhibitor.

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Antihemophilic Factor (recombinant), Glycopegylated-exei

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

number of units indicated on label (nominally 500, 1000, 1500, 2000, or 3000 units)

Esperoct (with 0.9% sodium chloride for injection prefilled diluent syringe; available with vial adapter)

Novo Nordisk

AHFS Drug Information. © Copyright 2021, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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