Antihemophilic Factor (recombinant), Glycopegylated-exei (Monograph)

Brand name: Esperoct
Drug 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

Medically reviewed by Drugs.com on Apr 21, 2023. Written by ASHP.

Introduction

Biosynthetic (recombinant DNA origin) preparation of blood coagulation factor VIII conjugated with a polyethylene glycol (PEG) molecule.

Uses for Antihemophilic Factor (recombinant), Glycopegylated-exei

Hemophilia A

On-demand treatment and control of bleeding episodes in adults and pediatric patients with hemophilia A (congenital factor VIII deficiency, classic hemophilia).

Perioperative management of bleeding in adults and pediatric patients with hemophilia A.

Routine prophylaxis (i.e., administration at regular intervals) in adults and pediatric patients with hemophilia A to reduce frequency of bleeding episodes.

Not indicated for treatment of von Willebrand disease.

Efficacy and safety of antihemophilic factor (recombinant), glycopegylated-exei were evaluated in several multinational, open-label studies in male patients with severe hemophilia A (endogenous factor VIII activity <1%). Guidelines generally support the use of factor VIII products for prophylaxis and treatment of bleeding in patients with hemophilia A; while recombinant antihemophilic factor preparations are preferred because of their potentially superior safety profile with respect to pathogen transmission, no specific recommendation is provided regarding selection of one recombinant factor VIII concentrate over another.

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

General

Patient Monitoring

• Monitor factor VIII activity to individualize dosage and assess response to therapy. Use a chromogenic or one-stage clotting assay to monitor factor VIII activity. Adequate levels of factor VIII should be attained and maintained during therapy. Careful control of the dosage is especially important in cases of life-threatening bleeding episodes or major surgery.

• Monitor for the development of factor VIII inhibitors. Perform a Bethesda inhibitor assay if expected plasma factor VIII levels are not attained or bleeding is not controlled with recommended dosages.

• If a central venous access device (CVAD) is required, monitor for CVAD-related complications, including local infections, bacteremia, and catheter-site thrombosis.

• Monitor patients for signs and symptoms of hypersensitivity (e.g., angioedema, chest tightness, dyspnea, wheezing, rash, urticaria, pruritus).

Administration

IV Administration

Administer by slow IV injection.

Do not administer in same tubing or container with other drugs.

Reconstitution

Reconstitute lyophilized powder for injection using prefilled diluent syringe supplied by manufacturer (containing 4 mL of 0.9% saline). Reconstitution of more than 1 vial of drug may be necessary to obtain the required dose.

Administer reconstituted product immediately. If not used immediately, store reconstituted solution in the vial (with the vial adapter and the syringe attached) and use within 4 hours when stored at room temperature (≤30°C) or within 24 hours when stored at 2–8°C.

Consult manufacturer's labeling for additional instructions on reconstitution and preparation.

Rate of Administration

Infuse slowly over approximately 2 minutes.

Dosage

Dosage expressed in terms of international units (IU, units) of antihemophilic factor activity; 1 IU is equivalent to amount of factor VIII activity in 1 mL of normal human plasma. Administration of 1 IU of factor VIII per kg of body weight generally increases factor VIII activity by 2 IU/dL.

Dosage and duration of antihemophilic factor (recombinant), glycopegylated-exei therapy should be individualized based on the severity of factor VIII deficiency, location and extent of bleeding, and the patient's clinical condition. The dosage required to establish hemostasis will vary with each patient since there is considerable variability among patients in their pharmacokinetic and clinical response.

The following formula may be used as a guide to estimate the dose of antihemophilic factor (recombinant), glycopegylated-exei required to achieve a given percentage increase in plasma factor VIII:

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

The desired factor VIII level is determined by the clinical situation and severity of bleeding. For recommendations on target factor VIII levels for a given clinical situation, see the specific dosage sections for various types of uses below.

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

Hemophilia A

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:

IV

Children <12 years of age:

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

Moderate bleeding (e.g., more extensive hemarthrosis, muscle bleeding, or hematoma): 65 IU/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 IU/kg. Additional dose(s) may be administered approximately every 24 hours.

Children ≥12 years of age:

See Adult Dosage.

Perioperative Hemostasis

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:

IV

Children <12 years of age:

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

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

Children ≥12 years of age:

See Adult Dosage.

Routine Prophylaxis of Bleeding Episodes

IV

Children <12 years of age:

65 IU/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

Hemophilia A

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:

IV

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

Moderate bleeding (e.g., more extensive hemarthrosis, muscle bleeding, or hematoma): 40 IU/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 IU/kg. Additional dose(s) may be administered approximately every 24 hours.

Perioperative Hemostasis

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., dental extraction): 50 IU/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 IU/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 of Bleeding Episodes

The recommended initial dosage is 50 IU/kg every 4 days. Less or more frequent dosing may be used based on bleeding episodes.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time, although dose selection should generally be cautious, usually starting at the low end of the dosing range.

Obese and Overweight Patients

Compared to adult patients with body mass index (BMI) <25 kg/m², differences in pharmacokinetic parameters (incremental recovery of factor VIII, area under the factor VIII activity time profile, and clearance) were observed in patients who were overweight (BMI 25–<30 kg/m²) and obese (BMI 30–<35 kg/m²). Insufficient data to recommend specific dosage adjustments for overweight and obese patients at this time; however, dosage may be adjusted as needed at the clinician’s discretion.

Cautions for Antihemophilic Factor (recombinant), Glycopegylated-exei

Contraindications

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. Traces of hamster proteins contained in product may cause allergic reactions in some patients. Angioedema, chest tightness, dyspnea, wheezing, rash, urticaria, and pruritus are early signs of hypersensitivity that can progress to anaphylaxis. Observe patients for signs and symptoms of acute hypersensitivity reactions, particularly during the early phases of exposure. Discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies to Factor VIII

Neutralizing antibodies (inhibitors) to factor VIII may form. Monitor patients for development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Presence of inhibitors should be suspected if expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled following antihemophilic factor administration.

Monitoring Laboratory Tests

If monitoring for factor VIII, utilize a chromogenic or one-stage clotting assay appropriate for use with antihemophilic factor (recombinant), glycopegylated-exei. Type of activated partial thromboplastin time (aPTT) reagent used in assay can affect factor VIII activity levels. Some reagents can overestimate the activity of antihemophilic factor (recombinant), glycopegylated-exei by 20%, while certain silica-based aPTT reagents can underestimate the activity by up to 60%. Use a reference laboratory if an appropriate one-stage clotting or chromogenic assay is locally unavailable.

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

Specific Populations

Pregnancy

Unknown whether antihemophilic factor (recombinant), glycopegylated-exei can cause fetal harm or affect fertility. No data with use in pregnant women to determine if there is a drug-associated risk.

Lactation

Not known whether distributed into human milk. Effects on breast-fed infants and milk production also unknown. Consider known benefits of breast-feeding along with mother's clinical need for antihemophilic factor (recombinant), glycopegylated-exei and any potential adverse effects of the drug or underlying maternal condition on infant.

Pediatric Use

No differences in safety noted between previously treated pediatric patients. Compared to adults, pediatric patients <12 years of age had higher clearance, a shorter half-life, and lower incremental recovery of factor VIII, although the pharmacokinetic parameters were similar between young children (1–<6 years) and older children (6–<12 years). Pediatric patients <12 years of age may need a higher dose and more frequent dosing than adults because they have higher clearance.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. In general, use caution with dosage selection in geriatric patients, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function, and of concomitant disease and other drug therapy.

Hepatic Impairment

No information on use in hepatic impairment.

Renal Impairment

No information on use in renal impairment.

Common Adverse Effects

The most commonly reported adverse effects (incidence ≥1%) were rash, redness, pruritus, and injection site reactions.

Antihemophilic Factor (recombinant), Glycopegylated-exei Pharmacokinetics

Absorption

Plasma Concentrations

Incremental recovery of factor VIII in adults, pediatric patients of ages 12–<18 years, 6–<12 years, and 1–<6 years was 2.53, 2.45, 1.67, and 1.82 IU/dL per IU/kg, respectively.

Onset

The time to 5% factor VIII activity (mild hemophilia range) was 2.5 days in patients <12 years of age receiving 60 IU/kg twice weekly and 3.6, 3.6, and 4 days in those ≥12 years of age receiving 50 IU/kg twice weekly, 50 IU/kg every 4 days, and 75 IU/kg every 7 days, respectively.

Special Populations

Compared to adult patients with BMI <25 kg/m², incremental recovery was increased in patients who were overweight (BMI 25–<30 kg/m²) and obese (BMI 30–<35 kg/m²) by approximately 17% and 41%, respectively.

Distribution

Extent

Not known whether distributed into milk.

Elimination

Half-life

Following administration of a single 50-IU/kg dose in patients with severe hemophilia A, terminal half-life was 21.7 hours in adults, 17.4 hours in pediatric patients 12–<18 years of age, 13.8 hours in those 6–<12 years of age, and 14.7 hours in those 1–<6 years of age.

There was a trend of increasing AUC with age, while clearance decreased with age.

Special Populations

Compared to adult patients with BMI <25 kg/m², the following differences in pharmacokinetic parameters were observed for patients who were overweight (BMI 25–<30 kg/m²) and obese (BMI 30–<35 kg/m²): AUC was increased by approximately 10% and 27%, and clearance was decreased by approximately 8% and 23%, respectively.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package for up to 30 months from the date of manufacture until the date of expiration; do not freeze or expose to direct sunlight. During the 30-month shelf life, may be kept at room temperature up to 30°C for no longer than 12 months, or up to 40°C for no longer than 3 months.

Reconstituted Solution

If not used immediately, may store at room temperature (≤30°C) for use within 4 hours or under refrigeration (2–8°C) for use within 24 hours; protect from direct sunlight.

Actions

• Biosynthetic (recombinant DNA origin) preparation of blood coagulation factor VIII conjugated to a polyethylene glycol (PEG) molecule. Conjugation to PEG increases half-life and decreases clearance compared with the non-PEGylated molecule. PEGylation is one among several technologies that have been applied to extend the half-life of factor VIII; other recombinant factor VIII products use other technologies (such as fusion to protein conjugates or protein sequence modification).

• Patients with hemophilia A have decreased levels of endogenous factor VIII, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, joints, and internal organs. Clinical severity and frequency of bleeding generally correlate with degree of deficiency of factor VIII activity. Patients with mild hemophilia A generally have 5–<40% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.

• Administration of antihemophilic factor (recombinant), glycopegylated-exei increases plasma levels of factor VIII and temporarily corrects the coagulation defect in patients with hemophilia A. Also decreases aPTT, which is typically prolonged in such patients.

• Produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells; contains a truncated B domain, which is O-glycosylated. The recombinant factor VIII protein is purified using chromatographic steps; purification includes two viral clearance steps (detergent treatment for inactivation of enveloped viruses, and 20-nm filtration for removal of enveloped and non-enveloped viruses).

Advice to Patients

• Advise patients to read the manufacturer-provided patient information and instructions for use.

• Risk of hypersensitivity reactions. Advise patients of the early signs of hypersensitivity (e.g., rash, urticaria, itching, facial swelling, tightness of chest, wheezing) that can progress to anaphylaxis. If such symptoms occur, advise patients to immediately discontinue the drug and contact their clinician and/or seek immediate emergency care.

• Possible development of neutralizing antibodies (inhibitors). Advise patients to contact their clinician or treatment facility for further treatment and/or assessment if they experience a lack of a clinical response to antihemophilic factor (recombinant), glycopegylated-exei, since this may indicate the presence of an inhibitor.

• Advise patients to report to their clinician any adverse reactions or other issues following administration of antihemophilic factor (recombinant), glycopegylated-exei. Inform patients that common adverse effects include rash, itching, redness, and pain or swelling at the location of injection.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise patients that the risks to the mother and fetus are unknown if the drug is used during pregnancy.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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 is available only through a hemophilia treatment center, specialty pharmacy, or hemophilia home care agency. Contact the manufacturer for specific availability.

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