Antihemophilic Factor (Recombinant), Single Chain (Monograph)

Brand name: Afstyla
Drug class: Hemostatics

Introduction

Antihemophilic factor (recombinant), single chain is a recombinant preparation of factor VIII consisting of a single polypeptide chain with a truncated B-domain with covalent linkage between factor VIII heavy and light chains.¹

Uses for Antihemophilic Factor (Recombinant), Single Chain

Antihemophilic factor (recombinant), single chain has the following uses:

Antihemophilic factor (recombinant), single chain is indicated in adults and children with hemophilia A (congenital Factor VIII deficiency) for the on-demand treatment and control of bleeding episodes, routine prophylaxis to reduce the frequency of bleeding episodes, and perioperative management of bleeding. ¹

Antihemophilic factor (recombinant), single chain is not indicated for the treatment of von Willebrand disease.¹

Antihemophilic Factor (Recombinant), Single Chain Dosage and Administration

General

Antihemophilic factor (recombinant), single chain is available in the following dosage form(s) and strength(s):

Antihemophilic factor (recombinant), single chain is available as a white or slightly yellow lyophilized powder supplied in single-dose vials containing nominally 250, 500, 1000, 1500, 2000, 2500, or 3000 International Units (IU).¹

Dosage

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

Adults and Pediatric Patients

• For IV use after reconstitution only.¹

• Administer by IV injection at a rate of administration determined by the patient's comfort level; do not exceed an infusion rate of 10 mL per minute.¹ See Full Prescribing Information for additional instructions on preparation and administration.¹

• Each vial of antihemophilic factor (recombinant), single chain is labeled with the amount of recombinant Factor VIII in international units (IU or unit).¹ One unit per kilogram body weight will raise the Factor VIII level by 2 IU/dL.¹

• Plasma Factor VIII levels can be monitored using either a chromogenic assay or a one-stage clotting assay – routinely used in US clinical laboratories.¹ If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the patient's Factor VIII activity level.¹

Calculating Required Dose:¹

Dose (IU) = Body Weight (kg) × Desired Factor VIII Rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)¹

On-demand Treatment and Control of Bleeding Episodes:

See Full Prescribing Information for a dosing guide for on-demand treatment of bleeding based on the type of bleeding (minor, moderate, or major/life-threatening).¹ Consideration should be given to maintaining a Factor VIII activity at or above the target range.¹

Routine Prophylaxis:¹

• Adults and adolescents (≥12 years): The recommended starting regimen is 20 to 50 IU per kg of antihemophilic factor (recombinant), single chain administered 2 to 3 times weekly.¹

• Children (<12 years): The recommended starting regimen is 30 to 50 IU per kg of antihemophilic factor (recombinant), single chain administered 2 to 3 times weekly.¹ More frequent or higher doses may be required in children <12 years of age to account for the higher clearance in this age group.¹

• The regimen may be adjusted based on patient response.¹

Perioperative Management:¹

See Full Prescribing Information for a dosing guide for perioperative management of bleeding based on the type of surgery (minor or major).¹ Consideration should be given to maintaining a Factor VIII activity at or above the target range.¹

Cautions for Antihemophilic Factor (Recombinant), Single Chain

Contraindications

Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis to antihemophilic factor (recombinant), single chain or its excipients, or hamster proteins.¹

Warnings/Precautions

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with antihemophilic factor (recombinant), single chain.¹ Inform patients of the early signs of hypersensitivity reactions that may progress to anaphylaxis (including hives, generalized urticaria, tightness of the chest, wheezing, hypotension and pruritus).¹ Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.¹

For patients with previous hypersensitivity reactions, consider premedication with antihistamines.¹

Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to Factor VIII has been reported following administration of antihemophilic factor (recombinant), single chain; previously untreated patients (PUPs) are at greatest risk.¹ Monitor patients for the development of neutralizing antibodies (inhibitors) by appropriate clinical observations and laboratory tests.¹ If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled after antihemophilic factor (recombinant), single chain administration, the presence of an inhibitor (neutralizing antibody) should be suspected.¹

Contact a specialized hemophilia treatment center if a patient develops an inhibitor.¹

Monitoring Laboratory Tests

Monitor plasma Factor VIII activity in patients receiving antihemophilic factor (recombinant), single chain using either the chromogenic assay or the one-stage clotting assay, which is routinely used in US clinical laboratories.¹ The chromogenic assay result most accurately reflects the clinical hemostatic potential of antihemophilic factor (recombinant), single chain and is preferred.¹ The one-stage clotting assay result underestimates the Factor VIII activity level compared to the chromogenic assay result by approximately one-half.¹ If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the patient's Factor VIII activity level.¹ Incorrect interpretation of the Factor VIII activity obtained by the one-stage clotting assay could lead to unnecessary additional dosing, higher chronic dosing, or investigations for an inhibitor.¹

Monitor for the development of Factor VIII inhibitors.¹ Perform a Bethesda inhibitor assay if expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of antihemophilic factor (recombinant), single chain.¹ Use Bethesda Units (BU) to report inhibitor levels.¹

Specific Populations

Pregnancy

There are no data with antihemophilic factor (recombinant), single chain use in pregnant women to inform on drug-associated risk.¹ No developmental or animal reproduction toxicity studies were conducted with antihemophilic factor (recombinant), single chain.¹ Thus, the risk of developmental toxicity including, structural abnormalities, embryo-fetal and/or infant mortality, functional impairment, and alterations to growth is not known.¹ In the US general population, the estimated background risk of major birth defects occurs in 2-4% of the general population and miscarriage occurs in 15-20% of clinically recognized pregnancies.¹

Lactation

There is no information regarding the excretion of antihemophilic factor (recombinant), single chain in human milk, the effect on the breastfed infant, or the effects on milk production.¹ The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for antihemophilic factor (recombinant), single chain and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.¹

Pediatric Use

Safety and efficacy studies with antihemophilic factor (recombinant), single chain have been performed in 98 PTPs <18 years of age and in 24 PUPs ≤5 years.¹ Fourteen adolescent subjects ≥12 to <18 years were enrolled in the adult/adolescent safety and efficacy study.¹ Thirty-five subjects 0 to <6 years and 49 subjects ≥6 to <12 years were enrolled in a pediatric safety and efficacy study.¹ Because clearance (based on per kg body weight) has been shown to be higher in the pediatric population 0 to <12 years, more frequent or higher doses of antihemophilic factor (recombinant), single chain based on body weight may be needed. ¹

Geriatric Use

Clinical studies of antihemophilic factor (recombinant), single chain did not include subjects over 65 years of age to determine whether or not they respond differently from younger subjects.¹

Common Adverse Effects

• The most common adverse reactions reported in clinical trials (>0.5% of subjects) were Factor VIII inhibition in previously untreated patients (PUPs), dizziness, and hypersensitivity.¹

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), single chain is a recombinant protein that replaces the missing Coagulation Factor VIII needed for effective hemostasis.¹ Antihemophilic factor (recombinant), single chain is a single polypeptide chain with a truncated B-domain that allows for a covalent bridge to link the Factor VIII heavy and light chains.¹ Antihemophilic factor (recombinant), single chain has demonstrated a higher von Willebrand Factor (VWF) affinity relative to full-length rFVIII.¹ VWF stabilizes Factor VIII and protects it from degradation.¹ Activated antihemophilic factor (recombinant), single chain has an amino acid sequence identical to endogenous FVIIIa.¹

Advice to Patients

• Advise patients to read the FDA-approved Patient Labeling (Patient Product Information and Instructions for Use).¹

• Advise patients to discontinue use of antihemophilic factor (recombinant), single chain in case of a hypersensitivity reaction and contact their healthcare provider and/or seek emergency care, depending on the severity of the reaction.¹ Early signs of hypersensitivity reactions may include hives, itching, facial swelling, tightness of the chest, and wheezing.¹

• Advise patients to contact their healthcare provider or hemophilia treatment facility for further treatment and/or assessment if they experience a lack of clinical response to Factor VIII replacement therapy, as in some cases this may be a manifestation of an inhibitor.¹

• Advise patients to report any adverse reactions or problems following antihemophilic factor (recombinant), single chain administration to their healthcare provider.¹

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.

Related/similar drugs

Medical Disclaimer