Introduction

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is a recombinant DNA-derived factor VIII (FVIII) concentrate composed of a single chain B-domain deleted (BDD) analogue of human FVIII covalently fused to the Fc domain of human immunoglobulin G1 (IgG1), the FVIII-binding D'D3 domain of human von Willebrand factor (VWF), and 2 XTEN polypeptides.

Uses for Antihemophilic Factor (recombinant), Fc-VWF-XTEN Fusion Protein

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl has the following uses:

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is used in adults and children with hemophilia A (congenital factor VIII deficiency) for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding.

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is not indicated for the treatment of von Willebrand disease.

Antihemophilic Factor (recombinant), Fc-VWF-XTEN Fusion Protein Dosage and Administration

General

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is available in the following dosage form(s) and strength(s):

Single-dose vials containing lyophilized powder (nominally 250, 500, 750, 1000, 2000, 3000, or 4000 IU) for reconstitution prior to IV administration.

Dosage

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

Pediatric Patients

Dosage and Administration

• Administer by IV injection (see full prescribing information for rate of administration recommendations and instructions for preparation of the drug).

• Each antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl vial label states Factor VIII activity in international units (IU or unit).

• The recommended dosage for routine prophylaxis in children is 50 IU/kg once weekly.

• The recommended dose for on-demand treatment and control of bleeding episodes and perioperative management is a single dose of 50 IU/kg; additional dose may be administered as clinically indicated (see full prescribing information for additional dosing information).

Adults

Dosage and Administration

• Administer by IV injection (see full prescribing information for rate of administration recommendations and instructions for preparation of the drug).

• Each antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl vial label states Factor VIII activity in international units (IU or unit).

• The recommended dosage for routine prophylaxis in adults is 50 IU/kg once weekly.

• The recommended dose for on-demand treatment and control of bleeding episodes and perioperative management is a single dose of 50 IU/kg; additional dose may be administered as clinically indicated (see full prescribing information for additional dosing information).

Estimated Increment of Factor VIII (IU/dL or % of normal) = 50 IU/kg × 2 (IU/dL per IU/kg).

To achieve a specific target Factor VIII activity level, use the following formula: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).

Contraindications

• Patients who have had severe hypersensitivity reactions, including anaphylaxis, to antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl or excipients in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, may occur with antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl. Allergic-type hypersensitivity reactions were not reported in the clinical trials. Inform patients of signs of hypersensitivity reactions that may progress to anaphylaxis (including hives, shortness of breath, chest tightness, wheezing, hypotension, and itching). Advise patients to discontinue use of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl if hypersensitivity symptoms occur and contact a physician and/or seek immediate emergency care.

Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to Factor VIII are possible following administration of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl. Neutralizing antibodies were not reported in the clinical trials. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. If the patient's plasma Factor VIII level fails to increase as expected or if bleeding is not controlled after administration of the drug, the presence of an inhibitor (neutralizing antibodies) should be suspected, and appropriate testing performed.

Monitoring Laboratory Tests

If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient's antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl Factor VIII activity level. Use of a reference laboratory is recommended when a qualified one-stage clotting assay or chromogenic assay is not available locally.

Monitor for the development of Factor VIII inhibitors. If bleeding is not controlled with antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl and the expected factor VIII activity plasma levels are not attained, perform an assay to determine if Factor VIII inhibitors are present (use Bethesda Units to titer inhibitors).

Specific Populations

Pregnancy

There are no data with antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl use in pregnant women to inform a drug-associated risk. Animal developmental and reproductive studies have not been conducted with the drug. Therefore, it is not known whether antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl can affect reproductive capacity or cause fetal harm when given to pregnant women.

In the U.S. general population, the estimated background risk of major birth defects 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), Fc-VWF-XTEN fusion protein-ehtl in human milk, its effects on the breastfed infant, or its 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), Fc-VWF-XTEN fusion protein-ehtl and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Pediatric Use

Safety, efficacy, and pharmacokinetics have been evaluated in 92 previously treated, pediatric patients <18 years of age who received at least one dose of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl as part of routine prophylaxis, treatment of bleeding episodes, or perioperative management. Adolescent subjects were enrolled in the adult and adolescent study and pediatric subjects <12 years of age were enrolled in an ongoing pediatric trial. Thirty-one subjects (33.7%) were <6 years of age, 36 (39.1%) subjects were 6 to <12 years of age, and 25 subjects (27.2%) were adolescents (12 to <18 years of age). Interim data from a pediatric study of the 67 subjects <12 years of age showed that no dosing adjustment was required.

Geriatric Use

Clinical studies of antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl did not include sufficient numbers of subjects 65 years of age and older to determine whether or not they respond differently from younger subjects. However, clinical experience with other Factor VIII products has not identified differences between the elderly and younger patients.

Common Adverse Effects

Most common adverse reaction (incidence >10%) are headache and arthralgia.

General

Antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl is available in the following dosage form(s) and strength(s):

Single-dose vials containing lyophilized powder (nominally 250, 500, 750, 1000, 2000, 3000, or 4000 IU) for reconstitution prior to IV administration.

Dosage

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

Pediatric Patients

Dosage and Administration

• Administer by IV injection (see full prescribing information for rate of administration recommendations and instructions for preparation of the drug).

• Each antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl vial label states Factor VIII activity in international units (IU or unit).

• The recommended dosage for routine prophylaxis in children is 50 IU/kg once weekly.

• The recommended dose for on-demand treatment and control of bleeding episodes and perioperative management is a single dose of 50 IU/kg; additional dose may be administered as clinically indicated (see full prescribing information for additional dosing information).

Adults

Dosage and Administration

• Administer by IV injection (see full prescribing information for rate of administration recommendations and instructions for preparation of the drug).

• Each antihemophilic factor (recombinant), Fc-VWF-XTEN fusion protein-ehtl vial label states Factor VIII activity in international units (IU or unit).

• The recommended dosage for routine prophylaxis in adults is 50 IU/kg once weekly.

• The recommended dose for on-demand treatment and control of bleeding episodes and perioperative management is a single dose of 50 IU/kg; additional dose may be administered as clinically indicated (see full prescribing information for additional dosing information).

Estimated Increment of Factor VIII (IU/dL or % of normal) = 50 IU/kg × 2 (IU/dL per IU/kg).

To achieve a specific target Factor VIII activity level, use the following formula: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL).

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.