Antihemophilic factor recombinant

Name: Antihemophilic factor recombinant

Uses of Antihemophilic Factor (Recombinant)

Antihemophilic Factor (Recombinant) is a prescription medication used to prevent, treat, and control bleeding in adults and children with hemophilia A. This medication may also be used to prevent bleeding during surgery.

This medication is not used to treat von Willebrand Disease.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Antihemophilic Factor (Recombinant) Dosage

The dose and duration of treatment your doctor recommends will be based on the following:

  • your weight
  • your age
  • the severity of factor VIII deficiency
  • the location of the bleeding
  • your overall clinical condition
  • how you respond to this medication

What should I avoid while using recombinant antihemophilic factor?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Recombinant antihemophilic factor side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; feeling light-headed, fainting; swelling of your face, lips, tongue, or throat.

Stop using recombinant antihemophilic factor and call your doctor at once if you have:

  • chest pain;

  • easy bruising, increased bleeding episodes; or

  • bleeding from a wound or where the medicine was injected.

Common side effects may include:

  • nausea, vomiting, diarrhea;

  • headache, dizziness;

  • joint pain;

  • rash;

  • sore throat, cough, stuffy nose;

  • weakness, feeling tired;

  • fever; or

  • pain, swelling, itching, or irritation where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Introduction

Biosynthetic (recombinant DNA origin) preparation of antihemophilic factor (blood coagulation factor VIII).1 2 7 8 10 11 40 120 121 122 151 153 Structurally similar to endogenous human factor VIII and produces the same biologic effects as plasma-derived antihemophilic factor (human).1 2 3 4 7 8 9 10 40 49 50 69 77 120 121 122 151 153

Stability

Storage

Parenteral

Powder for IV Infusion

Advate: 2–8°C (avoid freezing).122 May store at room temperature of ≤30°C for up to 6 months; do not return drug to refrigerator after storage at room temperature.122

Helixate FS/Kogenate FS: 2–8°C (avoid freezing); may store at room temperature of ≤25°C for up to 12 months.120 121 Do not return to refrigerator after storage at room temperature.120 121 Protect from extreme exposure to light and store lyophilized powder in the carton prior to use.120 121

Novoeight: 2–8°C (avoid freezing) for up to 30 months; may store at room temperature of ≤30°C for up to 12 months within this period.153 Do not return to refrigerator after storage at room temperature.153 Store in original container to protect from light.153

Recombinate: 2–8°C (avoid freezing); may store at room temperature of ≤30°C.1

ReFacto: 2–8°C (avoid freezing); may store at room temperature of ≤25°C for up to 3 months.2 Do not use beyond expiration date.2 Protect from extreme exposure to light.2

Xyntha: 2–8°C; may store at room temperature of ≤25°C for up to 3 months.151 Do not return to refrigerator after storage at room temperature.151 May store prefilled diluent syringe at 2–25°C (avoid freezing to prevent damage).151 Protect from prolonged exposure to light.151

Store reconstituted solutions at room temperature; use within 3 hours (Advate, Helixate FS, Kogenate FS, Recombinate, ReFacto, Xyntha) or 4 hours (Novoeight) of reconstitution.1 2 120 121 122 151 153

Actions

  • Structurally similar to and appears to produce the same pharmacologic effects as endogenous human blood coagulation factor VIII.1 3 4 7 8 9 10 12 40 49 50 69 77

  • Factor VIII is essential for blood clotting and maintenance of hemostasis.12 23 24 73 74 82 95 96 151

  • Patients with hemophilia A have decreased levels of endogenous factor VIII or dysfunctional factor VIII, resulting in a bleeding tendency and clinical manifestations such as bleeding into soft tissues, muscles, and joints.1 4 12 23 24 41 69 73 95 96 151 Therefore, replacement therapy with exogenous antihemophilic factor is necessary.151

  • Clinical severity and frequency of bleeding generally correlate with degree of deficiency of factor VIII activity.23 24 41 73 74 Patients with mild hemophilia A generally have >5% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.23 24 95

  • Administration of antihemophilic factor (recombinant) increases plasma levels of factor VIII and temporarily corrects the coagulation defect in patients with hemophilia A.1 2 5 9 40 47 55 68 69 73 120 121 122 151 153

  • Although similar in structure and pharmacologic effects to plasma-derived human factor VIII,1 2 3 4 7 8 9 10 40 49 50 69 77 120 121 122 antihemophilic factor (recombinant) is associated with substantially reduced risk of transmission of blood-borne human viruses (e.g., HIV, HAV, HBV, HCV).3 4 8 9 14 40 49 50 68 69 73 76 110 122 246

  • Prepared by recombinant DNA technology in a mammalian cell expression system using different methods to express, isolate, harvest, and purify factor VIII.1 2 7 8 10 11 40 120 121 122 151 153

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)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

number of units indicated on label

Advate (with sterile water for injection diluent; available with administration set)

Baxter

Helixate FS (with sterile water for injection diluent; available with filter transfer device)

Bayer

Kogenate FS (with sterile water for injection diluent; available with transfer and filter needles or alternative needleless transfer systems, and administration set)

Bayer

Novoeight (with prefilled syringe containing 0.9% sodium chloride diluent; available with vial adapter)

Novo Nordisk

Recombinate (with sterile water for injection diluent; available with needleless transfer device)

Baxter

ReFacto (with prefilled syringe containing 0.9% sodium chloride diluent; available with vial adapter, alcohol swabs, bandage, gauze, and administration set)

Wyeth

Xyntha (with prefilled syringe containing 0.9% sodium chloride diluent; available with vial adapter, alcohol swabs, bandage, gauze, and administration set)

Wyeth

Dosing Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Description

ReFacto Antihemophilic Factor (Recombinant) is a purified protein produced by recombinant DNA technology for use in therapy of factor VIII deficiency. ReFacto is a glycoprotein with an approximate molecular mass of 170 kDa consisting of 1438 amino acids. It has an amino acid sequence that is comparable to the 90 + 80 kDa form of factor VIII, and post-translational modifications that are similar to those of the plasma-derived molecule. ReFacto has in vitro functional characteristics comparable to those of endogenous factor VIII.

ReFacto is produced by a genetically engineered Chinese hamster ovary (CHO) cell line. The CHO cell line secretes B-domain deleted recombinant factor VIII into a defined cell culture medium that contains human serum albumin and recombinant insulin, but does not contain any proteins derived from animal sources. The protein is purified by a chromatography purification process that yields a high-purity, active product. The potency expressed in international units (IU) is determined using the European Pharmacopoeial chromogenic assay against the WHO standard. The specific activity of ReFacto is 9110-13700 IU per milligram of protein. ReFacto is not purified from human blood and contains no preservatives or added human components in the final formulation.

ReFacto is formulated as a sterile, nonpyrogenic, lyophilized powder preparation for intravenous (IV) injection. It is available in single-use vials containing the labeled amount of factor VIII activity (IU). Each vial contains nominally 250, 500, 1000 or 2000 IU of ReFacto per vial. The formulated product is a clear colorless solution upon reconstitution and contains sodium chloride, sucrose, L-histidine, calcium chloride, and polysorbate 80.

Precautions

General

Activity-neutralizing antibodies (inhibitors) have been detected in patients receiving factor VIII-containing products. Low titer inhibitors are common in previously untreated patients and in previously treated patients on factor VIII products, as are high titer inhibitors in previously untreated patients. High titer inhibitors, which are generally rare in previously treated patients, have been reported in previously treated patients on ReFacto. As with all coagulation factor VIII products, patients should be monitored for the development of inhibitors that should be titrated in Bethesda Units using appropriate biological testing.

Reports of lack of effect, mainly in prophylaxis patients, have been received in the clinical trials and in the post-marketing setting. The reported lack of effect has been described as bleeding into target joints, bleeding into new joints or a subjective feeling by the patient of new onset bleeding. When switching to ReFacto it is important to individually titrate and monitor each patient's dose in order to ensure an adequate therapeutic response (see DOSAGE AND ADMINISTRATION ).

Formation of Antibodies to Mouse and Hamster Protein

As Antihemophilic Factor (Recombinant), ReFacto contains trace amounts of mouse protein (maximum of 5 ng/1000 IU) and hamster protein (maximum of 30 ng/1000 IU), the remote possibility exists that patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Carcinogenicity, Mutagenicity, Impairment of Fertility

ReFacto Antihemophilic Factor (Recombinant) has been shown to be nonmutagenic in the mouse micronucleus assay. No other mutagenicity studies and no investigations on carcinogenesis or impairment of fertility have been conducted.

Pregnancy Category C

Animal reproduction and lactation studies have not been conducted with ReFacto Antihemophilic Factor (Recombinant). It is not known whether ReFacto can affect reproductive capacity or cause fetal harm when given to pregnant women. ReFacto should be administered to pregnant and lactating women only if clearly indicated.

Pediatric Use

ReFacto Antihemophilic Factor (Recombinant) is appropriate for use in children of all ages, including newborns. Safety and efficacy studies have been performed both in previously treated children and adolescents (N=22, ages 8-15 years) and in previously untreated neonates, infants, and children (N=101, ages 0-52 months) (see CLINICAL PHARMACOLOGY and PRECAUTIONS ).

Geriatric Use

Clinical studies of ReFacto did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. As with any patient receiving ReFacto, dose selection for an elderly patient should be individualized.

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