Recombinate

RECOMBINATE, Antihemophilic Factor (Recombinant) (rAHF) is a glycoprotein synthesized by a genetically engineered Chinese Hamster Ovary (CHO) cell line. In culture, the CHO cell line secretes recombinant antihemophilic factor (rAHF) into the cell culture medium. The rAHF is purified from the culture medium utilizing a series of chromatography columns. A key step in the purification process is an immunoaffinity chromatography methodology in which a purification matrix, prepared by immobilization of a monoclonal antibody directed to factor VIII, is utilized to selectively isolate the rAHF in the medium. The synthesized rAHF produced by the CHO cells has the same biological effects as Antihemophilic Factor (Human) [AHF (Human)]. Structurally the protein has a similar combination of heterogenous heavy and light chains as found in AHF (Human).

RECOMBINATE (antihemophilic factor recombinant) rAHF is formulated as a sterile, nonpyrogenic, off- white to faint yellow, lyophilized powder preparation of concentrated recombinant AHF for intravenous injection. RECOMBINATE (antihemophilic factor recombinant) rAHF is available in single-dose bottles which contain nominally 250, 500 and 1000 International Units per bottle. When reconstituted with the appropriate volume of diluent, the product contains the following stabilizers in maximum amounts: 12.5 mg/mL Albumin (Human), 0.20 mg/mL calcium, 1.5 mg/mL polyethylene glycol (3350), 180 mEq/L sodium, 55 mM histidine, 1.5 µg/AHF international Unit (IU) polysorbate-80. Von Willebrand Factor (vWF) is coexpressed with the Antihemophilic Factor (Recombinant) and helps to stabilize it. The final product contains not more than 2 ng vWF/IU rAHF which will not have any clinically relevant effect in patients with von Willebrand's disease. The product contains no preservative.

Manufacturing of RECOMBINATE (antihemophilic factor recombinant) rAHF is shared by Baxter Healthcare Corporation and Wyeth BioPharma. The recombinant Antihemophilic Factor Concentrate (For Further Manufacturing Use), is produced by Baxter Healthcare Corporation and Wyeth BioPharma (For Further Manufacturing Use) and subsequently formulated and packaged at Baxter Healthcare Corporation.

Each bottle of RECOMBINATE (antihemophilic factor recombinant) rAHF is labeled with the AHF activity expressed in IU per bottle. Biological potency is determined by an in vitroassay which is referenced to the World Health Organization (WHO) International Standard for Factor VIII:C Concentrate.

None.

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

During the clinical studies conducted in the previously treated patient group, there were 13 infusion related minor adverse reactions reported out of 10,446 infusions (0.12%).

One patient experienced flushing and nausea during his first infusion which abated on decreasing the infusion rate. A second patient experienced mild fatigue during and following one infusion and a third patient had a series of eleven nose bleeds with a periodicity associated with the infusions.

The protein in greatest concentration in RECOMBINATE (antihemophilic factor (recombinant)) rAHF is Albumin (Human). Reactions associated with intravenous administration of albumin are extremely rare, although nausea, fever, chills or urticaria have been reported. Other allergic reactions could theoretically be encountered in the use of this Antihemophilic Factor preparation. See Information for Patients.

Read the entire FDA prescribing information for Recombinate (Antihemophilic Factor (Recombinant))

Recombinate is a prescription medication used to prevent bleeding episodes in children and adults with hemophilia A (cogenital factor VIII deficiency). 

Recombinate belongs to a group of drugs called clotting factors. It works by replacing a protein in the blood that is needed to control bleeding that people with hemophilia A are missing.

This medication comes in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of Recombinate chills, flushing, rash, and nose bleeds.

No drug interactions have been evaluated by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Recombinate comes in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Recombinate may be infused at a hemophilia treatment center or in your doctor's office. You may also be trained to do infusions at home. Do not attempt to do an infusion at home by yourself unless you have been taught how to do this by your doctor or hemophilia center. Always follow your healthcare provider's specific instructions on how to mix and administer Recombinate.

If you miss a dose or miss an appointment to receive a dose of Recombinate, contact your healthcare provider for instructions on when to receive your next dose.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

General

Certain components used in the packaging of this product contain natural rubber latex.

Identification of the clotting defect as a Factor VIII deficiency is essential before the administration of Recombinate [Antihemophilic Factor (Recombinant)] is initiated. No benefit may be expected from this product in treating other deficiencies.

Formation of Antibodies to Mouse, Hamster or Bovine Protein

As Recombinate contains trace amounts of mouse protein (maximum of 0.1 ng/IU Recombinate), hamster protein (maximum of 1.5 ng CHO protein/IU Recombinate), and bovine protein (maximum of 1 ng BSA/IU Recombinate), the remote possibility exists that patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Information for Patients

The patient and physician should discuss the risks and benefits of this product.

Allergic type hypersensitivity reactions have been observed with Recombinate. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, symptoms of laryngeal edema, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physician if these symptoms occur. Additionally, patients should be informed that local tissue irritation may occur when infusing Recombinate reconstituted with 5 mL sWFI.

Monitoring Laboratory Tests

• Monitor plasma factor VIII activity levels by the one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained, when clinically indicated. (seeDOSAGE AND ADMINISTRATION).
• Monitor for development of factor VIII inhibitors. Perform assay to determine if factor VIII inhibitor is present if expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with the expected dose of Recombinate. Use Bethesda Units (BU) to titer inhibitors.
• If the inhibitor is less than 10 BU per mL, the administration of additional Recombinate concentrate may neutralize the inhibitor, and may permit an appropriate hemostatic response.
• Adequate hemostasis may not be achieved if Inhibitor titers are above 10 BU per mL. The inhibitor titer may rise following Recombinate infusion as a result of an anamnestic response to factor VIII. The treatment or prevention of bleeding in such patients requires the use of alternative therapeutic approaches and agents.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Recombinate was tested for mutagenicity at doses considerably exceeding plasma concentrations of Factor VIII in vitro and at doses up to ten times the expected maximum clinical dose in vivo, and did not cause reverse mutations, chromosomal aberrations, or an increase in micronuclei in bone marrow polychromatic erythrocytes. Long-term studies in animals have not been performed to evaluate carcinogenic potential.

Pediatric Use

Recombinate is appropriate for use in children of all ages, including the newborn. Safety and efficacy studies have been performed in both previously treated (n=23) and previously untreated (n=75) children. (See Clinical Pharmacology and Precautions).

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Recombinate. The safety of Recombinate for use in pregnant women has not been established. It is not known whether Recombinate can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing Recombinate. Recombinate should be given to a pregnant woman only if clearly needed.

Nursing Mother

It is not known whether this drug is excreted into human milk. Because many drugs are excreted into human milk, caution should be exercised if Recombinate is administered to nursing mothers. Recombinate should be given to nursing mothers only if clinically needed.

Over the investigational period of the original safety and efficacy study of Recombinate, none of the 69 subjects without an inhibitor at entry into the study, developed an inhibitor. In the previously untreated patient group there were 73 eligible subjects with Factor VIII levels less than or equal to 2% who received at least one Recombinate treatment (median days 100, range 3-821) and who were tested for an inhibitor after treatment with Recombinate. Of this group, 23 individuals (32%) developed a detectable inhibitor (median days on treatment at time of detection 10, range 3-69) and of these, 8 subjects (11%) showed a titer greater than 10 B.U.