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RECOMBINATE

RECOMBINATE^TM [Antihemophilic Factor (Recombinant)] (rAHF) is a prescription medication that contains a synthetic glycoprotein, which replaces factor VIII, also known as antihemophilic factor (AHF). This clotting factor is absent or deficient in individuals with hemophilia A.¹ RECOMBINATE is jointly manufactured by Baxter Healthcare Corporation and Wyeth BioPharma.²

RECOMBINATE is produced by a genetically engineered Chinese hamster ovary cell line, which secretes rAHF into the cell culture medium. This rAHF is purified using immunoaffinity chromatography, which specifically isolates the rAHF from the rest of the medium. This process uses a purification matrix that immobilizes a monoclonal antibody that targets factor VIII. Following purification, rAHF is concentrated into a faint yellow to off-white, lyophilized powder that is dissolved in a specified amount of diluent prior to intravenous injection.²

When properly reconstituted, the final rAHF product contains 12.5 mg/mL albumin (human), 0.20 mg/mL calcium, 1.5 mg/mL polyethylene glycol, 180 mEq/L sodium, 55 mM histidine, 1.5 µg/AHF (IU) polysorbate-80, and no more than 2 mg of von Willebrand factor to assist in stabilizing rAHF.Each bottle of rAHF is labeled as containing 250 IU, 500 IU, or 1000 IU per bottle.²

Indications

rAHF is indicated for use in individuals with classic hemophilia A to control acute bleeding episodes and to prophylactically prevent bleeding episodes, especially preoperatively. rAHF also has a therapeutic benefit for individuals with acquired AHF inhibitors less than 10 Bethesda Units per mL.²

RECOMBINATE is not intended to treat individuals with von Willebrand disease.¹

Dosage and Administration

The proper dosages of rAHF must be determined by frequent laboratory tests, which measure circulating AHF levels that direct physician dosage prescription to reach a new target level of circulating AHF. An estimation of the peak in vivo increase of circulating AHF (expressed as IU/dL of plasma or percentage of normal circulating AHF) is calculated by multiplying the administered dose per kg body weight (IU/kg) by 2. This dosage calculation is based on the results of 419 clinical pharmacokinetic studies that supported the initial findings in a study conducted in 1966.^2,3

Different peak AHF concentration levels are recommended for varying degrees of hemorrhaging. Minor hemarthroses, muscle bleeds, or oral bleeds require 20% to 40% of normal AHF levels, whereas major hemarthroses, muscle bleeds, or oral bleeds require 30% to 60% of normal AHF levels. Life-threatening bleeds including head injury, throat bleeds, severe abdominal pain, and any minor or major surgeries require between 60% to 100% of normal AHF levels.²

The powder concentrate of rAHF is reconstituted in sterile water and administered at a rate of up to 10 mL per minute via intravenous injection using aseptic techniques. Prior to and during intravenous administration, the pulse rate should be monitored. When a significant increase in pulse rate occurs, symptoms disappear immediately upon cessation of the injection or reduction in the rate of administration.²

Get full prescribing information on RECOMBINATE at MPR

Mechanism of Action

RECOMBINATE administration increases plasma concentration of factor VIII or AHF in patients with hemophilia A who are deficient in this clotting factor. This temporarily fixes the coagulation defect in these patients during acute bleeding episodes or for bleeding prophylaxis.²

Trial Efficacy and Safety of RECOMBINATE

In 1994, researchers participated in a multicenter study analyzing the clinical efficacy and safety of RECOMBINATE in previously untreated patients with severe hemophilia A. They reported 92% efficacy in controlling 810 bleeding episodes in 71 patients requiring a total of 1785 RECOMBINATE infusions. Seventeen of the 71 (23.9%) patients receiving at least 1 infusion of RECOMBINATE developed inhibitors to factor VIII.⁴

In 1997, researchers participated in a prospective, open-label, multicenter study analyzing the clinical efficacy and safety of RECOMBINATE in 69 previously treated patients with hemophilia A (67 severe, 2 moderate). The researchers reported 91.2% good or excellent efficacy in controlling 3195 of the 3481 documented bleeding episodes. Hemostasis following preoperative prophylaxis was excellent in all 13 patients who underwent 24 surgical procedures. Only mild adverse reactions were reported in 0.096% (13 of 13,591) RECOMBINATE infusions, and no patients in this study developed factor VIII inhibitors.⁵

Warnings, Precautions, and Adverse Reactions

Individuals with latex allergies must be made aware that packaging of the product contains natural rubber latex. RECOMBINATE may be contraindicated in individuals with known hypersensitivities to nonhuman hamster, bovine, or mouse proteins. Individuals undergoing rAHF intravenous injection should be monitored for the development of hypersensitivities to these nonhuman proteins or neutralizing factor VIII antibodies.²

Clinical trials have not yet determined if fetal harm or altered reproductive capacity occurs if RECOMBINATE is used in pregnant women; therefore, it has obtained a category C classification for use during pregnancy. It is safe for use in pediatric cases.²

Reported adverse effects include nausea, fever, chills, urticaria, flushing, mild fatigue, and nosebleeds, most of which may be the result of reactions to the albumin that is administered along with rAHF.^1,2

References

RECOMBINATE^TM [antihemophilic factor (recombinant)]. RECOMBINATE. Accessed December 30, 2021.
Recombinate (antihemophilic factor (recombinant)): uses, dosage, side effects, interactions, warning. RxList. Updated December 29, 2016. Accessed December 30, 2021.
Abildgaard CF, Simone JV, Corrigan JJ, et al. Treatment of hemophilia with glycine-precipitated factor VIII. N Engl J Med. 1966;275(9):471-475. doi:10.1056/NEJM196609012750904
Bray GL, Gomperts ED, Courier S, et al. A multicenter study of recombinant factor viii (Recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. Blood. 1994;83(9):2428-2435. doi:10.1182/blood. V83.9.2428.2428
White GC, Courter S, Bray GL, Lee M, Gomperts ED. A multicenter study of recombinant factor VIII (Recombinate^TM) in previously treated patients with hemophilia A. Thromb Haemost. 1997;77(4):660-667. doi:10.1055/s-0038-1656030

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.

Hemophilia