Recombinate (antihemophilic factor recombinant) is a recombinant (lab-made) clotting factor VIII (FVIII) concentrate approved to prevent and control bleeds, including those occurring during surgery, in children and adults with hemophilia A.
Prevention and treatment of bleeding episodes, including those occurring during surgery, in hemophilia A
How does Recombinate work?
Hemophilia A is caused by mutations leading to a missing or faulty FVIII, a clotting protein in the blood. Without FVIII, the blood cannot clot normally. As a result, people with hemophilia A may experience heavy or prolonged bleeding episodes occurring either spontaneously or following an injury or surgical trauma.
Recombinate contains a recombinant version of FVIII, which is similar in structure and works in the same way as human FVIII. As such, it can be used as a replacement therapy to temporarily make up for the missing or faulty FVIII, thereby helping to prevent and control bleeding in hemophilia A patients.
The recombinant protein is made in Chinese hamster ovary cells. These cells were genetically modified in the lab by introducing a gene that enables them to make the recombinant protein.
Who can take Recombinate?
Recombinate was approved by the U.S. Food and Drug Administration in December 1992 for the prevention and control of bleeding episodes in people with hemophilia A, becoming the first recombinant FVIII concentrate to be approved in the country for that indication.
It also is approved to manage bleeding episodes before, during, and after minor or major surgical procedures.
The therapy also was approved in Europe in June 1993, but is no longer commercially available.
any ingredient in Recombinate, including calcium, histidine, human albumin, polyethylene glycol, polysorbate-80, and sodium
bovine, mouse, or hamster proteins.
Recombinate also is not indicated to treat von Willebrand disease, another bleeding disorder.
How is Recombinate administered?
Recombinate is given as a slow infusion directly into the bloodstream and can be self-administered after proper training by a doctor or hemophilia center.
The concentrate is available as an off-white to faint yellow powder supplied in single-use vials that come in five color-coded strengths:
light blue contains 250 international units (IU) of FVIII
pink contains 500 IU of FVIII
green contains 1,000 IU of FVIII
purple contains 1,500 IU of FVIII
orange contains 2,000 IU of FVIII.
The vials are packaged with 5 mL of sterile water for injection and a Baxject II needle-less transfer device that allows for an easy reconstitution, or dilution, process. When mixed together, powder and diluent create a clear, colorless to faint yellow solution that is ready to infuse within three hours of reconstitution.
How much of Recombinate is given depends on factors such as where the bleeding is located and how heavy it is, as well as on a patient’s body weight.
For on-demand treatment, and until bleeding is resolved, patients should be given a dose of Recombinate to maintain FVIII activity levels at:
20%-40% of normal, with dosing every 12-24 hours for one to three days, in the case of a minor bleeding episode (e.g., muscle or oral bleeds)
30%-60% of normal, with dosing every 12-24 hours for three days or more, in the case of more extensive bleeding (e.g., extensive muscle bleeding or hematoma)
60%-100% of normal, with dosing every 8-24 hours, in the case of a life-threatening bleeding episode (e.g., head injury or throat bleeding).
For a minor surgical procedure, such as tooth extraction, FVIII activity levels should be maintained at 60%-80% of normal. A single dose of Recombinate plus an oral antifibrinolytic medication given within one hour should be sufficient to maintain FVIII activity levels in that range and control bleeding in 70% of cases.
For a major surgical procedure, Recombinate should be given before surgery, and then every 8-24 hours to maintain FVIII activity levels at 80%-100% of normal until healing is complete.
The infusions can be done at a clinic or home at a rate of up to 5 mL per minute, based on a patient’s comfort level. Patients should not attempt to inject Recombinate unless they have received proper training on how to do the infusions from a doctor or a hemophilia treatment center.
Recombinate in clinical trials
The safety and efficacy of Recombinate were evaluated in two open-label clinical studies in people with hemophilia A who had and had not been previously treated with a plasma-derived FVIII product.
Trial in previously treated patients
In a 48-month study, 69 people with moderate or severe hemophilia A who had been previously treated with plasma-derived FVIII received Recombinate for preventive (prophylaxis) or on-demand treatment of bleeding episodes.
Among 3,481 bleeding episodes, response to treatment was rated as “good” or “excellent” in 3,195 (91.2%). Recombinate also was considered “excellent” at preventing excessive bleeding in a total of 24 minor and major surgical procedures in 13 patients.
Treatment did not result in the development of inhibitors (neutralizing antibodies against FVIII), which may stop Recombinate from working properly.
Previously untreated patients
The other study included 79 previously untreated people with severe hemophilia A who received Recombinate for prophylaxis or on-demand treatment of bleeding episodes.
Among a total of 810 bleeds, most (92%) were managed with one or two infusions of Recombinate. Also, in all but one out of the 10 surgical procedures, bleeding control was rated as “excellent” — in the other procedure, the patient had developed inhibitors and experienced excessive bleeding after the surgery.
In total, 23 patients developed inhibitors against FVIII during the study, indicating that Recombinate was about equally as likely as plasma-derived FVIII to trigger the development of inhibitors.
Common side effects of Recombinate
The most common side effects that have been reported with Recombinate during clinical trials are:
nose bleeds (epistaxis).
Allergic or hypersensitivity reactions, including anaphylaxis (a severe, whole-body allergic reaction), may occur in patients treated with Recombinate. Symptoms of an allergic reaction may include dizziness, itching, rash or urticaria (hives), swelling, tightness of the throat, shortness of breath, paleness, fever, nausea, paresthesia (burning or prickling sensations), low blood pressure, and loss of consciousness.
Because Recombinate contains trace amounts of bovine, mouse, and hamster proteins, patients treated with Recombinate may experience allergies to these nonhuman proteins. If symptoms develop, treatment should be stopped, and emergency medical attention should be sought.
Development of inhibitors
Patients on Recombinate may develop neutralizing antibodies, or inhibitors, against FVIII, which can prevent the therapy from working as intended. The risk of developing inhibitors is highest in the first 20 days of treatment. This is most common in patients who have not been previously treated (or have been minimally treated) with replacement therapy.
If the expected FVIII activity levels are not reached, or if bleeding is not brought under control with an appropriate dose, a blood test may be done to check for the presence of inhibitors.
Use in pregnancy and breastfeeding
It is not known if Recombinate can affect a developing fetus during pregnancy, if it passes into breast milk, or is safe for the breastfed infant.
Women who are pregnant, planning to become pregnant, or breastfeed should talk to their doctor before taking Recombinate. The medication should only be administered in these circumstances if the potential benefits to the mother clearly outweigh the potential risks to the developing fetus or infant.
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