"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
Identification of the clotting defect as a Factor VIII deficiency is essential before the administration of Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM is initiated. No benefit may be expected from this product in treating other deficiencies.
The formation of neutralizing antibodies, inhibitors, to factor VIII is a known complication in the management of individuals with hemophilia A. The reported prevalence of these anti-bodies in patients receiving plasma derived AHF is 10-20%3, 4, 5, 6, 7 10, 11, 12. These inhibitors are invariably IgG immunoglobulins, the factor VIII procoagulant inhibitory activity of which is expressed as Bethesda Units (B.U.) per mL of plasma or serum3, 4, 5, 6, 7. Over the investigational period, none of the 65 previously treated individuals, without an inhibitor at entry into the study, developed an inhibitor.
In the previously untreated patient group there were 66 patients with factor VIII levels less than or equal to 2% who were tested for inhibitor after treatment with Bioclate (antihemophilic factor) TM rAHF. Of this group 12 individuals developed detectable inhibitor and of these, 3 patients showed a titer greater than 10 B.U. The true immunogenicity of Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM is uncertain at this time. Patients treated with rAHF should be carefully monitored for the development of antibodies to rAHF by appropriate clinical observations and laboratory tests.
As Antihemophilic Factor (Recombinant), Bioclate (antihemophilic factor) TM contains trace amounts of mouse protein (maximum of 0.1 ng/IU rAHF), hamster protein (maximum of 1 ng CHO protein/IU rAHF), and bovine protein (maximum of 1 ng BSNIU rAHF), the remote possibility exists that patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
Information for Patients
Although allergic type hypersensitivity reactions were not observed in any patient receiving Bioclate (antihemophilic factor) TM on study, such reactions are theoretically possible. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physician if these symptoms occur.
Although dosage can be estimated by the calculations which follow, it is strongly recommended that whenever possible, appropriate laboratory tests be performed on the patients plasma at suitable intervals to assure that adequate AHF levels have been reached and are maintained.
If the patients plasma AHF fails to reach expected levels or if bleeding is not controlled after adequate dosage, the presence of inhibitor should be suspected. By performing appropriate laboratory procedures, the presence of an inhibitor can be demonstrated and quantified in terms of AHF International Units neutralized by each mL of plasma or by the total estimated plasma volume. If the inhibitor is present at levels less than 10 Bethesda Units per mL, administration of adthtional AHF may neutralize the inhibitor. Thereafter the administra tion of additional AHF International Units should elicit the predicted response. The control of AHF levels by laboratory assay is necessary in this situation.
Inhibitor titers above 10 Bethesda Units per mL may make hemostasis control with AHF either impossible or impractical because of the very large dose required. In addition, the inhibitor titer may rise following AHF infusion because of an anamnestic response to the AHF antigen.
Bioclate (antihemophilic factor) † was tested for mutagenicity at doses considerably exceeding plasma concentrations of rAHF 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.
Bioclate (antihemophilic factor) TM 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).
Pregnancy Category C. Animal reproduction studies have not been conducted with Antihemophilic Factor (Recombinant). It is not known whether Antihemophilic Factor (Recombinant) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Antihemophilic Factor (Recombinant) should be given to a pregnant woman only if clearly needed.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
Additional Bioclate Information
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