"The U.S. Food and Drug Administration today approved Alprolix, Coagulation Factor IX (Recombinant), Fc Fusion Protein, for use in adults and children who have Hemophilia B. Alprolix is the first Hemophilia B treatment designed to require less fre"...
The clinical response to Kogenate FS may vary. If bleeding is not controlled with the recommended dose, the plasma level of factor VIII should be determined and a sufficient dose of Kogenate FS should be administered to achieve a satisfactory clinical response. If the patient's plasma factor VIII level fails to increase as expected or if bleeding is not controlled after the expected dose, the presence of an inhibitor (neutralizing antibodies) should be suspected and appropriate testing performed. [See Monitoring Laboratory Tests below.]
Anaphylaxis And Severe Hypersensitivity Reactions
Allergic-type hypersensitivity reactions including anaphylaxis have been reported with Kogenate FS and have manifested as pruritus, rash, urticaria, hives, facial swelling, dizziness, hypotension, nausea, chest discomfort, cough, dyspnea, wheezing, flushing, discomfort (generalized) and fatigue. Discontinue Kogenate FS if symptoms occur and seek immediate emergency treatment.
Kogenate FS contains trace amounts of mouse immunoglobulin G (MuIgG) and hamster (BHK) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
Patients treated with antihemophilic factor (AHF) products should be carefully monitored for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests.6 Inhibitors have been reported following administration of Kogenate FS predominantly in previously untreated patients. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, an assay that measures factor VIII inhibitor concentration should be performed. [See Monitoring Laboratory Tests below]
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. [See DOSAGE 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 Kogenate FS. Use Bethesda
Units (BU) to titer inhibitors.
- If the inhibitor is less than 10 BU per mL, the administration of additional Kogenate FS 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 Kogenate FS 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.
Patient Counseling Information
See Patient Product Information and Instructions for Use
Advise patients to report any adverse reactions or problems following Kogenate FS administration to their physician or healthcare provider.
- Allergic-type hypersensitivity reactions have been reported with Kogenate FS. Warn patients of the early signs of hypersensitivity reactions [including hives (rash with itching), generalized urticaria, tightness of the chest, wheezing, hypotension] and anaphylaxis. Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment with resuscitative measures such as the administration of epinephrine and oxygen.
- In clinical studies with Kogenate FS, a 15% incidence of inhibitor development was observed in PUPs/MTPs and zero de novo inhibitors were observed with the PTPs. Inhibitor formation may occur at any time in the treatment of a patient with hemophilia A. Advise patients to contact their physician or treatment center for further treatment and/or assessment, if they experience a lack of clinical response to factor VIII replacement therapy, as this may be a manifestation of an inhibitor.
- Advise patients to consult with their healthcare provider prior to travel. While traveling advise patients to bring an adequate supply of Kogenate FS based on their current regimen of treatment.
Preclinical studies evaluating Kogenate FS in hemophilia A with mice, rats, rabbits, and dogs demonstrated safe and effective restoration of hemostasis. Doses several fold higher than the recommended clinical dose (related to body weight) did not demonstrate any acute or subacute toxic effect for Kogenate FS in laboratory animals.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been conducted with Kogenate FS to assess its mutagenic or carcinogenic potential and impairment of fertility. Kogenate FS has been shown to be comparable to the predecessor product with respect to its biochemical and physiochemical properties, as well as its non-clinical in vivo pharmacology and toxicology. By inference, the predecessor product and Kogenate FS would be expected to have equivalent mutagenic and carcinogenic potential.
The predecessor product did not demonstrate reverse mutation or chromosomal aberrations at doses substantially greater than the maximum expected clinical dose. In vivo evaluation with the predecessor product in animals using doses ranging between 10 and 40 times the expected clinical maximum also indicated that the predecessor product did not possess a mutagenic potential. Long-term investigations of carcinogenic potential in animals have not been performed due to the immune response to heterologous proteins in all non-human mammalian species.
Use In Specific Populations
Pregnancy Category C
Animal reproduction studies have not been conducted with Kogenate FS. It is also not known whether Kogenate FS can cause fetal harm when administered to a pregnant woman or affect reproduction capacity. Kogenate FS should be used during pregnancy only if clinically needed.
Labor And Delivery
There is no information available on the effect of factor VIII replacement therapy on labor and delivery. Kogenate FS should be used only if clinically needed.
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 Kogenate FS is administered to nursing mothers. Kogenate FS should be given to nursing mothers only if clinically needed.
Safety and efficacy studies have been performed in previously untreated and minimally treated pediatric patients. Children in comparison to adults present higher factor VIII clearance values and thus lower recovery of factor VIII. This may be explained by differences in body composition7 and should be taken into account when dosing or following factor VIII levels in such a population. [See CLINICAL PHARMACOLOGY] Routine prophylactic treatment in children ages 0-2.5 years with no pre-existing joint damage has been shown to reduce spontaneous joint bleeding and the risk of joint damage. This data can be extrapolated to ages > 2.5-16 years for children who have no existing joint damage. [See Clinical Studies]
Clinical studies with Kogenate FS did not include patients aged 65 and over. Dose selection for an elderly patient should be individualized.
6. Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors. Ann NY Acad Sci 614:97-105, 1991.
7. Barnes C, Lillicrap D, Pazmino-Canizares J, et al: Pharmacokinetics of recombinant factor VIII (Kogenate-FS®) in children and causes of inter-patient pharmacokinetic variability. Haemophilia 12 (Suppl. 4): 40-49, 2006.
Last reviewed on RxList: 4/4/2014
This monograph has been modified to include the generic and brand name in many instances.
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