Package Insert
Indications and Usage
Kogenate® FS Antihemophilic Factor (Recombinant) (rFVIII) is indicated for the treatment of classical hemophilia (hemophilia A) in which there is a demonstrated deficiency of activity of the plasma clotting factor FVIII. Kogenate® FS provides a means of temporarily replacing the missing clotting factor in order to correct or prevent bleeding episodes, or in order to perform emergency or elective surgery in hemophiliacs.
In clinical studies with the predecessor product Kogenate®, some patients who developed inhibitors on study continued to manifest a clinical response when inhibitor titers were less than 10 Bethesda Units (BU) per mL. When an inhibitor is present, the dosage requirement for FVIII is variable. The dosage can be determined only by clinical response, and by monitoring circulating FVIII levels after treatment (see Dosage and Administration). Because Kogenate® FS has similar biological activity to Kogenate® it can be used in the same manner.
Kogenate® FS does not contain von Willebrand's factor and therefore is not indicated for the treatment of von Willebrand's disease.
Important Safety Information
CONTRAINDICATIONS
Known intolerance or allergic reactions to constituents of the preparation.
Known hypersensitivity to mouse or hamster protein may be a contraindication to the use of Kogenate® FS.
WARNINGS
None.
PRECAUTIONS
General
Kogenate® FS Antihemophilic Factor (Recombinant) is intended for the treatment of bleeding disorders arising from a deficiency in FVIII. This deficiency should be proven prior to administering Kogenate FS. The development of circulating neutralizing antibodies to FVIII may occur during the treatment of patients with hemophilia A. Inhibitor formation is especially common in young children with severe hemophilia during their first years of treatment, or in patients of any age who have received little previous treatment with FVIII. Nonetheless, inhibitor formation may occur at any time in the treatment of a patient with hemophilia A. Patients treated with any AHF preparation, including Kogenate FS, should be carefully monitored for the development of antibodies to FVIII by appropriate clinical observation and laboratory tests, according to the recommendation of the patient's hemophilia treatment center.
Among patients treated with antihemophilic factor concentrates, cases of hypotension, urticaria, and chest tightness in association with hypersensitivity reactions have been reported in the literature. Very rare cases of allergic and anaphylactic reactions have been reported with the predecessor product KOGENATE® Antihemophilic Factor (Recombinant), particularly in very young patients or patients who have previously reacted to other FVIII concentrates (see ADVERSE REACTIONS-Post-marketing experience). Serious anaphylactic reactions require immediate emergency treatment with resuscitative measures such as the administration of epinephrine and oxygen.
Formation of Antibodies to Mouse and Hamster Protein
Assays to detect seroconversion to mouse and hamster protein were conducted on all patients in clinical studies. No patient has developed specific antibodies to these proteins after commencing study, and no animal protein associated serious allergic reactions have been observed with rFVIII-FS infusions. Although no such reactions were observed, patients should be made aware of the possibility of a hypersensitivity reaction to mouse and/or hamster protein, and alerted to the early signs of such a reaction (e.g., hives, localized or generalized urticaria, wheezing, and hypotension). Patients should be advised to discontinue use of the product and contact their physician if such symptoms occur.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In vitro evaluation of the mutagenic potential of rFVIII failed to demonstrate reverse mutation or chromosomal aberrations at doses substantially greater than the maximum expected clinical dose. In vivo evaluation of rFVIII in animals using doses ranging between 10 and 40 times the expected clinical maximum also indicated that rFVIII does not possess a mutagenic potential. Long-term investigations of carcinogenic potential in animals have not been performed.
Pediatric Use
Kogenate FS is appropriate for use in pediatric patients of all ages, including neonates, infants, children, and adolescents. Safety and efficacy studies have been performed in previously untreated and minimally treated pediatric patients (n=62). Kogenate FS is similar to KOGENATE® Antihemophilic Factor (Recombinant) in its biological activity and may be used in pediatric patients in the same manner as KOGENATE.
Geriatric Use
Clinical studies with Kogenate FS did not include sufficient numbers of patients aged 65 and over to be able to determine whether they respond differently from younger patients. However, clinical experience with KOGENATE and other AHF products has not identified differences between the elderly and younger patients. As with any patient receiving Kogenate FS, dose selection for an elderly patient should be individualized.
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 and lactation only if clearly indicated.
ADVERSE REACTIONS
During the clinical studies conducted in previously treated patients (PTPs), 109 adverse events were reported in the course of 4160 infusions (2.6%). Only 13 events were reported by the investigator as at least remotely related to study drug. Another 7 events were nonassessable. Thus 20 events in 11 patients were considered to be either nonassessable or at least remotely related to Kogenate® FS Antihemophilic Factor (Recombinant) administration, for an incidence of 0.5% relative to the number of infusions administered. Events that were at least remotely drug-related included: local injection site reactions (2), dizziness (2), rash (2), unusual taste in the mouth (1), mild increase in blood pressure (1), pruritus (1), depersonalization (1), nausea (1), and rhinitis (1). No FVIII inhibitors have developed in the 72 PTPs with severe hemophilia A who have received Kogenate FS for a mean of 54 exposure days.
In clinical studies with previously untreated patients (PUPs) and minimally treated (MTP) pediatric patients, 18 adverse events were reported by the clinical investigators as at least possibly related to the study drug including the expected complication of inhibitor development in 8 patients (included in the 10 patients discussed in the package insert under CLINICAL PHARMACOLOGY), a forearm bleed following venipuncture, constipation, adenopathy, rash, anemia and pallor in one inhibitor patient with gastroenteritis, and serous otitis media.
Post-marketing experience
The following events are principally derived from post-marketing experience and publications and accurate rate estimates are generally not possible. Among patients treated with its predecessor product KOGENATE® Antihemophilic Factor (Recombinant), very rare cases of serious allergic reactions and anaphylactic reactions have been reported, particularly in very young patients or patients who had previously reacted to other FVIII concentrates. Individual cases of hypotension have been very rarely reported. Rare cases of urticaria have also been reported. Although such serious reactions have not been reported with the use of Kogenate FS Antihemophilic Factor (Recombinant), Formulated with Sucrose, it is likely that these may also occur. Rare cases of dyspnea have been reported with Kogenate FS.
Full Package Insert
|
