Drug Class Description
Blood Coagulation Factor VIII.
Generic Name
Factor VIII [octocog alfa]
Drug Description
Powder and solvent for solution for injection. The powder is provided in a vial as a dry white to slightly yellow powder or cake. The solvent is water for injections provided in a pre-filled syringe.
Presentation
KOGENATE Bayer 1000 IU Powder and solvent for solution for injection - Recombinant Coagulation factor VIII, 1000 IU/vial - The product reconstituted with the accompanying 2.5 ml of water for injections contains approximately 400 IU octocog alfa/ml. The specific activity is approximately 4000 IU/mg protein. KOGENATE Bayer 2000 IU Powder and solvent for solution for injection - Recombinant Coagulation factor VIII, 2000 IU/vial - The product reconstituted with the accompanying 5.0 ml of water for injections contains approximately 400 IU octocog alfa/ml. The specific activity is approximately 4000 IU/mg protein.KOGENATE Bayer 250 IU Powder and solvent for solution for injection - Recombinant Coagulation factor VIII, 250 IU/vial - The product reconstituted with the accompanying 2.5 ml of water for injections contains approximately 100 IU octocog alfa/ml. The specific activity is approximately 4000 IU/mg protein.KOGENATE Bayer 500 IU Powder and solvent for solution for injection - Recombinant Coagulation factor VIII, 500 IU/vial - The product reconstituted with the accompanying 2.5 ml of water for injections contains approximately 200 IU octocog alfa/ml. The specific activity is approximately 4000 IU/mg protein.INN: octocog alfa.Recombinant Coagulation factor VIII is produced from genetically engineered baby hamster kidney cells containing the human factor VIII gene.Solvent: water for injections.
Indications
Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency).This preparation does not contain von Willebrand factor and is therefore not indicated in von Willebrand's disease.
Adult Dosage
Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia.Posology The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current WHO standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to the International Standard for factor VIII in plasma). One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma. The calculation of the required dosage of factor VIII is based on the empirical finding that 1 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by 1.5% to 2.5% of normal activity. The required dosage is determined using the following formulae:I. RequireD IU = body weight(kg)x desired factor VIII rise (% of normal)x 0.5II. Expected factor VIII rise (% of normal) = 2 x administered IU/body weight(kg)The dosage and duration of the substitution therapy must be individualised according to the patient's needs (weight, severity of disorder of the haemostatic function, the site and extent of the bleeding, the titre of inhibitors, and the factor VIII level desired). The amount to be administered and the frequency of administration should always be adapted according to the clinical effectiveness in the individual case. Under certain circumstances larger amounts than those calculated may be required, especially in the case of the initial dose. During the course of treatment, appropriate determination of factor VIII levels is advised in order to guide the dose to be administered and the frequency at which to repeat the infusions. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable. Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives.It has been shown in a clinical study performed with adult haemophilia A patients who undergo a major surgery that KOGENATE Bayer can be used for continuous infusion in surgeries (pre-, during and postoperative). In this study heparin was used to prevent thrombophlebitis at the infusion site as with any other long term intravenous infusions. For the calculation of the initial infusion rate, clearance can be obtained by performing a pre-surgery decay curve, or by starting from an average population value (3.0-3.5 ml/h/Kg) and then adjust accordingly. Infusion rate (in IU/Kg/h) = Clearance (in ml/h/Kg) x desired factor VIII level (in IU/ml)For continuous infusion, clinical and in vitro stability has been demonstrated using ambulatory pumps with a PVC reservoir. KOGENATE Bayer contains low level of polysorbate-80 as an excipient, which is known to increase the rate of di-(2-ethylhexyl)phthalate (DEHP) extraction from polyvinyl chloride (PVC) materials. This should be considered for a continuous infusion administration.For scheduled prophylaxis against bleeds in patients with severe haemophilia A, doses of 20 to 60 IU of KOGENATE Bayer per kg body weight should be given at intervals of 2 to 3 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary. Data have been obtained in 61 children under 6 years of age.Patients with inhibitorsPatients should be monitored for the development of factor VIII inhibitors. If the expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if a factor VIII inhibitor is present. If the inhibitor is present at levels less than 10 Bethesda Units (BU) per ml, administration of additional recombinant coagulation factor VIII may neutralise the inhibitor and permit continued clinically effective therapy with KOGENATE Bayer. However, in the presence of an inhibitor the doses required are variable and must be adjusted according to clinical response and monitoring of plasma factor VIII activity. In patients with inhibitor titres above 10 BU or with high anamnestic response, the use of (activated) prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) preparations has to be considered. These therapies should be directed by physicians with experience in the care of patients with haemophilia.AdministrationKOGENATE Bayer should be injected intravenously over several minutes. The rate of administration should be determined by the patient's comfort level (maximal rate of injection: 2 ml/min). KOGENATE Bayer can be infused by continuous infusion. The infusion rate should be calculated based on the clearance and the desired FVIII level. Example: for a 75 kg patient with a clearance of 3 ml/h/kg, the initial infusion rate would be 3 IU/h/kg to achieve a FVIII level of 100%. For calculation of ml/hour, multiply infusion rate in IU/h/kg by kg bw/concentration of solution (IU/ml). Higher infusion rates may be required in conditions with accelerated clearance during major bleedings or extensive tissue damage during surgical interventions.Subsequent infusion rates should be calculated based on the actual FVIII levels and recalculated clearance for each day post surgery based on the equation: clearance = infusion rate/actual FVIII level.
Child Dosage
See above.
Contra Indications
Known hypersensitivity to the active substance, to mouse or hamster protein or to any of the excipients.
Special Precautions
As with any intravenous protein product, allergic type hypersensitivity reactions are possible.Patients should be made aware that the potential occurrence of chest tightness, dizziness, mild hypotension and nausea during infusion can constitute an early warning for hypersensitivity and anaphylactic reactions. Symptomatic treatment and therapy for hypersensitivity should be instituted as appropriate. If allergic or anaphylactic reactions occur, the injection/infusion should be stopped immediately and the patient should contact their physician. In case of shock, the current medical standards for shock treatment should be observed.The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A. These inhibitors are invariably IgG immunoglobulins directed against the factor VIII procoagulant activity, which are quantified in Modified Bethesda Units (BU) per ml of plasma. The risk of developing inhibitors is correlated to the exposure to anti-haemophilic factor VIII and to genetic factors among others, this risk being highest within the first 20 exposure days. Rarely, inhibitors may develop after the first 100 exposure days. Cases of recurrence of inhibitors (low titre) have been observed after switching from one recombinant factor VIII product to another in previously treated patients with more than 100 exposure days who have a history of inhibitor development.Patients treated with recombinant coagulation factor VIII should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. See Adverse Reactions. In a clinical study about the use of continuous infusion in surgeries, heparin was used to prevent thrombophlebitis at the infusion site as with any other long term intravenous infusions.This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially “sodium free”.
Interactions
No interactions of KOGENATE Bayer with other medicinal products are known. Pregnancy and lactation: Animal reproduction studies have not been conducted with KOGENATE Bayer.Based on the rare occurrence of haemophilia A in women, experience regarding the use of KOGENATE Bayer during pregnancy and breast-feeding is not available. Therefore, KOGENATE Bayer should be used during pregnancy and lactation only if clearly indicated.
Adverse Reactions
Rash/pruritus, local reactions at injection site (eg, burning, transient erythema), hypersensitivity reactions (eg, dizziness, nausea, chest pain/ malaise, mildly reduced blood pressure), unusual taste in the mouth. Anaphylactic shock. After administration of KOGENATE Bayer mild to moderate adverse events were observed in rare cases as presented in the following table. Blood and lymphatic sytem disorders: Factor VIII inhibition. Gastrointestinal disorders: Dysgeusia, Nausea. General disorders and administration site conditions; Injection site reaction, Pyrexia. Immune system disorders: Allergic / Anaphylactic reaction. Investigations: Blood pressure abnormal. Nervous system disorders: Dizziness. Skin and subcutaneous tissue disorders: Pruritus, Rash. The formation of neutralising antibodies to factor VIII (inhibitors) is a known complication in the management of individuals with haemophilia A. In studies with recombinant factor VIII preparations, development of inhibitors is predominantly observed in previously untreated haemophiliacs. Patients should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. In clinical studies, KOGENATE Bayer has been used in the treatment of bleeding episodes in 37 previously untreated patients (PUPs) and 23 minimally treated pediatric patients (MTPs, defined as having equal to or less than 4 exposure days). Five out of 37 (14%) PUP and 4 out of 23 (17%) MTP patients treated with KOGENATE Bayer developed inhibitors: Overall 6 out of 60 (10%) with a titer above 10 BU and 3 out of 60 (5%) with a titer below 10 BU. The median number of exposure days at the time of inhibitor detection in these patients was 9 days (range 3 - 18 days). The median number of exposure days in the clinical studies was 114 (range: 4-478). Four of the five patients, who had not achieved 20 exposure days at the end of the study, ultimately achieved more than 20 exposure days in post-study follow-up and one of them developed a low titer inhibitor. The fifth patient was lost to follow-up.In clinical studies with 73 previously treated patients (PTP, defined as having more than 100 exposure days), followed over four years, no de-novo inhibitors were observed.In extensive post-registration studies with KOGENATE Bayer, involving more than 1000 patients the following was observed: Less than 0.2% PTP developed de-novo inhibitors. In a subset defined as having less than 20 exposure days at study entry, less than 11% developed de-novo inhibitors.During studies, no patient developed clinically relevant antibody titres against the trace amounts of mouse protein and hamster protein present in the preparation. However, the possibility of allergic reactions to constituents, e.g. trace amounts of mouse and hamster protein in the preparation exists in certain predisposed patients (See Contraindications and Special Precautions).
Manufacturer
Bayer
Drug Availability
(POM)
