AFSTYLA POWDER AND SOLVENT FOR SOLUTION FOR INJECTION 3000IU/VIAL

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**4.2 Posology and method of administration** Initiate treatment of AFSTYLA under the supervision of a physician experienced in the treatment of hemophilia. The decision for an individual patient on the use of home treatment of bleeding and prophylaxis of bleeding in patients with hemophilia A should be made by the treating physician who should ensure that appropriate training is provided and the use is reviewed at intervals. Posology The dose and duration of the treatment depend on the severity of the factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. 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 an International Standard for factor VIII in plasma). Each vial label of AFSTYLA states the factor VIII potency in International Units (IU). One international unit corresponds to the activity of factor VIII contained in one milliliter of normal human plasma. Potency assignment is determined using a chromogenic substrate assay. Plasma factor VIII levels can be monitored using either a chromogenic substrate assay or a one-stage clotting assay. If using the one-stage clotting assay to monitor FVIII activity level, the one-stage assay results can be aligned to chromogenic substrate acquired results by multiplying the one-stage result by 2 (see 4.4 Special Warnings and Precautions for Use – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). On demand treatment Calculation of the required dose of factor VIII is based on the empirical finding that 1 international unit factor VIII per kg body weight raises the plasma factor VIII activity by 2 international units/dL. The expected _in vivo_ peak increase in factor VIII level expressed as international units/dL (or % of normal) is estimated using the following formula: Estimated Increment of factor VIII (IU/dL or % of normal) = \[Total Dose (IU)/body weight (kg)\] x 2 (IU/dL per IU/kg) The dose to achieve a desired _in vivo_ peak increase in factor VIII level may be calculated using the following formula: Dose (IU) = body weight (kg) x Desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL) The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case. A guide for dosing AFSTYLA for the control and prevention of bleeding episodes is provided in the following table. Consideration should be given to maintaining a factor VIII activity at or above the target range:  Prophylaxis The recommended starting regimen is 20 to 50 international units/kg of AFSTYLA administered 2 to 3 times weekly. The regimen may be adjusted based on patient response. Pediatric population In children the recommended starting regimen is 20–50 international units/kg of AFSTYLA administered 2 to 3 times a week. Higher and/or more frequent dosing based on body weight may be needed because clearance (based on per kg body weight) has been shown to be higher in the pediatric population (0 to 12 years of age). Currently available data are described in section 5.2 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. Geriatric population Clinical studies of AFSTYLA did not include subjects aged over 65 years. Monitoring for inhibitors Patients should be monitored for the development of factor VIII inhibitors. See also section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. Method of administration Intravenous use. For instructions on reconstitution of the medicinal product before administration, see section 6.6 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. The reconstituted preparation should be injected slowly at a rate comfortable for the patient. The patient should be observed for any immediate reaction. If any reaction takes place that might be related to the administration of AFSTYLA, the rate of injection should be decreased or the application should be stopped, as required by the clinical condition of the patient (see also section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_).