ADYNOVATE 3000 IU POWDER AND SOLVENT FOR SOLUTION FOR INJECTION

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**2 DOSAGE AND ADMINISTRATION** **For intravenous use after reconstitution only.** **2.1 Dose** - One international unit corresponds to the activity of factor VIII contained in one millilitre of normal human plasma. - Dosage and duration of treatment depend on the severity of factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful monitoring of replacement therapy is necessary in cases of serious or life-threatening bleeding episodes. - Potency assignment is determined using a one-stage clotting assay. Plasma factor VIII levels can be monitored clinically using a one-stage clotting assay. - Calculate the dose of ADYNOVATE based on the empirical finding that one international unit of ADYNOVATE per kg body weight increases the plasma factor VIII level by 2 international units per dL of plasma. Use the following formula to estimate the expected _in vivo_ peak increase in factor VIII level expressed as international units per dL (or % of normal) and the dose to achieve a desired _in vivo_ peak increase in factor VIII level:   - Patients vary in their pharmacokinetic (e.g., clearance, half-life, _in vivo_ recovery) and clinical response. Base the dose and frequency of ADYNOVATE on the individual clinical response. On-demand Treatment and Control of Bleeding Episodes A guide for dosing of ADYNOVATE for the on-demand treatment and control of bleeding episodes is provided in Table 1. Maintain plasma factor VIII activity level at or above the described plasma levels (in international units per dL or % of normal).  Perioperative Management A guide for dosing ADYNOVATE during surgery (perioperative management) is provided in Table 2. Consideration should be given to maintain a factor VIII activity at or above the target range.  Routine Prophylaxis Administer 40–50 international units per kg body weight 2 times per week in children and adults (12 years and older). Administer 55 international units per kg body weight 2 times per week in children (< 12 years) with a maximum of 70 international units per kg. Adjust the dose and dosing intervals based on the patient’s clinical response. **2.2 Preparation and Reconstitution** Preparation and reconstitution using the BAXJECT II Hi-Flow device For reconstitution, use only the diluent vial and the reconstitution device provided in the pack. 1. Use antiseptic technique (clean and germ-free conditions) and a flat work surface during the reconstitution procedure. 2. Allow the vials of ADYNOVATE and diluent to reach room temperature (between 15 °C and 25 °C) before use. 3. Remove plastic caps from the ADYNOVATE and diluent vials. 4. Clean rubber stoppers with an alcohol swab and allow to dry prior to use. 5. Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package. 6. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B). 7. Grip the BAXJECT II Hi-Flow package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II Hi-Flow device. Do not touch the exposed purple plastic spike. 8. Turn the system over so that the diluent vial is on top. Quickly insert the purple plastic spike fully into the ADYNOVATE vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the ADYNOVATE vial. 9. Swirl gently until the ADYNOVATE is completely dissolved. Do not shake. Do not refrigerate after reconstitution.  Preparation and reconstitution using the BAXJECT III system Preparation - Do not remove ADYNOVATE or diluent vials from the external housing. - Examine the packaging containing ADYNOVATE to ensure no damage or peeling of the lid is evident. Do not use if the lid is not completely sealed on the blister. - Use aseptic technique (clean and germ-free) and a flat work surface during the reconstitution procedure. Reconstitution 1. Allow the ADYNOVATE package to reach room temperature (between 15°C and 25°C) before use. 2. Wash your hands thoroughly using soap and warm water. 3. Open the package by peeling away the lid. Remove the BAXJECT III system from the package. 4. Place ADYNOVATE on a flat surface with the diluent vial on top (Figure E). The diluent vial has a blue stripe. Do not remove the blue cap until instructed in a later step. 5. With one hand holding ADYNOVATE in the BAXJECT III system, press down firmly on the diluent vial with the other hand until the system is fully collapsed and the diluent flows down into the ADYNOVATE vial (Figure F). Do not tilt the system until the transfer is complete. 6. Verify the diluent transfer is complete. Swirl gentle until all material is dissolved (Figure G). Do not shake. Be sure that the ADYNOVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute). After reconstitution, the solution should be clear, colourless and free from foreign particles. Do not refrigerate after reconstitution.  **Administration** - Visually inspect the reconstituted solution for particulate matter and discolouration prior to administration. - The appearance of the reconstituted solution is clear and colourless. - Do not use if particulate matter or discolouration is observed. - Administer as soon as possible, but no later than 3 hours after reconstitution. Administration steps for BAXJECT II Hi-Flow device 1. Remove the blue cap from the BAXJECT II Hi-Flow device (Figure H). Connect the syringe to the BAXJECT II Hi-Flow device. Use of a Luer-lock syringe is recommended. **Do not inject air.** 2. Turn the system upside down (ADYNOVATE vial now on top). Draw the reconstituted solution into the syringe by pulling the plunger back slowly (Figure I). 3. Disconnect the syringe; attach the infusion set needle to the syringe and inject the reconstituted solution intravenously. If a patient is to receive more than one vial of ADYNOVATE, the contents of multiple vials may be drawn into the same syringe. A separate BAXJECT II Hi-Flow device is required to reconstitute each vial of ADYNOVATE with the diluent. 4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  Administration steps for BAXJECT III system: 1. Remove the blue cap from the BAXJECT III system. Connect the syringe to the system (Figure J). Use of a Luer-lock syringe is recommended. **Do not inject air**. 2. Turn the system upside down (ADYNOVATE vial now on top). Draw the reconstituted solution into the syringe by pulling plunger back slowly (Figure K). 3. Disconnect the syringe, attach the infusion set needle to the syringe, and inject the reconstituted solution intravenously. If a patient is to receive more than one vial of ADYNOVATE, the contents of multiple vials may be drawn into the same syringe. 4. Administer ADYNOVATE intravenously over a period of less than or equal to 5 minutes (maximum infusion rate 10 mL per min).  It is strongly recommended that every time ADYNOVATE is administered, the name and batch number of the product are recorded. Peel-off labels are provided on the ADYNOVATE vial (with BAXJECT II Hi-Flow device) and on the blister (with BAXJECT III system).