Adynovate Dosage/Direction for Use

Treatment with ADYNOVATE should be under the supervision of a physician experienced in the treatment of haemophilia.
Previously untreated patients: The safety and efficacy of ADYNOVATE in previously untreated patients have not yet been established. No data are available.
Treatment monitoring: During the course of treatment, appropriate determination of factor VIII levels (by one-stage clotting or chromogenic assays) is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on body weight may require adjustment in underweight or overweight patients. 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.
Dosage: The dose and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of the bleeding and on the patient's clinical condition.
The number of units of factor VIII administered is expressed in IU, which is related to the current WHO concentrate standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in IU (relative to an International Standard for factor VIII in plasma).
One IU of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human plasma.
On-demand treatment: The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/dL. The required dose is determined using the following formula: See equation.

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The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level (in % of normal or IU/dL) in the corresponding period.
The following table can be used to guide dosing in bleeding episodes and surgery: See Table 10.

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Prophylaxis: For long-term prophylaxis, the recommended dose is 40 to 50 IU per kg body weight of ADYNOVATE twice weekly in 3- to 4-day intervals. Dose and/or frequency should be adjusted to provide the necessary coverage to prevent bleeding. In some cases, doses up to 60 IU per kg can be used.
Paediatric population: On-demand treatment dosing in paediatric patients (<12 years of age) does not differ from adult patients. Higher doses or more frequent dosing may be required in some children.
For prophylactic therapy in patients under the age of 12, the recommended dose is 40 to 60 IU per kg body weight of ADYNOVATE twice weekly in 3- to 4-day intervals. In some cases, doses up to 80 IU per kg can be used.
Method of administration: ADYNOVATE should be administered via the intravenous route.
ADYNOVATE should be administered at room temperature not more than 3 hours after reconstitution.
Reconstituted products should be visually inspected for particulate matter and discolouration prior to administration. The solution should be clear to colourless. Do not administer if particulate matter or discolouration or cloudiness is found.
ADYNOVATE does not contain antimicrobial preservative. It is for single use in one patient only. Discard any residue.
The rate of administration should be determined to ensure the comfort of the patient up to a maximum of 10 mL/min.
After reconstitution, the solution is clear, colourless, free from foreign particles and has a pH of 6.7 to 7.3. The osmolality is ≥380 mOsmol/kg.
Preparation and reconstitution: Use aseptic technique.
Using the BAXJECT III system: Do not use if the lid is not completely sealed on the blister.
1. If the product is still stored in a refrigerator, take the sealed blister (contains powder and diluent vials preassembled with the system for reconstitution) from the refrigerator and let it reach room temperature.
2. Wash hands thoroughly using soap and warm water.
3. Open the ADYNOVATE package by peeling away the lid. Remove the BAXJECT III system from the blister.
4. Place ADYNOVATE on a flat surface with the diluent vial on top. 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. Do not tilt the system until the transfer is complete.
6. Verify that the diluent transfer is complete. Swirl gently until all material is dissolved. 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.
Administration: Remove the blue cap from the BAXJECT III device. Connect the syringe to the BAXJECT III device. Use of a Luer-lock syringe is recommended. Do not inject air.
Turn the system upside down (ADYNOVATE vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly.
Disconnect the syringe; attach a suitable needle and inject 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.
Administer ADYNOVATE over a period of less than or equal to 5 minutes (maximum infusion rate 10 mL per min).