Afstyla Dosage/Direction for Use

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.
Treatment monitoring: During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated injections. Individual patients may vary in their responses to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight 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.
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients' blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagents used in the assay.
Plasma factor VIII activity in patients receiving AFSTYLA using either the chromogenic assay or the one-stage clotting assay should be monitored to guide the dose administered and the frequency of repeat injections. The chromogenic assay result most accurately reflects the clinical hemostatic potential of AFSTYLA and is preferred. The one-stage clotting assay result underestimates the factor VIII activity level compared to the chromogenic assay result by approximately 45%. If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the patient's factor VIII activity level.
Posology: 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 International Units (IU), which are 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 International Units (relative to an 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.
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.
On demand treatment: The calculation of the required dose 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 2 IU/dl. The required dose is determined 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.
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) within the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery: See Table 3.

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Prophylaxis: The recommended starting regimen is 20 to 50 IU/kg of AFSTYLA administered 2 to 3 times weekly. The regimen may be adjusted based on patient response.
Paediatric population: The recommended starting regimen in children (0 to <12 years of age) is 30 to 50 IU per kg of AFSTYLA administered 2 to 3 times weekly. More frequent or higher doses may be required in children <12 years of age to account for the higher clearance in this age group.
For adolescents of 12 years of age and above, the dose recommendations are the same as for adults (please refer to PHARMACOLOGY: Pharmacokinetics under Actions).
Elderly: Clinical studies of AFSTYLA did not include subjects over 65 years of age.
Method of administration: Intravenous use.
The reconstituted preparation should be injected slowly at a rate comfortable for the patient at a maximum injection rate of 10 ml/min.
For instructions on reconstitution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.