Posology : מינונים

4.2        Posology and method of administration

Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia.


Previously untreated patients

The safety and efficacy of Esperoct in previously untreated patients have not yet been established.

Treatment monitoring

During the course of treatment, appropriate determination of factor VIII activity levels is advised to guide adjustments of the dosing regimen of Esperoct, if needed. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and incremental recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients. In the case of major surgical interventions in particular, monitoring of the factor VIII substitution therapy by measurement of plasma factor VIII activity is necessary.

The factor VIII activity of Esperoct can be measured using the conventional factor VIII assays, the chromogenic assay and the one-stage assay.
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.
When using a one-stage clotting assay some silica based reagents should be avoided as they cause underestimation. 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.

Posology

The dose, dosing interval and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of the bleeding, on the targeted factor VIII activity level and the patient’s clinical condition. The number of units of factor VIII administered is expressed in International Units (IU), which is related to the current WHO concentrate standard for factor VIII products. The activity of factor VIII in plasma is expressed either as percentage (relative to normal human plasma level) or in International Units per dL (relative to the current 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 human plasma.

On demand treatment and treatment of bleeding episodes

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:
Required units (IU) = body weight (kg) x desired factor VIII rise (%) (IU/dL) 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.

Guidance for the dosing of Esperoct for the on-demand treatment and treatment of bleeding episodes is provided in table 1. Plasma factor VIII activity levels should be maintained at or above the described plasma levels (in IU per dL or % of normal). For treatment of bleeds a maximum single dose of Esperoct at 75 IU/kg and a maximum total dose of 200 IU/kg/24 hours may be administered.

Table 1         Guidance for treatment of bleeding episodes with Esperoct Degree of haemorrhage Factor VIII level Frequency of Duration of therapy required (IU/dL doses (hours) or % of normal)a
Mild                      20-40               12-24           Until the bleeding is Early haemarthrosis, mild                                     resolved muscle bleeding or mild oral bleeding
Moderate                  30-60               12-24           Until the bleeding is More extensive                                                resolved haemarthrosis, muscle bleeding, haematoma
Severe or                 60-100              8-24            Until the threat is life-threatening                                              resolved haemorrhages a
The required dose is determined using the following formula:
Required units (IU) = body weight (kg) x desired factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL).

Perioperative management

The dose level and dosing intervals for surgery depend on the procedure and local practice. A maximum single dose of Esperoct at 75 IU/kg and a maximum total dose of 200 IU/kg/24 hours may be administered.
The frequency of doses and duration of therapy should always be individually adjusted based on individual clinical response.

Table 2 includes general recommendation for dosing of Esperoct for perioperative management.
Consideration should be given to maintain a factor VIII activity at or above the target range.

Table 2         Guidance for dosing of Esperoct for perioperative management Type of surgical Factor VIII       Frequency of doses (hours)     Duration of procedure          level required                                 therapy (%) (IU/dL)a
Minor surgery      30-60           Within one hour before         Single dose or repeat Including tooth                    surgery                        injection extraction                                                        every 24 hours for at Repeat after 24 hours if       least 1 day necessary                      until healing is achieved
Major surgery      80-100          Within one hour before         Repeat injection (pre- and       surgery to achieve factor VIII every 8 to post-           activity within the target     24 hours as operative)      range                          necessary until adequate wound
Repeat every 8 to 24 hours to healing is maintain factor VIII activity  achieved within the target range        Consider to continue therapy for another 7 days to maintain a
factor VIII activity of 30% to
60% (IU/dL) a
The required dose is determined using the following formula:
Required units (IU) = body weight (kg) x desired factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL).

Prophylaxis
Adults and adolescents (age 12 and over): The recommended dose is 50 IU of Esperoct per kg body weight every 4 days.

Adjustments of doses and administration intervals may be considered based on achieved factor VIII levels and individual bleeding tendency.

Paediatric population
The dose in adolescents (12 years and above) is the same as for adults.

Children (under 12): One dose of 65 IU (50-75 IU) Esperoct® per kg body weight is administered twice a week.


Method of administration
Esperoct is for intravenous use.

Esperoct should be administered by intravenous injection (over approximately 2 minutes) after reconstitution of the powder with 4 mL supplied solvent (sodium chloride 9 mg/mL (0.9%) solution for injection).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.