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.

ELOCTA can be used for all age groups.

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 injections.
Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight and 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 the 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 reagent used in the assay.

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 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 IU (relative to an International Standard for factor VIII in plasma).

One IU of recombinant factor VIII Fc 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 recombinant factor VIII Fc 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:

Required units = body weight (kg) × desired factor VIII rise (%) (IU/dL) × 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) in the corresponding period. Table 1 can be used to guide dosing in bleeding episodes and surgery:

Table 1: Guide to ELOCTA dosing for treatment of bleeding episodes and surgery 
Degree of haemorrhage /          Factor VIII level             Frequency of doses (hours)/ Duration of Type of surgical procedure       required (%) (IU/dL)          therapy (days) Haemorrhage
Early haemarthrosis, muscle      20-40                         Repeat injection every 12 to 24 hours for at bleeding or oral bleeding                                      least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved. 1

More extensive                   30-60                         Repeat injection every 12 to 24 hours for 3-4 haemarthrosis, muscle                                          days or more until pain and acute disability bleeding or haematoma                                          are resolved. 1 
Life threatening                 60-100                        Repeat injection every 8 to 24 hours until haemorrhages                                                   threat is resolved.

Surgery
Minor surgery including          30-60                         Repeat injection every 24 hours, for at least 1 tooth extraction                                               day, until healing is achieved.

Major surgery                    80-100                        Repeat injection every 8 to 24 hours as (pre- and post-               necessary until adequate wound healing, then operative)                    therapy at least for another 7 days to maintain a factor VIII activity of 30% to 60% (IU/dL).
1
In some patients and circumstances the dosing interval can be prolonged up to 36 hours. See section 5.2 for pharmacokinetic data.

Prophylaxis
For long term prophylaxis, the recommended dose is 50 IU of factor VIII per kg body weight at intervals of 3 to 5 days. The dose may be adjusted based on patient response in the range of 25 to 65 IU/kg (see section 5.1 and 5.2).
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

Elderly
There is limited experience in patients ≥65 years.

Paediatric population
For children below the age of 12, more frequent or higher doses may be required (see section 5.1). For adolescents of 12 years of age and above, the dose recommendations are the same as for adults.

Method of administration
ELOCTA is for intravenous use.

ELOCTA should be injected intravenously over several minutes. The rate of administration should be determined by the patient’s comfort level and should not exceed 10 mL/min.

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