Posology : מינונים

4.2   Posology and method of administration
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.

Previously untreated patients
No data are available.

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 infusions. 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 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.

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.

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 1 % to 2 % of normal activity.

The required dose is determined using the following formula:

Required units = body weight (kg) x desired factor VIII rise (%) x 0.5 
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) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:

Degree of haemorrhage/               Factor VIII             Frequency of doses Type of surgical procedure           level required          (hours)/Duration of therapy (%)                     (days)
Haemorrhage
Early haemarthrosis, muscle         20 - 40                 Repeat every 12 to 24 hours. At bleeding or oral bleeding                                   least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.
More extensive                      30 - 60                 Repeat every 12 to 24 hours for haemarthrosis,                                              3 - 4 days or more until pain and muscle bleeding or                                          acute disability are resolved.
haematoma
Life threatening                    60 - 100                Repeat every 8 to 24 hours until haemorrhages                                                threat is resolved.

Surgery
Minor surgery                       30 - 60                 Every 24 hours, at least 1 day, including tooth extraction                                  until healing is achieved.
Major surgery                       80 - 100                Repeat every 8 to 24 hours until (pre- and post-         adequate wound healing, then operative)              therapy for at least another 7 days to maintain a factor VIII activity of 30 - 60%.

Prophylaxis
For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.
There are insufficient data to recommend the use of Haemoctin SDH 250, 500 or 1000 in children less than 6 years of age.


Method of administration
Intravenous use. It is recommended not to administer more than 2 - 3 ml Haemoctin SDH/ min.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.