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.

Posology
The dosage 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 World Health Organisation (WHO) international standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or 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. The calculation of the required dosage 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 1.5% to 2% of normal. The required dosage is determined using the following formula:
Required units = body weight (kg) x desired factor VIII rise (%) (IU/dl) x 0.5 The amount and frequency of administration should always be adjusted according to the clinical effectiveness in the individual patient.

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 level     Frequency of doses (hours) / Duration Type of surgical procedure        required (%)                  of therapy (days) (IU/dl)
Haemorrhage
Early haemarthrosis, muscle                            Repeat every 12 to 24 hours. At least 1 bleeding or oral bleeding                              day, until the bleeding episode as 20 – 40 indicated by pain is resolved or healing is achieved.
More extensive haemarthrosis,                          Repeat infusion every 12 to 24 hours for 3 muscle bleeding or haematoma           30 – 60         to 4 days or more until pain and disability are resolved.
Life threatening haemorrhages                          Repeat infusion every 8 to 24 hours until 60 - 100 threat is resolved.
Surgery
Minor                                                  Every 24 hours, at least 1 day, until 30 – 60 including tooth extraction                             healing is achieved.
Major                                                  Repeat infusion every 8 to 24 hours until 80 – 100 adequate wound healing, then therapy for
(pre- and at least another 7 days to maintain a FVIII postoperative) activity of 30% to 60%.


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. In the case of major surgical interventions in particular, a precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable. Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives.
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.
Paediatric population
A clinical study which was conducted in 15 patients of 6 years of age or less did not identify any special dosage requirements for children.
Clinical data on the use of Octanate in previously untreated patients (PUPs) are limited (see section 4.8). Patients should be monitored for the development of factor VIII inhibitors. If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if a factor VIII inhibitor is present. In patients with high levels of inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of patients with haemophilia. See also 4.4.

Method of administration
For instructions on reconstitution of the medicinal product before administration, see section 6.6. The product should be administered via the intravenous route. It is recommended not to administer more than 2 - 3 ml per minute.