Posology : מינונים

4.2   Posology and method of administration

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 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.

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 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.

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 1.5% to 2.5% of normal activity.
The required dose is determined using the following formulae:

Required units = body weight (kg) x desired factor VIII rise (% or IU/dL) x reciprocal of observed recovery (i.e. 0.5 for recovery of 2.0%).

The amount to be administered and the frequency of administration should always be targeted to the clinical effectiveness required in the individual case.

In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given level (in % of normal) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:


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

Prophylaxis
For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses for adolescents (≥ 12 years age) and adult patients are 20 to 40 IU of Kovaltry per kg body weight two to three times per week.
In some cases, especially in younger patients, shorter dose intervals or higher doses may be necessary.


Paediatric population
A safety and efficacy study has been performed in children of 0-12 years (see section 5.1); limited data are available for children below 1 year.
The recommended prophylaxis doses are 20-50 IU/kg twice weekly, three times weekly or every other day according to individual requirements. For paediatric patients above the age of 12, the dose recommendations are the same as for adults.

Method of administration

Intravenous use.
Kovaltry should be injected intravenously over 2 to 5 minutes depending on the total volume. The rate of administration should be determined by the patient’s comfort level (maximal rate of infusion: 2 mL/min).
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and the package leaflet.