Posology : מינונים

4.2   Posology and method of administration
Treatment should be under the supervision of a doctor 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 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 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 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. The activity of factor VIII in plasma is expressed either as percentage (relative to normal level 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 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 2 IU/dl. The required dose is determined using the following formula:

Required units = 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.

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. 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/Type of       FVIII level required (%)        Frequency of doses surgical procedure                  (IU/dl)                         (hours)/Duration of therapy (days) Haemorrhage

Early haemarthrosis, muscle bleeding 20–40                          Repeat every 12 to 24 hours, at or oral bleeding                                                    least 1 day, until the bleeding episode as indicated by pain is resolved or healing achieved


More extensive haemarthrosis,           30–60                       Repeat infusion every 12–24 hours muscle bleeding or haematoma                                        for 3–4 days or more until pain and acute disability are resolved


Life threatening haemorrhages           60–100                      Repeat infusion every 8 to 24 hours until threat is resolved

Surgery
Minor surgery including tooth           30–60                       Every 24 hours, at least 1 day,until extraction                                                          healing is achieved 
Major surgery                           80–100                      Repeat infusion every 8–24 hours (pre- and postoperative)    until adequate wound healing, then 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 recommended doses are 20–40 IU of factor VIII per kg body weight every second day or 20–50 IU of factor VIII per kg body weight 3 times weekly. In adults and adolesents (>12 years) with bleeding risk not greater than one episode a year or patients with low compliance to the higher frequency treatment, a less frequent regimen (40-60 IU/kg every third day or twice weekly) may be applicable. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

Surgery
There is no experience in surgery of paediatric patients.

Elderly
There is no experience in patients >65 years.
Paediatric population
For long term prophylaxis against bleeding in patients below the age of 12, doses of 25–50 IU of factor VIII per kg body weight every second day or 25–60 IU of factor VIII per kg body weight 3 times weekly are recommended. For paediatric patients above the age of 12 the dose recommendations are the same as for adults.

Method of administration
Intravenous use.

The recommended infusion rate for NovoEight is 1–2 ml/min. The rate should be determined by the patient’s comfort level.

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