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 and/or bleeding disorders.

In the management of severe postpartum haemorrhage, appropriate multidisciplinary expertise should be consulted. In addition to obstetricians, this includes anaesthesiologists, critical care specialists and/or haematologists. Standard management practices should remain implemented, based on the individual patient’s requirements. Maintenance of adequate fibrinogen concentration and platelet count is recommended in order to optimise the benefit of NovoSeven RT treatment.

Posology

Haemophilia A or B with inhibitors or expected to have a high anamnestic response 
Dose
NovoSeven RT should be given as early as possible after the start of a bleeding episode. The recommended initial dose, administered by intravenous bolus injection, is 90 µg per kg body weight.
Following the initial dose of NovoSeven RT further injections may be repeated. The duration of treatment and the interval between injections will vary with the severity of the haemorrhage, the invasive procedures or surgery being performed.

Paediatric population
Current clinical experience does not warrant a general differentiation in dosing between children and adults, although children have faster clearance than adults. Therefore, higher doses of rFVIIa may be needed in paediatric patients to achieve similar plasma concentrations as in adult patients (see section 5.2).

Dose interval
Initially 2–3 hours to obtain haemostasis.
If continued therapy is needed, the dose interval can be increased successively once effective haemostasis is achieved to every 4, 6, 8 or 12 hours for as long as treatment is judged as being indicated.

Mild to moderate bleeding episodes (including home therapy)
Early intervention has been shown to be efficacious in the treatment of mild to moderate joint, muscle and mucocutaneous bleeds. Two dosing regimens can be recommended:

1)    Two to three injections of 90 µg per kg body weight administered at three-hour intervals.
If further treatment is required, one additional dose of 90 µg per kg body weight can be administered.
2)    One single injection of 270 µg per kg body weight.

The duration of home therapy should not exceed 24 hours. Only after consultation with the haemophilia treatment centre can continued home treatment be considered.

There is no clinical experience with administration of a single dose of 270 µg per kg body weight in elderly patients.

Serious bleeding episodes
An initial dose of 90 µg per kg body weight is recommended and could be administered on the way to the hospital where the patient is usually treated. The following dose varies according to the type and severity of the haemorrhage. Dosing frequency should initially be every second hour until clinical improvement is observed. If continued therapy is indicated, the dose interval can then be increased to 3 hours for 1–2 days. Thereafter, the dose interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged as being indicated. A major bleeding episode may be treated for 2–3 weeks but can be extended beyond this if clinically warranted.
Invasive procedure/surgery
An initial dose of 90 µg per kg body weight should be given immediately before the intervention. The dose should be repeated after 2 hours and then at 2–3 hour intervals for the first 24–48 hours depending on the intervention performed and the clinical status of the patient. In major surgery, the dose should be continued at 2–4 hour intervals for 6–7 days. The dose interval may then be increased to 6–8 hours for another 2 weeks of treatment. Patients undergoing major surgery may be treated for up to 2–3 weeks until healing has occurred.

Acquired Haemophilia

Dose and dose interval
NovoSeven RT should be given as early as possible after the start of a bleeding episode. The recommended initial dose, administered by intravenous bolus injection, is 90 µg per kg body weight.
Following the initial dose of NovoSeven RT further injections may be given if required. The duration of treatment and the interval between injections will vary with the severity of the haemorrhage, the invasive procedures or the surgery being performed.
The initial dose interval should be 2–3 hours. Once haemostasis has been achieved, the dose interval can be increased successively to every 4, 6, 8 or 12 hours for as long as treatment is judged to be indicated.

Factor VII deficiency

Dose, dose range and dose interval
The recommended dose range in adults and children for treatment of bleeding episodes and for the prevention of bleeding in patients undergoing surgery or invasive procedures is 15–30 μg per kg body weight every 4–6 hours until haemostasis is achieved. Dose and frequency of injections should be adapted to each individual.

Paediatric population
Limited clinical experience in long term prophylaxis has been gathered in the paediatric population below 12 years of age, with a severe clinical phenotype (see section 5.1).

Dose and frequency of injections for prophylaxis should be based on clinical response and adapted to each individual.

Glanzmann’s thrombasthenia

Dose, dose range and dose interval
The recommended dose for treatment of bleeding episodes and for the prevention of bleeding in patients undergoing surgery or invasive procedures is 90 µg (range 80-120 µg) per kg body weight at intervals of two hours (1.5-2.5 hours). At least three doses should be administered to secure effective haemostasis. The recommended route of administration is bolus injection as lack of efficacy may appear in connection with continuous infusion.

For those patients who are not refractory, platelets is the first line treatment for Glanzmann’s thrombasthenia.

Severe postpartum haemorrhage
Dose range and dose interval
The recommended dose range for the treatment of bleeding is 60 – 90 μg per kg body weight administered by intravenous bolus injection. Peak coagulant activity can be expected at 10 minutes. A second dose can be administered based on clinical response of the individual patient.
It is recommended that in case of insufficient haemostatic response, a second dose can be administered after 30 minutes.


Method of administration

For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Administer the solution as an intravenous bolus injection over 2- 5 minutes.

Monitoring of treatment – laboratory tests
There is no requirement for monitoring of NovoSeven RT therapy. Severity of bleeding condition and clinical response to NovoSeven RT administration must guide dosing requirements.

After administration of rFVIIa, prothrombin time (PT) and activated partial thromboplastin time (aPTT) have been shown to shorten, however no correlation has been demonstrated between PT and aPTT and clinical efficacy of rFVIIa.