Posology : מינונים

4.2   Posology and method of administration

Posology
Only general dosage guidelines are given below. Treatment should be initiated under the supervision of a physician experienced in the treatment of coagulation disorders. The dosage and duration of the substitution therapy depend on the severity of the disorder, on the location and extent of bleeding and on the patient’s clinical condition.

The amount and the frequency of administration should be calculated on an individual patient basis. Dosage intervals must be adapted to the different circulating half-lives of the respective coagulation factors in the prothrombin complex (see section 5.2). Individual dosage requirements can only be identified on the basis of regular determinations of the individual plasma levels of the coagulation factors of interest, or on global tests of the prothrombin complex levels (INR, Quick’s test), and a continuous monitoring of the clinical condition of the patient.

In case of major surgical interventions, precise monitoring of the substitution therapy by means of coagulation assays is essential (specific coagulation factor assays and/or global tests for prothrombin complex levels).

- Bleeding and perioperative prophylaxis of bleedings during vitamin K antagonist treatment.

The dose will depend on the INR before treatment and the targeted INR. The pre- treatment INR should be measured as close as possible to the time of dosing in order to calculate the appropriate dose of Beriplex. In the following table approximate doses (ml/kg body weight of the reconstituted product and IU Factor IX/kg b.w.) required for normalisation of INR (e.g. ≤ 1.3) at different initial INR levels are given.

Pre-treatment INR                           2.0 – 3.9      4.0 – 6.0        > 6.0 Approximate dose ml/kg body weight              1             1.4             2 Approximate dose IU (Factor IX)/kg             25             35             50 body weight
Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, the maximum single dose (IU of Factor IX) should therefore not exceed 2500 IU for an INR of 2.0 - 3.9, 3500 IU for an INR of 4.0 - 6.0 and 5000 IU for an INR of > 6.0.
The correction of the vitamin K antagonist-induced impairment of haemostasis is commonly reached approximately 30 minutes after the injection.
The simultaneous administration of vitamin K should be considered in patients receiving Beriplex for urgent reversal of vitamin K antagonists since vitamin K usually takes effect within 4 - 6 hours. Repeated dosing with Beriplex for patients requiring urgent reversal of vitamin K antagonist treatment is not supported by clinical data and therefore not recommended.

These recommendations are based on data from clinical studies with a limited number of subjects. Recovery and the duration of effect may vary, therefore monitoring of INR during treatment is mandatory.


Paediatric population
The safety and efficacy of Beriplex in children and adolescents has not yet been established in controlled clinical studies (see section 4.4).

Older population

The posology and method of administration in older people (> 65 years) is equivalent to the general recommendations.


Method of administration
For instructions on reconstitution of the medicinal product before administration, see section 6.6. The reconstituted solution should be administered intravenously (not more than 3 IU/kg/minute, max. 210 IU/minute, approximately 8 ml/minute).