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 the 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-life of the different 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 (prothrombin time, INR), and 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 bleeding during vitamin K antagonist treatment:

The dose will depend on the INR before treatment and the targeted INR. In the following table approximate doses (mL/kg body weight of the reconstituted product) required for normalisation of INR ( 1.2 within 1 hour) at different initial INR levels are given.
Initial INR                       2 – 2.5          2.5 – 3        3 – 3.5         > 3.5 

Approximate dose*
(mL Octaplex 500 IU               0.9 –1.3         1.3 – 1.6      1.6 – 1.9       > 1.9 /kg body weight)


*The single dose should not exceed 3000 IU (120 mL Octaplex 500 IU).

The correction of the vitamin K antagonist induced impairment of haemostasis persists for approximately 6-8 hours. However, the effects of vitamin K, if administered simultaneously, are usually achieved within 4-6 hours. Thus, repeated treatment with human prothrombin complex is not usually required when vitamin K has been administered.

As these recommendations are empirical and recovery and the duration of effect may vary, monitoring of INR during treatment is mandatory.

Bleeding and perioperative prophylaxis in congenital deficiency of the vitamin K dependent coagulation factors II and X when specific coagulation factor product is not available:

The calculated required dosage for treatment is based on the empirical finding that approximately 1 IU of factor II or X per kg body weight raises the plasma factor II or X activity by 0.02 and 0.017 IU/mL, respectively.

The dose of a specific factor administered is expressed in International Units (IU), which are related to the current WHO standard for each factor. The activity in plasma of a specific coagulation factor is expressed either as a percentage (relative to normal plasma) or in International Units (relative to the international standard for the specific coagulation factor).

One International Unit (IU) of a coagulation factor activity is equivalent to the quantity in one mL of normal human plasma.

For example, the calculation of the required dosage of factor X is based on the empirical finding that 1 International Unit (IU) of factor X per kg body weight raises the plasma factor X activity by 0.017 IU/mL. The required dosage is determined using the following formula: 
Required units = body weight (kg) x desired factor X rise (IU/mL) x 59  where 59 (mL/kg) is the reciprocal of the estimated recovery.

Required dosage for factor II:
Required units = body weight (kg) x desired factor II rise (IU/mL) x 50 

If the individual recovery is known, that value should be used for calculation.

Method of administration
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Octaplex 500 IU must be administered intravenously. The infusion should start at a speed of 1 mL per minute, followed by 2-3 mL per minute, using an aseptic technique.