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.


Posology

The dosage and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the location and extent of the bleeding and on the patient’s clinical condition.

On demand treatment
The number of units of factor IX administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products. Factor IX 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 IX in plasma).
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of normal human plasma. The calculation of the required dosage of factor IX is based on the empirical finding that 1 International Unit (IU) factor IX per kg body weight raises the plasma factor IX activity by 1 % of normal activity. The required dosage is determined using the following formula:

Required units = body weight (kg) x desired factor IX rise (%) (IU/dl) x 0.8 
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case. Factor IX products rarely require to be administered more than once daily.

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

Degree of haemorrhage /              Factor IX level Frequency of doses (hours) / Type of surgical procedure            required (%) Duration of therapy (days) (IU/dl)
Haemorrhage
Early haemarthrosis,                      20 - 40     Repeat every 24 hours. At least 1 day, until muscle bleeding or oral                               the bleeding episode as indicated by pain is bleeding                                              resolved or healing is achieved.
More extensive haemarthrosis,             30 - 60     Repeat infusion every 24 hours for 3 - 4 muscle bleeding or haematoma                          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                             30 - 60     Every 24 hours, at least 1 day, until healing including tooth extraction                            is achieved.
Major Surgery                            80 – 100     Repeat infusion every 8-24 hours until (pre-/post-   adequate wound healing, then therapy for at operative)    least another 7 days to maintain a factor IX activity of 30% to 60% (IU/dl).


During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor IX activity) is indispensable. Individual patients may vary in their response to factor IX, achieving different levels of in-vivo recovery and demonstrating different half-lives.

Prophylaxis
For long term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses are 20 to 40 IU of factor IX per kilogram of body weight at intervals of 3 to 4 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

In the study conducted in 25 children under 6 years of age, the median dose administered per exposure day was similar for prophylaxis and treatment of bleeding, i.e. 35 to 40 IU/kg BW.

Patients should be monitored for the development of factor IX inhibitors. If the expected factor IX activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if a factor IX inhibitor is present.
In patients with high levels of inhibitor, factor IX therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of patients with haemophilia.
See also 4.4.

There is not enough data available to recommend continuous infusion of Octanine F in surgical procedures.

Method of administration

Dissolve the preparation as described at 6.6. The product should be administered via the intravenous route. It is recommended not to administer more than 2 - 3 ml per minute.