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.

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

Posology
On demand treatment

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. Factor VIII 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 VIII in plasma).

One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human plasma. The calculation of the required dosage of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2.2% - 2.7% of normal activity (2.2-2.7 IU/dL).
The required dosage is determined using the following formula:


Required units =         body weight (kg) x desired factor VIII         x            0.4 rise (%) (IU/dL)

The amount to be administered and the frequency of administration should always be orientated 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; IU/dL) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:

Degree of haemorrhage / Type of           Factor VIII level      Frequency of doses (hours)/ surgical procedure                            required           Duration of therapy (days) (%)(IU/dL)
Haemorrhage
Early haemarthrosis, muscle                     20-40            Repeat every 12 to 24 hours. At bleeding or oral bleeding                                        least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.
More extensive haemarthrosis,                   30-60            Repeat infusion every 12-24 muscle bleeding or haematoma.                                    hours 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 resolved.
Surgery
Minor surgery                                  30-60           Every 24 hours, at least Including tooth extraction                                     1 day, until healing is achieved.

Major surgery                                 80-100           Repeat infusion every 8-24 (pre- and         hours until adequate wound postoperative)      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 doses are 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

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 infusions. 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.
Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives.


Paediatric patients
Optivate is indicated for use in children, including those less than 6 years of age. The usual dose is 17 to 30 IU/kg. This can be given up to 3 times a week to prevent bleeding. In the clinical trials the median doses in children ≤6 years of age were 24.7 IU/kg for routine prophylaxis and 27.6 IU/kg to treat a bleed.
Patients should be monitored for the development of factor VIII inhibitors. If the expected factor VIII 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 VIII inhibitor is present. In patients with high levels of inhibitor, factor VIII 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 section 4.4.

Method of administration
Dissolve the preparation as described in section 6.6. The product should be administered via the intravenous route at a rate not exceeding 3 mL per minute (note that increasing the rate of administration may result in side effects).