Posology : מינונים

4.2    Posology and method of administration

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.
Previously untreated patients
The safety and efficacy of Refixia in previously untreated patients have not yet been established.
Treatment monitoring
Routine monitoring of factor IX activity levels for the purpose of dose adjustment is not necessary. In the clinical trial programme, dose adjustment was not performed. Mean steady state factor IX trough levels above 15% were observed for all age groups, see section 5.2 for details.

Due to the interference of polyethylene glycol (PEG) in the one-stage clotting assay with various aPTT reagents, it is recommended to use a chromogenic assay (e.g. Rox Factor IX or Biophen) when monitoring is needed. If a chromogenic assay is not available, it is recommended to use a one-stage clotting assay with an aPTT reagent (e.g. Cephascreen) qualified for use with Refixia. For modified long-acting factor products, it is known that the one-stage clotting assay results are highly dependent on the aPTT reagent and reference standard used. For Refixia, some reagents will cause underestimation (30–50%), while most silica containing reagents will cause severe overestimation of the factor IX activity (more than 400%). Therefore, silica based reagents should be avoided. Use of a reference laboratory is recommended when a chromogenic assay or a qualified one-stage clotting assay is not available locally.

Posology
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).

Prophylaxis
40 IU/kg body weight once weekly.
Adjustments of doses and administration intervals may be considered based on achieved FIX levels and individual bleeding tendency. The trough levels achieved with the weekly 40 IU/kg dosing regimen are summarised in section 5.2.

Patients on prophylaxis who forget a dose are advised to take their dose upon discovery and thereafter continue with the usual once weekly dosing schedule. A double dose should be avoided.

On-demand treatment
Dose and duration of the substitution therapy depend on the location and severity of the bleeding, see Table 1 for dosing guidance in bleeding episodes.



Table 1      Treatment of bleeding episodes with Refixia
Degree of              Recommended           Dosing recommendations haemorrhage            dose IU/kg of
Refixia

Early                  40                    A single dose is recommended.
haemarthrosis,
muscle bleeding or oral bleeding.
More extensive haemarthrosis,
muscle bleeding or haematoma.

Severe or life         80                    Additional doses of 40 IU/kg can be threatening                                  given.

haemorrhages.


Surgery
The dose level and dosing intervals for surgery depend on the procedure and local practice. General recommendations are provided in Table 2.

Table 2      Treatment in surgery with Refixia
Type of surgical          Recommended          Dosing recommendations procedure                 dose IU/kg body weight

Minor surgery             40                   Additional doses can be given if needed.
including tooth extraction.

Major surgery.            80                   Pre-operative dose.

40                   Consider two repeated doses of 40 IU/kg
(in 1–3 day intervals) within the first week after surgery.

Due to the long half-life of Refixia, the frequency of dosing in the post-surgical period may be extended to once weekly after the first week until bleeding stops and healing is achieved.
Children and adolescents
The same dose is recommended for children as for adults: 40 IU/kg body weight.

Method of administration
Intravenous use.

Refixia is administered by intravenous bolus injection over several minutes after reconstitution of the powder for injection with the histidine solvent. The rate of administration should be determined by the patient’s comfort level up to a maximum injection rate of 4 ml/min.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

In case of self-administration or administration by caregiver appropriate training is needed.