Posology : מינונים

4.2       Posology and method of administration

Therapy with Recormon should be initiated by physicians experienced in the above mentioned indications. As anaphylactoid reactions were observed in isolated cases, it is recommended that the first dose be administered under medical supervision.

Posology
Treatment of anemic patients with chronic renal failure

In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, RECORMON dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose of RECORMON sufficient to reduce the need for RBC transfusions [see Warnings and Precautions].

Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events.

Anemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary. Recormon should be administered either subcutaneously or intravenously in order to increase haemoglobin to not greater than 11 g/dl.
Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid puncture of peripheral veins. In case of intravenous administration, the solution should be injected over approx. 2 minutes, e.g. in haemodialysis patients via the arterio-venous fistula at the end of dialysis.

For patients with Chronic Renal Failure on dialysis:

-        Initiate RECORMON treatment when the hemoglobin level is less than 10 g/dL.
-        If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of RECORMON 
For patients with Chronic Renal Failure not on dialysis:

Consider initiating RECORMON treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:

-     The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and, reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.

-    If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of RECORMON, and use the lowest dose of RECORMON sufficient to reduce the need for RBC transfusions.

Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) to 11 g/dl (6.83 mmol/I).
A sustained haemoglobin level of greater than 11 g/dl should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 11 g/dl are observed are described below.

A rise in haemoglobin of greater than 2 g/dl (1.25 mmol/l) over a four week period should be avoided. If it occurs, appropriate dose adjustment should be made as provided. If the rate of rise in haemoglobin is greater than 2 g/dl (1.25 mmol/l) in one month or if the haemoglobin level is increasing and approaching 11 g/dl the dose is to be reduced by approximately 25 %. If the haemoglobin level continues to increase, therapy should be interrupted until the hemoglobin level begins to decrease, at which point therapy should be restarted at a dose approximately 25 % below the previously administered dose.

Patients should be monitored closely to ensure that the lowest approved effective dose of Recormon is used to provide adequate control of the symptoms of anemia whilst maintaining a haemoglobin concentration below or at 11 g/dl.

Caution should be exercised with escalation of Recormon doses in patients with chronic renal failure. In patients with a poor haemoglobin response to Recormon, alternative explanations for the poor response should be considered (see sections 4.4 and 5.1).

In the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral vascular diseases, the weekly increase in Hb and the target Hb should be determined individually taking into account the clinical picture.

Treatment with Recormon is divided into two stages.

1.    Correction phase
-     Subcutaneous administration:
The initial dosage is 3 x 20 IU/kg body weight per week. The dosage may be increased every 4 weeks by 3 x 20 IU/kg and week if the increase of Hb is not adequate (< 0.25 g/dl per week).
The weekly dose can also be divided into daily doses.
-     Intravenous administration:
The initial dosage is 3 x 40 IU/kg per week. The dosage may be raised after 4 weeks to 80 IU/kg - three times per week - and by further increments of 20 IU/kg if needed, three times per week, at monthly intervals.
For both routes of administration, the maximum dose should not exceed 720 IU/kg per week.

2.    Maintenance phase
To maintain an Hb of between 10 and 11 g/dl, the dosage is initially reduced to half of the previously administered amount. Subsequently, the dose is adjusted at intervals of one or two weeks individually for the patient (maintenance dose).

In the case of subcutaneous administration, the weekly dose can be given as one injection per week or in divided doses three or seven times per week. Patients who are stable on a once weekly dosing regimen may be switched to once every two weeks administration. In this case dose increases may be necessary.

Results of clinical studies in children have shown that, on average, the younger the patients, the higher the Recormon doses required. Nevertheless, the recommended dosing schedule should be followed as the individual response cannot be predicted.

Treatment with Recormon is normally a long-term therapy. It can, however, be interrupted, if necessary, at any time. Data on the once weekly dosing schedule are based on clinical studies with a treatment duration of 24 weeks.



Treatment of chemotherapy-induced anemia in cancer patients:

Recormon should be administered by the subcutaneous route to patients with anemia (e.g. haemoglobin concentration ≤ 10g/dl (6.2 mmol/l)). Anemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.

The weekly dose can be given as one injection per week or in divided doses 3 to 7 times per week.

The recommended initial dose is 30,000 IU per week (corresponding to approximately 450 IU/kg body weight per week, based on an average weighted patient).

Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.2 mmol/l) to 11 g/dl (6.83 mmol/l).
A sustained haemoglobin level of greater than 11 g/dl should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 11 g/dl are observed are described below.

If, after 4 weeks of therapy, the haemoglobin value has increased by at least 1 g/dl (0.62 mmol/l), the current dose should be continued. If the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l), a doubling of the weekly dose should be considered. If, after 8 weeks of therapy, the haemoglobin value has not increased by at least 1 g/dl (0.62 mmol/l), response is unlikely and treatment should be discontinued.
The therapy should be continued up to 4 weeks after the end of chemotherapy.

The maximum dose should not exceed 60,000 IU per week.

Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50 % in order to maintain haemoglobin at that level. Appropriate dose titration should be considered.

If the haemoglobin exceeds 11 g/dl the dose should be reduced by approximately 25 to 50 %. Treatment with Recormon should be temporarily discontinued if haemoglobin levels exceed 13 g/dl (8.1 mmol/l). Therapy should be reinitiated at approximately 25 % lower than the previous dose after haemoglobin levels fall to 11 g/dl or below.

If the rise in haemoglobin is greater than 2 g/dl (1.3 mmol/l) in 4 weeks, the dose should be reduced by 25 to 50 %.

Patients should be monitored closely to ensure that the lowest approved dose of Recormon is used to provide adequate control of the symptoms of anemia.

Treatment for increasing the amount of autologous blood:
The solution is administered intravenously over approx. 2 minutes or subcutaneously.
Recormon is administered twice weekly over 4 weeks. On those occasions where the patient's PCV allows blood donation, i.e. PCV  33 %, Recormon is administered at the end of blood donation.
During the entire treatment period, a PCV of 48 % should not be exceeded.

The dosage must be determined by the surgical team individually for each patient as a function of the required amount of pre-donated blood and the endogenous red cell reserve:
1.    The required amount of pre-donated blood depends on the anticipated blood loss, use of blood conserving procedures and the physical condition of the patient.
This amount should be that quantity which is expected to be sufficient to avoid homologous blood transfusions.
The required amount of pre-donated blood is expressed in units whereby one unit in the nomogram is equivalent to 180 ml red cells.
2.    The ability to donate blood depends predominantly on the patient's blood volume and baseline PCV. Both variables determine the endogenous red cell reserve, which can be calculated according to the following formula.

Endogenous red cell reserve = blood volume [ml] x (PCV - 33) ÷ 100
Women: blood volume [ml] = 41 [ml/kg] x body weight [kg] + 1200 [ml]
Men:     blood volume [ml] = 44 [ml/kg] x body weight [kg] + 1600 [ml] (body weight  45 kg)

The indication for treatment with Recormon and, if given, the single dose should be determined from the required amount of pre-donated blood and the endogenous red cell reserve according to the following graphs.



Female patients                                          Male patients Required amount of pre-donated blood           Required amount of pre-donated blood [units]                                        [units]



Endogenous red cell reserve [ml]                Endogenous red cell reserve [ml] 
The single dose thus determined is administered twice weekly over 4 weeks. The maximum dose should not exceed 1600 IU/kg body weight per week for intravenous or 1200 IU/kg per week for subcutaneous administration.

Method of administration
The Recormon pre-filled syringe is ready for use. Only solutions which are clear or slightly opalescent, colourless and practically free of visible particles may be injected.
Recormon in pre-filled syringe is a sterile but unpreserved product. Under no circumstances should more than one dose be administered per syringe; the medicinal product is for single use only.