Posology : מינונים

4.2 Posology and method of administration
Treatment with Binocrit has to be initiated under the supervision of physicians experienced in the management of patients with the above indications.


Posology
All other causes of anaemia (iron, folate or vitamin B12 deficiency, aluminium intoxication, infection or inflammation, blood loss, haemolysis and bone marrow fibrosis of any origin) should be evaluated and treated prior to initiating therapy with epoetin alfa, and when deciding to increase the dose. In order to ensure optimum response to epoetin alfa, adequate iron stores should be assured and iron supplementation should be administered if necessary (see section 4.4).

Treatment of symptomatic anemia in adult chronic renal failure patients: Anemia symptoms and sequelae may vary with age, gender, and co-morbid medical conditions; a physician´s evaluation of the individual patient´s clinical course and condition is necessary.

The recommended desired haemoglobin concentration range is between 10 g/dl to 12 g/dl (6.2 to 7.5 mmol/l). Binocrit should be administered in order to increase haemoglobin to not greater than 12 g/dl (7.5 mmol/l). 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.

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 12 g/dl (7.5 mmol/l).


A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be avoided. If the haemoglobin is rising by more than 2 g/dl (1.25 mmol/l) per month, or if the sustained haemoglobin exceeds 12 g/dl (7.5 mmol/l) reduce the Binocrit dose by 25%. If the haemoglobin exceeds 13 g/dl (8.1 mmol/l), discontinue therapy until it falls below 12 g/dl (7.5 mmol/l) and then reinstitute Binocrit therapy at a dose 25% below the previous level.


Patients should be monitored closely to ensure that the lowest approved dose of Binocrit is used to provide adequate control of anemia and of the symptoms of anemia whilst maintaining a haemoglobin concentration below or at 12g/dl (7.5 mmol/l).

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

Treatment with Binocrit is divided into two stages – correction and maintenance phase.

Adult haemodialysis patients:
In patients on haemodialysis where intravenous access is readily available, administration by the intravenous route is preferable.
Correction phase:
The starting dose is 50 IU/kg 3 times per week.
If necessary, increase or decrease the dose by 25 IU/kg (3 times per week) until the desired haemoglobin concentration range between 10 g/dl to 12 g/dl (6.2 to 7.5 mmol/l) is achieved (this should be done in steps of at least four weeks).
Maintenance phase:
The recommended total weekly dose is between 75 IU/kg and 300 IU/kg.
Appropriate adjustment of the dose should be made in order to maintain haemoglobin values within the desired concentration range between 10g/dl to12 g/dl (6.2-7.5 mmol/l).

Patients with very low initial haemoglobin (< 6 g/dl or < 3.75 mmol/l) may require higher maintenance doses than those whose initial anemia is less severe (Hb > 8 g/dl or > 5 mmol/l).


Adult patients with renal insufficiency not yet undergoing dialysis

Where intravenous access is not readily available Binocrit may be administered subcutaneously.

Correction phase
Starting dose of 50 IU/kg, 3 times per week, followed if necessary by a dosage increase with 25 IU/kg increments (3 times per week) until the desired goal is achieved (this should be done in steps of at least four weeks).

Maintenance phase
During the maintenance phase, Binocrit can be administered either 3 times per week, and in the case of subcutaneous administration, once weekly or once every 2 weeks.

Appropriate adjustment of dose and dose intervals should be made in order to maintain haemoglobin values at the desired level: haemoglobin between 10 g/dl and 12 g/dl (6.2 to 7.5 mmol/l). Extending dose intervals may require an increase in dose.

The maximum dosage should not exceed 150 IU/kg, 3 times per week, 240 IU/kg (up to a maximum of 20,000 IU) once weekly, or 480 IU/kg (up to a maximum of 40,000 IU) once every 2 weeks.


Adult peritoneal dialysis patients:
Where intravenous access is not readily available Binocrit may be administered subcutaneously.
Correction phase:
Starting dose of 50 IU/kg 2 times a week.
Maintenance phase:
The recommended maintenance dose is between 25 IU/kg and 50 IU/kg, 2 times per week in 2 equal injections.
Appropriate adjustment of the dose should be made in order to maintain haemoglobin values at the desired level between 10 g/dl to 12 g/dl (6.2 to 7.5 mmol/l).
Treatment of Adult Patients with chemotherapy induced anemia:
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.

Binocrit should be administered to patients with anaemia (e.g. haemoglobin concentration ≤ 10 g/dl (6.2 mmol/l)).
The initial dose is 150 IU/kg subcutaneously, 3 times per week.
Alternatively, Binocrit can be administered at an initial dose of 450 IU/kg subcutaneously once weekly.
Appropriate adjustment of the dose should be made in order to maintain haemoglobin concentrations within the desired concentration range between 10 g/dl to 12 g/dl (6.2 to 7.5 mmol/l).
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 12 g/dl (7.5 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.5 mmol/l) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceed 12 g/dl (7.5 mmol/l) are described below.
• If haemoglobin has increased by at least 1 g/dl (> 0.62 mmol/l) or the reticulocyte count has increased ≥ 40,000 cells/µl above baseline after 4 weeks of treatment, the dose should remain at 150 IU/kg 3 times a week or 450 IU/kg once weekly.
If the haemoglobin increase is < 1 g/dl (< 0.62 mmol/l) and the reticulocyte count has increased < 40,000 cells/µl above baseline, increase the dose to 300 IU/kg 3 times per week. If after an additional 4 weeks of therapy at 300 IU/kg 3 times per week, the haemoglobin has increased ≥ 1 g/dl (≥ 0.62 mmol/l) or the reticulocyte count has increased ≥ 40,000 cells/µl the dose should remain at 300 IU/kg 3 times per week.
• if the haemoglobin has increased < 1 g/dl (< 0.62 mmol/l) and the reticulocyte count has increased < 40,000 cells/µl above baseline, response is unlikely and treatment should be discontinued.


Dosage adjustment to maintain haemoglobin concentration between 10 g/dl-12 g/dl (6.2-7.5 mmol/l):
If the haemoglobin concentration level is increasing by more than 2 g/dl (1.25 mmol/l) per month, or if the haemoglobin exceeds 12 g/dl (7.5 mmol/l), reduce the Binocrit dose by about 25 to 50%.
If the haemoglobin exceeds 13 g/dl (8.1 mmol/l), discontinue therapy until it falls below 12 g/dl (7.5 mmol/l) and then reinstitute Binocrit therapy at a dose 25% below the previous dose.

The recommended dosing regimen is described in the following diagram: 


Patients should be monitored closely to ensure that the lowest approved dose of erythropoiesis stimulating agent (ESA) is used to provide adequate control of the symptoms of anaemia.
Epoetin alfa therapy should continue until one month after the end of chemotherapy.


Treatment of adult surgery patients in an autologous predonation programme: Mildly anaemic patients (haematocrit of 33-39%) requiring predeposit of ≥4 units of blood should be treated with Binocrit at a dose of 600 IU/kg intravenously, 2 times weekly for 3 weeks prior to surgery. Binocrit should be administered after the completion of the blood donation procedure.



Treatment of adult patients scheduled for major elective orthopaedic surgery: 
The recommended dose is Binocrit 600 IU/kg, administered subcoutanously weekly for three weeks (days 21, 14 and 7) prior to surgery and on the day of surgery (day 0).
In cases where there is a medical need to shorten the lead time before surgery to less than three weeks, Binocrit 300 IU/kg epoetin alfa should be administered subcoutanously daily for 10 consecutive days prior to surgery, on the day of surgery and for four days immediately thereafter.
If the haemoglobin level reaches 15 g/dl (9.38 mmol/l), or higher, during the perioprative period, administration of Binocrit should be stopped and further dosages should not be administered.


Paediatric population:
Treatment of symptomatic anemia in chronic renal failure patients on haemodialysis Anemia symptoms and sequelae may vary with age, gender, and co-morbid medical conditions; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.
In paediatric patients the recommended haemoglobin concentration range is between 9.5 g/dl to 11 g/dl (5.9 to 6.8 mmol/l). Binocrit should be administered in order to increase haemoglobin to not greater than 11 g/dl (6.8 mmol/l). 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.
Patients should be monitored closely to ensure that the lowest approved dose of Binocrit is used to provide adequate control of anaemia and of the symptoms of anemia.
Treatment with Binocrit is divided into two stages – correction and maintenance phase.
In paediatric patients on haemodialysis where intravenous access is readily available, administration by the intravenous route is preferable.


Correction phase:
The starting dose is 50 IU/kg intravenously 3 times per week.

If necessary, increase or decrease the dose by 25 IU/kg (3 times per week) until the desired haemoglobin concentration range of between 9.5 g/dl to 11 g/dl (5.9 to 6.8 mmol/l) is achieved (this should be done in steps of at least four weeks).

Maintenance phase:
Appropriate adjustment of the dose should be made in order to maintain haemoglobin levels within the desired concentration range between 9.5 g/dl to 11 g/dl (5.9 to 6.8 mmol/l).
Generally, children under 30 kg require higher maintenance doses than children over 30 kg and adults.
Paediatric patients with very low initial haemoglobin (< 6.8 g/dl or < 4.25 mmol/l) may require higher maintenance doses than patients whose initial haemoglobin is higher (> 6.8 g/dl or > 4.25 mmol/l).

Anaemia in chronic renal failure patients before initiation of dialysis or on peritoneal dialysis The safety and efficacy of epoetin alfa in chronic renal failure patients with anemia before initiation of dialysis or on peritoneal dialysis have not been established. Currently available data for subcutaneous use of epoetin alfa in these populations are described in section 5.1 but no recommendation on posology can be made.

Treatment of paediatric patients with chemotherapy-induced anaemia
The safety and efficacy of epoetin alfa in paediatric patients receiving chemotherapy have not been established (see section 5.1).

Treatment of paediatric surgery patients in an autologous predonation programme The safety and efficacy of epoetin alfa in paediatrics have not been established. No data are available.

Treatment of paediatric patients scheduled for major elective orthopaedic surgery The safety and efficacy of epoetin alfa in paediatrics have not been established. No data are available.


Method of administration
Precautions to be taken before handling or administering the medicinal product.
Before use, leave the Binocrit syringe to stand until it reaches room temperature. This usually takes between 15 and 30 minutes.
As with any other injectable product, check that there are no particles in the solution or change in colour. Binocrit is a sterile but unpreserved product and is for single use only. Administer the amount required.

Treatment of symptomatic anaemia in adult chronic renal failure patients In patients with chronic renal failure where intravenous access is routinely available (haemodialysis patients) administration of Binocrit by the intravenous route is preferable.

Where intravenous access is not readily available (patients not yet undergoing dialysis and peritoneal dialysis patients) Binocrit may be administered as a subcutaneous injection.

Treatment of adult patients with chemotherapy-induced anaemia
Binocrit should be administered as a subcutaneous injection.

Treatment of adult surgery patients in an autologous predonation programme Binocrit should be administered by the intravenous route.

Treatment of adult patients scheduled for major elective orthopaedic surgery Binocrit should be administered as a subcutaneous injection.

Treatment of symptomatic anaemia in paediatric chronic renal failure patients on haemodialysis
In paediatric patients with chronic renal failure where intravenous access is routinely available (haemodialysis patients) administration of Binocrit by the intravenous route is preferable.


Intravenous administration:
Administer over at least one to five minutes, depending on the total dose. In haemodialysed patients, a bolus injection may be given during the dialysis session through a suitable venous port in the dialysis line. Alternatively, the injection can be given at the end of the dialysis session via the fistula needle tubing, followed by 10 ml of isotonic saline to rinse the tubing and ensure satisfactory injection of the product into the circulation. (see Posology, “Adult haemodialysis patients”).
A slower injection is preferable in patients who react to the treatment with “flu-like” symptoms.
(see section 4.8).
Do not administer Binocrit by intravenous infusion or in conjunction with other medicinal product solutions (please refer to section 6.6 for further information).

Subcutaneous administration:
A maximum volume of 1 ml at one injection site should generally not be exceeded. In case of larger volumes, more than one site should be chosen for the injection. The injections are given in the limbs or the anterior abdominal wall.
In those situations in which the physician determines that a patient or caregiver can safely and effectively administer Binocrit subcutaneously, instruction as to the proper dosage and administration should be provided.


Graduation rings
The syringe contains graduation rings to provide for the administration of a part of the dose (see section 6.6). However the product is for single use only. Only one dose of Binocrit from each syringe should be taken.

“Instructions on how to inject Binocrit yourself” can be found at the end of the package leaflet.