Posology : מינונים

4.2 Posology and Method of Administration

ARANESP® treatment should be initiated by physicians experienced in the above mentioned indications.

ARANESP® may be administered subcutaneously by the patient or a carer after being trained by a doctor, nurse or pharmacist.

ARANESP® is supplied ready for use in a pre-filled syringe or pre-filled pen (Sure-Click®).

The pre-filled syringe is administered either subcutaneously or intravenously.
The pre-filled pen is only for subcutaneous administration.

The instructions for use, handling and disposal are given in section special precautions for disposal.

Treatment of Symptomatic Anemia in Chronic Renal Failure Patients
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.
ARANESP® should be administered either subcutaneously or intravenously in order to increase 
hemoglobin to not greater than 12 g/dL (7.5 mmol/L). Subcutaneous use is preferable in patients who are not receiving hemodialysis to avoid the puncture of peripheral veins.

Patients should be monitored closely to ensure that the lowest approved effective dose of ARANESP® is used to provide adequate control of the symptoms of anemia whilst maintaining a hemoglobin concentration below or at 12 g/dL (7.5 mmol/L). Caution should be exercised with escalation of ARANESP® doses in patients with chronic renal failure. In patients with a poor hemoglobin response to ARANESP®, alternative explanations for the poor response should be considered (see sections 4.4 and 5.1).

Due to intra-patient variability, occasional individual hemoglobin values for a patient above and below the desired hemoglobin level may be observed. Hemoglobin variability should be addressed through dose management, with consideration for the hemoglobin target range of 10 g/dL (6.2 mmol/L) to 12 g/dL (7.5 mmol/L). A sustained hemoglobin level of greater than 12 g/dL (7.5 mmol/L) should be avoided; guidance for appropriate dose adjustment for when hemoglobin values exceeding 12 g/dL (7.5 mmol/L) are observed are described below.

A rise in hemoglobin 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.

Treatment with ARANESP® is divided into two stages – correction and maintenance phase.
Adult patients with chronic renal failure

Correction phase:

The initial ARANESP® dosage by subcutaneous or intravenous administration is 0.45 mcg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis the following initial doses can also be administered subcutaneously as a single injection: 0.75 mcg/kg once every two weeks or 1.5 mcg/kg once monthly. If the increase in hemoglobin is inadequate (less than 1 g/dL (0.6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks.

If the rise in hemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the ARANESP® dose by approximately 25%. If the hemoglobin exceeds 12 g/dL (7.5 mmol/L), a dose reduction should be considered. If the hemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, hemoglobin continues to increase, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

The hemoglobin should be measured every one or two weeks until it is stable. Thereafter the hemoglobin can be measured at longer intervals.

Maintenance phase:

In dialysis patients, ARANESP® may continue to be administered as a single injection once weekly or once every two weeks. Dialysis patients converting from once weekly to once every other week dosing with ARANESP® should initially receive a dose equivalent to twice the previous once weekly dose.

In patients not on dialysis, ARANESP® may continue to be administered as a single injection once weekly or once every two weeks or once monthly. For patients treated with ARANESP® once every two weeks, after the target hemoglobin has been achieved, ARANESP® may then be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two-week dose.

Dosing should be titrated as necessary to maintain the hemoglobin target.

If a dose adjustment is required to maintain hemoglobin at the desired level, it is recommended that the dose of ARANESP® is adjusted by approximately 25%.

If the rise in hemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the hemoglobin exceeds 12 g/dL (7.5 mmol/L), a dose reduction should be considered. If the hemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, hemoglobin continues to increase, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

After any dose or schedule adjustment the hemoglobin should be monitored every one or two weeks.
Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks.

When changing the route of administration the same dose must be used and the hemoglobin monitored every one or two weeks so that the appropriate ARANESP® dose adjustments can be made to keep the hemoglobin at the desired level.

Clinical studies have demonstrated that adult patients receiving r-HuEPO one, two or three times weekly may be converted to once weekly or once every other week ARANESP® The initial weekly dose of ARANESP® (mcg/week) can be determined by dividing the total weekly dose of r-HuEPO (IU/week) by 200. The initial every other week dose of ARANESP® (mcg/every other week) can be determined by dividing the total cumulative dose of r-HuEPO administered over a two-week period by 200. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients. When substituting ARANESP® for r-HuEPO the hemoglobin should be monitored every one or two weeks and the same route of administration should be used.

Pediatric population with chronic renal failure (≥ 1 year of age)

Treatment of pediatric patients younger than 1 year of age has not been studied in randomized clinical trials (see section 5.1).

Correction phase:

For patients ≥ 1 year of age, the initial dose by subcutaneous or intravenous administration is 0.45 mcg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, an initial dose of 0.75 mcg/kg may be administered subcutaneously as a single injection once every two weeks. If the increase in hemoglobin is inadequate (less than 1 g/dL (0.6 mmol/L) in four weeks) increase the dose by approximately 25%. Dose increases must not be made more frequently than once every four weeks.

If the rise in hemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the hemoglobin exceeds 12 g/dL (7.5 mmol/L), a dose reduction should be considered. If the hemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, hemoglobin continues to increase, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

The hemoglobin should be measured every one or two weeks until it is stable. Thereafter the hemoglobin can be measured at longer intervals.

Correction of anemia in pediatric patients with once monthly ARANESP® dosing frequency has not been studied.

Maintenance phase:

For pediatric patients ≥ 1 year of age, in the maintenance phase, ARANESP® may continue to be administered as a single injection once weekly or once every two weeks. Patients < 6 years of age may need higher doses for maintenance of hemoglobin than patients above that age. Dialysis patients converting from once weekly to once every other week dosing with ARANESP® should initially receive a dose equivalent to twice the previous once weekly dose.

Clinical data in pediatric patients has demonstrated that patients receiving r-HuEPO two or three times weekly may be converted to once weekly ARANESP®, and those receiving r-HuEPO once weekly may be converted to once every other week ARANESP®. The initial weekly pediatric dose of ARANESP® (mcg/week) can be determined by dividing the total weekly dose of r-HuEPO (IU/week) by 240. The initial every other week dose of ARANESP® (mcg/every other week) can be determined by dividing the total cumulative dose of r-HuEPO administered over a two-week period by 240. Because of individual variability, titration to optimal therapeutic doses is expected for individual patients. When substituting ARANESP® for r-HuEPO the hemoglobin should be monitored every one or two weeks and the same route of administration should be used.

Dosing should be titrated as necessary to maintain the hemoglobin target.

If a dose adjustment is required to maintain hemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%.

If the rise in hemoglobin is greater than 2 g/dL (1.25 mmol/L) in four weeks reduce the dose by approximately 25%, depending on the rate of increase. If the hemoglobin exceeds 12 g/dL (7.5 mmol/L), a dose reduction should be considered. If the hemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, hemoglobin continues to increase, the dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.

Patients starting dialysis during treatment with ARANESP® should be closely monitored for adequate control of their hemoglobin.

After any dose or schedule adjustment the hemoglobin should be monitored every one or two weeks.
Dose changes in the maintenance phase of treatment should not be made more frequently than every two weeks.

When changing the route of administration the same dose must be used and the hemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the hemoglobin at the desired level.

Treatment of Symptomatic Chemotherapy-Induced Anemia in Cancer Patients 
ARANESP® should be administered by the subcutaneous route to patients with anemia (e.g., hemoglobin concentration ≤ 10 g/dL (6.2 mmol/L)) in order to increase hemoglobin to not greater than 12 g/dL (7.5 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.

Due to intra-patient variability, occasional individual hemoglobin values for a patient above and below the desired hemoglobin level may be observed. Hemoglobin variability should be addressed through dose management, with consideration for the hemoglobin target range of 10 g/dL (6.2 mmol/L) to 12 g/dL (7.5 mmol/L). A sustained hemoglobin level of greater than 12 g/dL (7.5 mmol/L) should be avoided; guidance for appropriate dose adjustments for when hemoglobin values exceeding 12 g/dL (7.5 mmol/L) are observed are described below.

The recommended initial dose is 500 mcg (6.75 mcg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 mcg/kg body weight. If the clinical response of the patient (fatigue, hemoglobin response) is inadequate after nine weeks, further therapy may not be effective.

ARANESP® therapy should be discontinued approximately four weeks after the end of chemotherapy.

Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50% in order to ensure that the lowest approved dose of ARANESP® is used to maintain hemoglobin at a level that controls the symptoms of anemia. Appropriate dose titration between 500 mcg, 300 mcg, and 150 mcg should be considered.

Patients should be monitored closely, if the hemoglobin exceeds 12 g/dL (7.5 mmol/L), the dose should be reduced by approximately 25 to 50%. Treatment with ARANESP® should be temporarily discontinued if hemoglobin levels exceed 13 g/dL (8.1 mmol/L). Therapy should be reinitiated at approximately 25% lower than the previous dose after hemoglobin levels fall to 12 g/dL (7.5 mmol/L) or below.

If the rise in hemoglobin is greater than 2 g/dL (1.25 mmol/L) in 4 weeks, the dose should be reduced by 25 to 50%.