Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Amgen Europe B.V., Minervum 7061, 4817 ZK Breda, The Netherlands
Treatment of symptomatic anaemia associated with chronic renal failure (CRF) in adults and paediatric patients (see section 4.2).
Treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies receiving chemotherapy.
Aranesp treatment should be initiated by physicians experienced in the above mentioned indications.
Anaemia 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 haemoglobin to not greater than 12 g/dL (7.5 mmol/L). Subcutaneous use is preferable in patients who are not receiving haemodialysis 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 anaemia whilst maintaining a haemoglobin 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 haemoglobin 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 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 exceeding 12 g/dl (7.5 mmol/l) 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.
Treatment with Aranesp is divided into two stages, correction and maintenance phase. Guidance is given separately for adult and paediatric patients.
The initial dose by subcutaneous or intravenous administration is 0.45 µg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, an initial dose of 0.75 μg/kg may be administered subcutaneously as a single injection once every two weeks. If the increase in haemoglobin 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 haemoglobin is greater than 2 g/dl (1.25 mmol/l) in four weeks reduce the dose by approximately 25%. If the haemoglobin exceeds 12 g/dl (7.5 mmol/l), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.
In the maintenance phase, 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 haemoglobin 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 haemoglobin target.
If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%.
If the rise in haemoglobin 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 haemoglobin exceeds 12 g/dl (7.5 mmol/l), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin 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 haemoglobin 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 haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin 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 (µg/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 (μg/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 haemoglobin should be monitored every one or two weeks and the same route of administration should be used.
Treatment of paediatric patients younger than 1 year of age has not been studied.
For patients ≥11 years of age, the initial dose by subcutaneous or intravenous administration is 0.45 µg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, an initial dose of 0.75 μg/kg may be administered subcutaneously as a single injection once every two weeks. If the increase in haemoglobin 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 haemoglobin 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 haemoglobin exceeds 12 g/dl (7.5 mmol/l), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
The haemoglobin should be measured every one or two weeks until it is stable. Thereafter the haemoglobin can be measured at longer intervals.
Correction of anaemia in paediatric patients with once monthly Aranesp dosing frequency has not been studied.
For paediatric patients ≥11 years of age, in the maintenance phase, 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 ≥11 years of age not on dialysis, once the target haemoglobin has been achieved with once every two week dosing, Aranesp may be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.
Clinical data in paediatric 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 paediatric dose of Aranesp (µg/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 (μg/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 haemoglobin 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 haemoglobin target.
If a dose adjustment is required to maintain haemoglobin at the desired level, it is recommended that the dose is adjusted by approximately 25%.
If the rise in haemoglobin 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 haemoglobin exceeds 12 g/dl (7.5 mmol/l), a dose reduction should be considered. If the haemoglobin continues to increase, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin 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 haemoglobin.
After any dose or schedule adjustment the haemoglobin 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 haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the haemoglobin at the desired level.
Aranesp should be administered by the subcutaneous route to patients with anaemia (e.g. haemoglobin concentration ≤10 g/dl (6.2 mmol/l)) in order to increase haemoglobin to not greater than 12 g/dl (7.5 mmol/l). Anaemia 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 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 adjustments for when haemoglobin values exceeding 12 g/dl (7.5 mmol/l) are observed are described below.
The recommended initial dose is 500 μg (6.75 μg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 μg/kg body weight. If the clinical response of the patient (fatigue, haemoglobin 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 haemoglobin at a level that controls the symptoms of anaemia. Appropriate dose titration between 500 μg, 300 μg, and 150 μg should be considered.
Patients should be monitored closely, if the haemoglobin 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 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 12 g/dl (7.5 mmol/l) or below.
If the rise in haemoglobin is greater than 2 g/dl (1.25 mmol/l) in 4 weeks, the dose should be reduced by 25 to 50%.
Aranesp may be administered subcutaneously by the patient or a carer after being trained by a doctor, nurse or pharmacist.
Aranesp is administered either subcutaneously or intravenously as described in the posology. Rotate the injection sites and inject slowly to avoid discomfort at the site of injection. Aranesp is supplied ready for use in a pre-filled syringe.
Aranesp in a pre-filled pen is only for subcutaneous administration. Rotate the injection sites to avoid discomfort at the site of injection. Aranesp is supplied ready for use in a pre-filled pen.
Aranesp is administered either subcutaneously or intravenously as described in the posology. Rotate the injection sites and inject slowly to avoid discomfort at the site of injection. Aranesp is supplied ready for use in a vial.
The instructions for use, handling and disposal are given in section 6.6.
The maximum amount of Aranesp that can be safely administered in single or multiple doses has not been determined. Therapy with Aranesp can result in polycythaemia if the haemoglobin is not carefully monitored and the dose appropriately adjusted. Cases of severe hypertension have been observed following overdose with Aranesp (see section 4.4).
In the event of polycythaemia, Aranesp should be temporarily withheld (see section 4.2). If clinically indicated, phlebotomy may be performed.
3 years.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
For the purpose of ambulatory use, Aranesp may be removed from storage once for a maximum single period of seven days at room temperature (up to 25°C). Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25°C) it must either be used within 7 days or disposed of.
Aranesp 10 micrograms solution for injection in pre-filled syringe: 0.4 mL solution for injection (25 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 15 micrograms solution for injection in pre-filled syringe: 0.375 mL solution for injection (40 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 20 micrograms solution for injection in pre-filled syringe: 0.5 mL solution for injection (40 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 30 micrograms solution for injection in pre-filled syringe: 0.3 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 40 micrograms solution for injection in pre-filled syringe: 0.4 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 50 micrograms solution for injection in pre-filled syringe: 0.5 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 60 micrograms solution for injection in pre-filled syringe: 0.3 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 80 micrograms solution for injection in pre-filled syringe: 0.4 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 100 micrograms solution for injection in pre-filled syringe: 0.5 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 130 micrograms solution for injection in pre-filled syringe: 0.65 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 150 micrograms solution for injection in pre-filled syringe: 0.3 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 300 micrograms solution for injection in pre-filled syringe: 0.6 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 500 micrograms solution for injection in pre-filled syringe: 1 mL solution for injection (500 mcg/mL darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
The syringes may be presented in either blistered (1- and 4-pack), with or without an automatic needle guard or non-blistered packaging (1-pack only).
The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex). See section 4.4.
Aranesp 10 micrograms solution for injection in pre-filled pen: 0.4 mL solution for injection (25 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 15 micrograms solution for injection in pre-filled pen: 0.375 mL solution for injection (40 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 20 micrograms solution for injection in pre-filled pen: 0.5 mL solution for injection (40 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 30 micrograms solution for injection in pre-filled pen: 0.3 mL solution for injection (100 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 40 micrograms solution for injection in pre-filled pen: 0.4 mL solution for injection (100 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 50 micrograms solution for injection in pre-filled pen: 0.5 mL solution for injection (100 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 60 micrograms solution for injection in pre-filled pen: 0.3 mL solution for injection (200 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 80 micrograms solution for injection in pre-filled pen: 0.4 mL solution for injection (200 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 100 micrograms solution for injection in pre-filled pen: 0.5 mL solution for injection (200 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 130 micrograms solution for injection in pre-filled pen: 0.65 mL solution for injection (200 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 150 micrograms solution for injection in pre-filled pen: 0.3 mL solution for injection (500 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 300 micrograms solution for injection in pre-filled pen: 0.6 mL solution for injection (500 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
Aranesp 500 micrograms solution for injection in pre-filled pen: 1 mL solution for injection (500 mcg/mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled pens.
The needle cap of the pre-filled pen contains dry natural rubber (a derivative of latex). See section 4.4.
Aranesp 25 micrograms solution for injection in vial: 1 mL solution for injection (25 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Aranesp 40 micrograms solution for injection in vial: 1 mL solution for injection (40 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Aranesp 60 micrograms solution for injection in vial: 1 mL solution for injection (60 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Aranesp 100 micrograms solution for injection in vial: 1 mL solution for injection (100 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Aranesp 200 micrograms solution for injection in vial: 1 mL solution for injection (200 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Aranesp 300 micrograms solution for injection in vial: 1 mL solution for injection (300 mcg/mL darbepoetin alfa) in a type 1 glass vial with fluoropolymer laminated elastomeric stopper and an aluminium seal with flip-off dust cover. Pack size of 1 or 4 vials.
Not all pack sizes may be marketed.
The carton contains a package leaflet with the full instructions for use and handling.
The Aranesp (SureClick) pre-filled pen delivers the complete dose of each presentation.
Aranesp is a sterile but unpreserved product. Do not administer more than one dose. Any medicinal product remaining should be disposed of.
Before administration the Aranesp solution should be inspected for visible particles. Only solutions which are colourless, clear or slightly opalescent, should be injected. Do not shake. Allow the container to reach room temperature before injecting.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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