References
1. Locatelli F, on behalf of the NESP 990748 Study Group. ARANESP® (darbepoetin alfa) unit dosing is effective in the treatment of renal
anaemia in patients with end-stage renal disease. Poster presented at: XXXIX ERA-EDTA Congress; July 14-17, 2002; Copenhagen, Denmark.
2. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant.
2001;16(suppl 3):3-13.
®
Aranesp (darbepoetin alfa)
Brief Prescribing Information
to pregnant women. Do not administer to women who are breast-
feeding. When Aranesp® therapy is absolutely indicated,
breast-feeding must be discontinued.
Undesirable Effects: Undesirable effects considered related to
treatment with Aranesp® from controlled clinical studies with an
incidence of >1% to ≤10% are headache, hypertension, thrombosis
of the vascular access, and injection site pain. Injection site pain was
seen more frequently than with r-HuEPO, but was generally mild and
transient and occurred predominantly after the first subcutaneous
injection.
Overdose: Wide therapeutic margin. In the event of polycythaemia,
Aranesp® should be temporarily withheld. If clinically indicated,
phlebotomy may be performed.
Pharmaceutical Precautions: Aranesp® should not be mixed or
administered as an infusion with other medicinal products. Store at
2°C to 8°C (in a refrigerator). Do not freeze. Keep container in outer
carton to protect from light. For ambulatory use, Aranesp® may be
removed from storage once for a maximum single period of 7 days
at room temperature (up to 25°C).
Please refer to the Summary of Product Characteristics before
prescribing Aranesp®
Pharmaceutical Form: Solution for injection presented in prefilled
syringes containing 10, 15, 20, 30, 40, 50, 60, 80, 100, 150 and 300
micrograms darbepoetin alfa or in vials containing 15, 25, 40 and
60 micrograms per mL darbepoetin alfa, for single-dose use only.
Indication: Treatment of anaemia associated with chronic renal
failure in adults and paediatric subjects ≥11 years of age.
Dosage and Administration: Aranesp® can be administered either
subcutaneously or intravenously as a single injection once weekly
or once every two weeks. The aim of treatment is to increase
haemoglobin to greater than 11 g/dL (6.8 mmol/L); the exact target
haemoglobin concentration above this needs to be established for
individual patients. A rise in haemoglobin of greater than 2.0 g/dL
(1.25 mmol/L) over a four week period or a haemoglobin level greater
than 14 g/dL (8.7 mmol/L) should be avoided.
Correction Phase: Initial dose by SC or IV administration is 0.45 µg/kg
body weight as a single injection once weekly. 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 2.5 g/dL (1.6 mmol/L) in
four weeks, reduce the dose by between 25% and 50%, depending
on the rate of increase. If the haemoglobin exceeds 14 g/dL
(8.7 mmol/L), discontinue therapy until it falls below 13 g/dL
(8.1 mmol/L) and then restart the treatment at approximately
25% below the previous dose. Measure haemoglobin every
one or two weeks until stable; periodically thereafter.
Maintenance Phase: If a dose adjustment is required to maintain
haemoglobin at the desired level, adjust dose by approximately 25%.
If haemoglobin exceeds 14 g/dL (8.7 mmol/L), discontinue therapy
until it falls below 13 g/dL (8.1 mmol/L) and then restart at
approximately 25% below the previous dose. After any dose
adjustment, monitor haemoglobin every one or two weeks. Dose
changes in the maintenance phase should not be made more
frequently than every two weeks. When changing route of
administration, the same dose must be used and haemoglobin
monitored every one or two weeks. No difference has been observed
between the average weekly dose administered by IV or SC injection.
Patients receiving r-HuEPO two or three times weekly may change to
once-weekly Aranesp®; those receiving once-weekly r-HuEPO may
change to Aranesp® once every other week. Determine initial dose
of Aranesp® (µg/week) by dividing total weekly dose of r-HuEPO
(IU/week) by 200. Titrate to optimal therapeutic dose. The same route
of administration should be used and haemoglobin should be
monitored every one or two weeks.
Legal Category: Medicinal product subject to restricted medical
prescription.
Presentation and Marketing Authorisation Numbers:
Aranesp® 10 µg: 1 prefilled syringe: EU/1/01/185/001;
Aranesp® 10 µg: 4 prefilled syringes: EU/1/01/185/002;
Aranesp® 15 µg: 1 prefilled syringe: EU/1/01/185/003;
Aranesp® 15 µg: 4 prefilled syringes: EU/1/01/185/004;
Aranesp® 20 µg: 1 prefilled syringe: EU/1/01/185/005;
Aranesp® 20 µg: 4 prefilled syringes: EU/1/01/185/006;
Aranesp® 30 µg: 1 prefilled syringe: EU/1/01/185/007;
Aranesp® 30 µg: 4 prefilled syringes: EU/1/01/185/008;
Aranesp® 40 µg: 1 prefilled syringe: EU/1/01/185/009;
Aranesp® 40 µg: 4 prefilled syringes: EU/1/01/185/010;
Aranesp® 50 µg: 1 prefilled syringe: EU/1/01/185/011;
Aranesp® 50 µg: 4 prefilled syringes: EU/1/01/185/012;
Aranesp® 60 µg: 1 prefilled syringe: EU/1/01/185/013;
Aranesp® 60 µg: 4 prefilled syringes: EU/1/01/185/014;
Aranesp® 80 µg: 1 prefilled syringe: EU/1/01/185/015;
Aranesp® 80 µg: 4 prefilled syringes: EU/1/01/185/016;
Aranesp® 100 µg: 1 prefilled syringe: EU/1/01/185/017;
Aranesp® 100 µg: 4 prefilled syringes: EU/1/01/185/018;
Aranesp® 150 µg: 1 prefilled syringe: EU/1/01/185/019;
Aranesp® 150 µg: 4 prefilled syringes: EU/1/01/185/020;
Aranesp® 300 µg: 1 prefilled syringe: EU/1/01/185/021;
Aranesp® 300 µg: 4 prefilled syringes: EU/1/01/185/022;
Aranesp® 15 µg/mL: 1 vial: EU/1/01/185/023;
Contraindications: Hypersensitivity to darbepoetin alfa, r-HuEPO
or excipients. Poorly controlled hypertension.
Aranesp® 15 µg/mL: 4 vials: EU/1/01/185/024;
Special Warnings and Precautions: Evaluate iron status prior to
and during treatment; supplementary iron therapy is recommended
where serum ferritin values are below 100 mg/L or transferrin
saturation is below 20%. Nonresponse to therapy should be
investigated. Monitor blood pressure in all chronic renal failure
patients, particularly when initiating Aranesp® therapy. In patients
with chronic renal failure and clinical evidence of ischaemic heart
disease or congestive heart failure, determine target haemoglobin
individually – an upper limit of 12 g/dL should be aimed for, unless
severe symptoms dictate otherwise. Aranesp® should be used with
caution in patients with liver disease. Serum potassium levels should
be monitored regularly during Aranesp® therapy; if an elevated or
rising potassium level is observed, consider ceasing Aranesp®
administration until potassium level is corrected. Aranesp® should be
used with caution in patients with sickle cell anaemia or epilepsy.
Misuse of Aranesp® by healthy persons may lead to an excessive
increase in packed cell volume, which may be associated with
life-threatening cardiovascular complications.
Aranesp® 25 µg/mL: 1 vial: EU/1/01/185/025;
Aranesp® 25 µg/mL: 4 vials: EU/1/01/185/026;
Aranesp® 40 µg/mL: 1 vial: EU/1/01/185/027;
Aranesp® 40 µg/mL: 4 vials: EU/1/01/185/028;
Aranesp® 60 µg/mL: 1 vial: EU/1/01/185/029;
Aranesp® 60 µg/mL: 4 vials: EU/1/01/185/030.
Availability of presentations will vary in national regions.
Marketing Authorisation Holder: Amgen Europe B.V., Minervum
7061, NL-4817 ZK Breda, The Netherlands. Further information is
available from Amgen (Europe) AG, Alpenquai 30, P.O. Box 2065,
Lucerne, Switzerland CH-6002. Additional information may be
obtained from your local Amgen office.
Date of preparation: June 2002.
Interactions: If darbepoetin alfa is given concomitantly with
cyclosporin, monitor blood levels of cyclosporin and adjust the
cyclosporin dose as the haemoglobin rises.
Amgen (Europe) AG
Lucerne, Switzerland
Pregnancy and Lactation: No adequate experience in human
© 2003 Amgen Inc. All rights reserved.
pregnancy and lactation. Exercise caution when prescribing Aranesp®
For European nephrology patients 200 IU r-HuEPO = 1 µg Aranesp® is an appropriate
dose conversion factor to use when switching patients from r-HuEPO to Aranesp®.