Aranesp

Package leaflet: Information for the user

Aranesp 10 micrograms injectable solution in pre-filled syringe, 15 micrograms injectable solution in pre-filled syringe, 20 micrograms injectable solution in pre-filled syringe, 30 micrograms injectable solution in pre-filled syringe, 40 micrograms injectable solution in pre-filled syringe, 50 micrograms injectable solution in pre-filled syringe, 60 micrograms injectable solution in pre-filled syringe, 80 micrograms injectable solution in pre-filled syringe, 100 micrograms injectable solution in pre-filled syringe, 130 micrograms injectable solution in pre-filled syringe, 150 micrograms injectable solution in pre-filled syringe, 300 micrograms injectable solution in pre-filled syringe, 500 micrograms injectable solution in pre-filled syringe

darbepoetin alfa
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse (see section 4).

Contents of this leaflet

1. What Aranesp is and what it is used for
2. What you need to know before you use Aranesp
3. How to use Aranesp
4. Possible side effects
5. How to store Aranesp
6. Contents of the pack and other information
7. Instructions for injecting Aranesp from a pre-filled syringe

1. What Aranesp is and what it is used for

Your doctor has prescribed Aranesp (an anti-anaemic agent) to treat your anaemia. You have anaemia when there are not enough red blood cells in your blood, and symptoms of anaemia may include fatigue, weakness, and shortness of breath.
Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is produced by the kidneys and stimulates the bone marrow to produce more red blood cells. The active substance in Aranesp is darbepoetin alfa, which is produced by genetic engineering techniques in Chinese hamster ovary cells (CHO-K1).

If you have chronic renal failure
Aranesp is used to treat symptomatic anaemia associated with chronic renal failure in adults and children. In renal failure, the kidneys do not produce enough of the natural hormone erythropoietin, which can often lead to anaemia.
It will take some time for your body to produce more red blood cells, so it will take approximately four weeks before you notice any effect. The effectiveness of Aranesp in treating anaemia is not affected by routine dialysis procedures.

If you are receiving chemotherapy
Aranesp is used to treat symptomatic anaemia in adult patients with non-myeloid tumours (non-myeloid neoplasms) who are receiving chemotherapy.
One of the main side effects of chemotherapy is that it prevents the bone marrow from producing enough blood cells. Towards the end of chemotherapy treatment, especially if you have received intensive chemotherapy, the number of red blood cells may decrease, causing anaemia.

2. What you need to know before using Aranesp

Do not use Aranesp

• if you are allergic to darbepoetin alfa or to any of the other ingredients of this medicine listed in section 6;
• if you have been diagnosed with high blood pressure that is not currently controlled with other medicines prescribed by your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Aranesp.
Inform your doctor if you have or have had:

• high blood pressure currently controlled with medicines prescribed by your doctor;
• sickle cell anemia;
• epileptic seizures (convulsions);
• convulsions (seizures or fits);
• liver diseases;
• a significant lack of response to medicines used to treat anemia;
• allergy to latex (the needle cap of the pre-filled syringe contains a latex derivative);
• hepatitis C.

Special warnings:

• If you experience symptoms such as unusual tiredness and loss of strength, you may have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that your body stops or reduces the production of red blood cells, leading to severe anemia. If you experience these symptoms, inform your doctor, who will decide on the best treatment strategy for your anemia.
• Be especially careful if you are taking other medicines that stimulate red blood cell production: Aranesp belongs to a group of products that stimulate red blood cell production, similar to human erythropoietin. Healthcare professionals must always record the correct name of the medicine you are taking.
• If you have chronic kidney failure and, in particular, do not respond adequately to Aranesp, your doctor will check your Aranesp dose because repeated dose increases of Aranesp in case of non-response to treatment may increase the risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• Your doctor should aim to keep your hemoglobin level between 10 and 12 g/dL. Your doctor will ensure that your hemoglobin level does not exceed a specific threshold, as high hemoglobin levels may put you at risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• If you have symptoms including severe headache, drowsiness, confusion, vision problems, nausea, vomiting, or convulsions, this may indicate very high blood pressure. If you experience these symptoms, contact your doctor immediately.
• If you have a tumor, you should know that Aranesp can act as a growth factor for blood cells and, in some circumstances, may have negative effects on the tumor. Depending on your specific situation, a blood transfusion may be preferable. Discuss this with your doctor.
• Improper use by healthy individuals may cause heart and vascular problems that pose an immediate life-threatening risk.
• Severe skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with epoetin treatment. SJS/TEN may initially appear as red spots or circular patches, often with central blisters, on the trunk. Mouth, throat, nose, genital, and eye ulcers (swollen and red eyes) may also occur. These severe skin reactions are often preceded by fever and/or flu-like symptoms. Skin rashes may progress to widespread skin peeling and life-threatening complications. If you develop a severe skin rash or any of these skin symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention.

Other medicines and Aranesp
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Medicines such as cyclosporine and tacrolimus (medicines that suppress the immune system) may be affected by changes in the number of red blood cells in the blood. It is important that you inform your doctor if you are taking any of these medicines.

Aranesp with food and drink
Food and drink do not affect Aranesp.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Aranesp has not been studied in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you think you might be pregnant; or
• you are planning a pregnancy.

It is not known whether darbepoetin alfa is excreted in breast milk. If you use Aranesp, you must stop breastfeeding.

Driving and using machines
Aranesp should not affect your ability to drive or operate machinery.

Aranesp contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.

3. How to use Aranesp

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Based on certain blood tests, your doctor has determined that you need Aranesp because your haemoglobin level is 10 g/dL or lower. Your doctor will inform you of the amount and frequency of Aranesp administration required to maintain a haemoglobin level between 10 and 12 g/dL.
This may vary depending on whether you are an adult or a child.

How to self-administer Aranesp injections
Your doctor may decide that it is best for you or for your caregiver to inject Aranesp. Your doctor, nurse, or pharmacist will show you how to administer the injection using the pre-filled syringe.
Do not attempt to inject yourself if you have not been properly trained. Never inject Aranesp into a vein by yourself.

If you have chronic kidney failure
For all adult and pediatric patients aged ≥ 1 year with chronic kidney failure, Aranesp is administered as a single injection either under the skin (subcutaneously) or into a vein (intravenously).
The initial dose of Aranesp per kilogram of body weight to correct anaemia is:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once weekly. For adult patients not on dialysis, 1.5 micrograms/kg once monthly may also be used as the initial dose.

All adult and pediatric patients aged ≥ 1 year with chronic kidney failure will continue to receive Aranesp after correction of anaemia as a single injection either once weekly or once every two weeks. For all adult patients and pediatric patients aged ≥ 11 years not on dialysis, Aranesp may also be administered as a single injection once monthly.
Your doctor will regularly perform blood tests to monitor how your anaemia is responding and may adjust the dose every four weeks as needed to maintain long-term control of anaemia.
Your doctor will use the lowest effective dose to control the symptoms of anaemia.
If you do not respond adequately to Aranesp, your doctor will check the dose and inform you if adjustments to your Aranesp dosage are necessary.
Your blood pressure will also be monitored regularly, especially at the beginning of treatment.
In some cases, your doctor may recommend that you take iron supplements.
Your doctor may decide to change the route of administration (from subcutaneous to intravenous or vice versa). If such a change is made, the same dose as previously used will be maintained initially, and your doctor will perform blood tests to ensure that your anaemia continues to be properly managed.
If your doctor decides to switch your treatment from r-HuEPO (recombinant human erythropoietin produced by genetic technology) to Aranesp, they will determine whether Aranesp should be administered once weekly or once every two weeks. The route of administration will remain the same as for r-HuEPO, but your doctor will inform you of the dose and timing, and may adjust the dose as necessary.

If you are receiving chemotherapy
Aranesp is administered once weekly or once every three weeks as a single subcutaneous injection.
The initial dose to correct anaemia is:

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight); or
• 2.25 micrograms per kilogram of body weight once weekly.

Your doctor will regularly perform blood tests to monitor your response to treatment and may adjust the dose as needed. Treatment will continue for approximately four weeks after the end of the chemotherapy cycle. Your doctor will inform you exactly when to stop taking Aranesp.
In some cases, your doctor may recommend that you take iron supplements.

If you use more Aranesp than you should
You may experience serious problems if you use more Aranesp than required, such as very high blood pressure. If this occurs, contact your doctor, nurse, or pharmacist. If you feel unwell, seek immediate medical advice from your doctor, nurse, or pharmacist.

If you forget to use Aranesp
Do not take a double dose to make up for a missed dose.
If you have missed a dose of Aranesp, contact your doctor to determine when you should administer the next injection.

If you stop using Aranesp
If you wish to stop using Aranesp, you must first discuss this with your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Following administration of Aranesp, some patients have experienced the following side effects:

Patients with chronic renal failure

Very common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions

Common: may affect up to 1 in 10 people

• Stroke
• Pain at the injection site
• Skin rashes and/or redness of the skin

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Seizures (epileptic fits)
• Bruising and bleeding at the injection site
• Blood clots in a dialysis access site

Not known: frequency cannot be estimated from the available data

• Pure red cell aplasia (PRCA) - (anaemia, unusual tiredness, loss of strength)

Patients with tumours

Very common: may affect more than 1 in 10 people

• Allergic reactions

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Skin rashes and/or redness of the skin
• Fluid retention (oedema)

Uncommon: may affect up to 1 in 100 people

• Seizures (epileptic fits)
• Bruising and bleeding at the injection site

All patients

Not known: frequency cannot be estimated from the available data

• Severe allergic reactions which may include:
• Sudden allergic reactions which may be fatal (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may make swallowing or breathing difficult (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rashes
• Hives (urticaria)

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with treatment with epoetin. These may present with reddish patches or circular spots, often with central blisters, on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. If you experience these symptoms, stop taking Aranesp immediately and contact your doctor or seek immediate medical attention (see section 2).

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aranesp

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pre-filled syringe after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not use Aranesp if you think it has been frozen.
Keep the pre-filled syringe in the outer packaging to protect it from light.
Once the syringe has been removed from the refrigerator and allowed to reach room temperature for about 30 minutes prior to injection, it must be used within 7 days or must be discarded.
Do not use this medicine if you notice that the solution in the pre-filled syringe is cloudy or contains visible particles.
Do not dispose of any medicine via waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Aranesp contains

• The active substance is darbepoetin alfa, r-HuEPO (recombinant human erythropoietin produced by genetic engineering). The pre-filled syringe contains 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300 or 500 micrograms of darbepoetin alfa.
• The other components are monosodium phosphate, disodium phosphate, sodium chloride, polysorbate 80 and water for injections.

Description of the appearance of Aranesp and contents of the pack
Aranesp is a clear, colourless or slightly opalescent injectable solution in a pre-filled syringe.
Aranesp is available in packs of 1 or 4 pre-filled syringes. The syringes are packaged with or without blisters (packs of 1 or 4 syringes) or without blisters (packs of 1 syringe). Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tel/Tél: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tel/Tél: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen B.V.
Tlf: +45 39617500 The Netherlands
Tel: +31 (0)76 5732500

Deutschland Nederland
AMGEN GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tel: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2°321°114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121 i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100

Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 257 25888 Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

7. Instructions for injecting Aranesp pre-filled syringe

This section contains information on how to self-administer an injection of Aranesp. It is important that
you do not attempt to give yourself the injection unless you have been properly instructed by your
doctor, nurse, or pharmacist. If you have any questions about the injection method, please consult your
doctor, nurse, or pharmacist for assistance.
How should you or the person administering the injection use the Aranesp pre-filled syringe?
Your doctor has prescribed Aranesp in a pre-filled syringe for injection into the tissue just under the
skin. Your doctor, nurse, or pharmacist will inform you of the amount of Aranesp you need and how
often you should inject it.
What you need:
To administer an injection, you will need:

• a new pre-filled syringe of Aranesp; and
• alcohol swabs or similar disinfectants.

What should I do before giving myself a subcutaneous injection of Aranesp?

1. Remove the pre-filled syringe from the refrigerator. Leave the pre-filled syringe at room temperature for about 30 minutes. This will make the injection more comfortable. Do not heat Aranesp in any other way (for example, in a microwave or in warm water). Also, do not leave the syringe exposed to direct sunlight.
2. Do not shake the pre-filled syringe.
3. Do not remove the needle cap from the syringe until you are ready to give the injection.
4. Check that the dosage is exactly the one prescribed by your doctor.
5. Check the expiry date on the label of the pre-filled syringe (EXP). Do not use it if the date is after the last day of the month indicated.
6. Check the appearance of Aranesp. It should be a clear, colourless or slightly opalescent liquid. If it is cloudy or if particles are visible, do not use it.

7. Wash your hands thoroughly.

8. Find a comfortable, well-lit, clean surface and have everything you need within reach.

How do I prepare the Aranesp injection?
Before administering your Aranesp injection, you must carry out the following steps:

1. To avoid bending the needle, gently remove the needle cap without twisting, as shown in figures 1 and 2.
2. Do not touch the needle and do not push the plunger.
3. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before giving the injection. Injecting the solution with the air bubble present is harmless.
4. You can now use the pre-filled syringe.

Where should I give myself the injection?

The most suitable sites for self-injection are the upper thighs and the abdominal area. If someone else is giving you the injection, the back of the upper arms may also be used.
Change the injection site if you notice redness or tenderness in the area.

How do I give myself the injection?

1. Clean the skin using the alcohol swab and gently pinch the skin between your thumb and forefinger (without compressing it too tightly).
2. Insert the needle completely into the skin as demonstrated to you by your doctor, nurse, or pharmacist.
3. Inject the prescribed dose subcutaneously as directed by your doctor, nurse, or pharmacist.
4. Push the plunger slowly and steadily, keeping the skin pinched, until the syringe is empty.
5. Remove the needle and release the skin.
6. If you see a drop of blood, gently press a cotton ball or gauze pad on the injection site. Do not rub the injection site. If needed, you may cover the injection site with an adhesive bandage.
7. Use each syringe only once. Do not reuse any Aranesp remaining in the syringe.

To remember: If you have any problems, do not hesitate to consult your doctor or nurse for help or advice.

Disposal of used syringes

• Do not recap used needles, as you might accidentally prick yourself.
• Keep used syringes out of sight and reach of children.
• Used pre-filled syringes must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

Package leaflet: information for the user

Aranesp 10 micrograms injectable solution in pre-filled pen (SureClick), 15 micrograms injectable solution in pre-filled pen (SureClick), 20 micrograms injectable solution in pre-filled pen (SureClick), 30 micrograms injectable solution in pre-filled pen (SureClick), 40 micrograms injectable solution in pre-filled pen (SureClick), 50 micrograms injectable solution in pre-filled pen (SureClick), 60 micrograms injectable solution in pre-filled pen (SureClick), 80 micrograms injectable solution in pre-filled pen (SureClick), 100 micrograms injectable solution in pre-filled pen (SureClick), 130 micrograms injectable solution in pre-filled pen (SureClick), 150 micrograms injectable solution in pre-filled pen (SureClick), 300 micrograms injectable solution in pre-filled pen (SureClick), 500 micrograms injectable solution in pre-filled pen (SureClick)

darbepoetin alfa
Please read this entire leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse (see section 4).

Contents of this leaflet:

1. What Aranesp is and what it is used for
2. What you need to know before using Aranesp
3. How to use Aranesp
4. Possible side effects
5. How to store Aranesp
6. Contents of the pack and other information

1. What Aranesp is and what it is used for

Your doctor has prescribed Aranesp (an anti-anaemic agent) to treat your anaemia. Anaemia occurs
when there are not enough red blood cells in the blood, and symptoms of anaemia may include
fatigue, weakness, and shortness of breath.
Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is
produced by the kidneys and stimulates the bone marrow to produce a greater number of red blood cells. The
active substance in Aranesp is darbepoetin alfa, produced by genetic engineering in Chinese hamster ovary cells (CHO-K1).
If you have chronic renal failure
Aranesp is used to treat symptomatic anaemia associated with chronic renal failure in adults and children. In renal failure, the kidneys do not produce sufficient amounts of the natural hormone erythropoietin, which can often lead to anaemia.
It will take some time for your body to produce more red blood cells, so it may take about four weeks before you notice any effect. The effectiveness of Aranesp in treating anaemia is not affected by routine dialysis procedures.
If you are receiving chemotherapy
Aranesp is used to treat symptomatic anaemia in adult patients with non-myeloid tumours (non-myeloid neoplasms) who are receiving chemotherapy.
One of the main side effects of chemotherapy is that it prevents the bone marrow from producing enough blood cells. Towards the end of chemotherapy treatment, especially if you have received intensive chemotherapy, the number of red blood cells may decrease, causing anaemia.

2. What you need to know before using Aranesp

Do not use Aranesp

• if you are allergic to darbepoetin alfa or to any of the other ingredients of this medicine listed in section 6;
• if you have been diagnosed with high blood pressure that is not currently controlled with other medicines prescribed by your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Aranesp.
Inform your doctor if you have or have had:

• high blood pressure currently controlled with medicines prescribed by your doctor;
• sickle cell anemia;
• epileptic seizures (fits);
• seizures (fits or attacks);
• liver disease;
• a marked lack of response to medicines used to treat anemia;
• allergy to latex (the needle cap of the pre-filled pen contains a latex derivative); or
• hepatitis C.

Special warnings:

• If you experience symptoms such as unusual tiredness and loss of strength, you may have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that your body stops or reduces the production of red blood cells, leading to severe anemia. If you experience these symptoms, inform your doctor, who will decide on the best treatment strategy for your anemia.
• Be especially careful if you are taking other medicines that stimulate red blood cell production: Aranesp belongs to a group of products that stimulate red blood cell production, like human erythropoietin. Your healthcare provider must always record the correct name of the medicine you are taking.
• If you have chronic kidney failure and, in particular, do not respond appropriately to Aranesp, your doctor will monitor your Aranesp dose carefully, because repeated dose increases of Aranesp in case of inadequate response to treatment may increase the risk of heart or blood vessel problems and could increase the risks of heart attack, stroke, and death.
• Your doctor should aim to maintain your hemoglobin level between 10 and 12 g/dL. Your doctor will monitor to ensure that your hemoglobin level does not exceed a certain threshold, as high hemoglobin levels may increase your risk of heart or blood vessel problems and could increase the risks of heart attack, stroke, and death.
• If you experience symptoms such as severe headache, drowsiness, confusion, vision problems, nausea, vomiting, or seizures, this may indicate very high blood pressure. If you experience these symptoms, contact your doctor immediately.
• If you have a tumor, you should know that Aranesp can act as a growth factor for blood cells and, in some circumstances, may have negative effects on the tumor. Depending on your specific situation, a blood transfusion may be preferable. Discuss this with your doctor.
• Improper use by healthy individuals may cause heart and blood vessel problems that pose an immediate life-threatening risk.
• Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported during treatment with epoetin. SJS/TEN may initially appear as reddish or circular patches, often with central blisters, on the trunk. Mouth, throat, nose, genital, and eye ulcers (swollen and red eyes) may also occur. These serious skin reactions are often preceded by fever and/or flu-like symptoms. Skin rashes may progress to widespread skin peeling and life-threatening complications. If you develop a severe skin rash or any of these other skin symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention.

Other medicines and Aranesp
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The medicines cyclosporine and tacrolimus (medicines that suppress the immune system) may be affected by the number of red blood cells in your blood. It is important that you inform your doctor if you are taking any of these medicines.

Aranesp with food and drink
Food and drink do not affect Aranesp.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Aranesp has not been studied in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you think you may be pregnant; or
• you are planning a pregnancy.

It is not known whether darbepoetin alfa is excreted in breast milk. If you use Aranesp, you must stop breastfeeding.

Driving and using machines
Aranesp is unlikely to affect your ability to drive or operate machinery.

Aranesp contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially ‘sodium-free’.

3. How to use Aranesp

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Based on certain blood tests, your doctor has determined that you need Aranesp because your haemoglobin level is 10 g/dL or lower. The injection must be administered under the skin (subcutaneously), so you can use the pre-filled Aranesp pen. Your doctor will inform you about the amount and frequency of Aranesp doses required to maintain a haemoglobin level between 10 and 12 g/dL. This may vary depending on whether you are an adult or a child.

How to self-administer Aranesp injection
Your doctor has decided that the pre-filled Aranesp pen is the best way for you, a nurse, or your caregiver to administer Aranesp. Your doctor, nurse, or pharmacist will show you how to inject Aranesp using the pre-filled pen. Do not attempt to inject yourself if you have not been properly trained. Never inject Aranesp into a vein by yourself. The pre-filled pen is designed only for subcutaneous injection (under the skin).

For instructions on how to use the pre-filled pen, please read the section at the end of this leaflet.

If you have chronic kidney failure
For all adult and paediatric patients aged ≥ 1 year with chronic kidney failure, Aranesp in the pre-filled pen is administered as a single subcutaneous injection.

The initial dose of Aranesp per kilogram of body weight to correct anaemia will be:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once weekly. For adult patients not on dialysis, 1.5 micrograms/kg once monthly may also be used as the initial dose.

Once anaemia has been corrected in all adult and paediatric patients aged ≥ 1 year with chronic kidney failure, treatment will continue with Aranesp as a single injection either once weekly or once every two weeks. For all adult patients and paediatric patients aged ≥ 11 years not on dialysis, Aranesp may also be administered once monthly.

Your doctor will regularly perform blood tests to monitor how your anaemia is responding and may adjust your dose every four weeks as needed to maintain long-term control of anaemia.
Your doctor will use the lowest effective dose to control the symptoms of anaemia.
If you do not respond adequately to Aranesp, your doctor will review your dose and inform you if adjustments to your Aranesp dosage are necessary.
Your blood pressure will also be monitored regularly, especially at the beginning of treatment.
In some cases, your doctor may recommend that you take iron supplements.
Your doctor may decide to change the route of administration (from subcutaneous to intravenous or vice versa). If the route of administration is changed, treatment will start with the same dose previously received, and your doctor will perform blood tests to ensure that anaemia continues to be properly managed.
If your doctor decides to switch your treatment from r-HuEPO (recombinant human erythropoietin) to Aranesp, they will determine the frequency of Aranesp injections—either once weekly or once every two weeks. The route of administration will remain the same as for r-HuEPO, but your doctor will instruct you on the correct dose and timing and may adjust the dose if necessary.

If you are receiving chemotherapy
Aranesp is administered once weekly or once every three weeks as a single subcutaneous injection.

The initial dose to correct anaemia will be:

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight); or
• 2.25 micrograms per kilogram of body weight (once weekly).

Your doctor will perform regular blood tests to monitor your response to treatment and may adjust your dose as needed. Treatment will continue for approximately four weeks after the end of your chemotherapy cycle. Your doctor will inform you exactly when to stop taking Aranesp.
In some cases, your doctor may recommend that you take iron supplements.

If you use more Aranesp than you should
You may experience serious problems if you take more Aranesp than required, such as very high blood pressure. If this happens, contact your doctor, nurse, or pharmacist immediately. If you feel unwell, seek medical advice from your doctor, nurse, or pharmacist without delay.

If you forget to use Aranesp
Do not take a double dose to make up for a missed dose.
If you have missed a dose of Aranesp, contact your doctor to determine when you should administer the next injection.

If you stop using Aranesp
If you wish to discontinue treatment with Aranesp, you must discuss this first with your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Following administration of Aranesp, some patients have experienced the following side effects:

Patients with chronic renal failure

Very common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions

Common: may affect up to 1 in 10 people

• Stroke
• Pain at the injection site
• Skin rashes and/or redness of the skin

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Seizures (epileptic fits)
• Bruising and bleeding at the injection site
• Blood clots in a dialysis access site

Not known: frequency cannot be estimated from the available data

• Pure red cell aplasia (PRCA) - (anaemia, unusual tiredness, loss of strength)

Patients with tumours

Very common: may affect more than 1 in 10 people

• Allergic reactions

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Skin rashes and/or redness of the skin
• Fluid retention (oedema)

Uncommon: may affect up to 1 in 100 people

• Seizures (epileptic fits)
• Bruising and bleeding at the injection site

All patients

Not known: frequency cannot be estimated from the available data

• Severe allergic reactions which may include:
• Sudden allergic reactions which may be fatal (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may make swallowing or breathing difficult (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rashes
• Hives (urticaria)

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with epoetin treatment. These may present with reddish patches or circular spots, often with central blisters, on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. If you experience these symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention (see section 2).

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aranesp

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pre-filled pen after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not use Aranesp if you think it has been frozen.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.
Once the pre-filled pen has been removed from the refrigerator and allowed to reach room temperature for about 30 minutes before injection, it must be used within 7 days or must be discarded.
Do not use this medicine if you notice that the solution in the pre-filled pen is cloudy or contains visible particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Pack contents and other information

What Aranesp contains

• The active substance is darbepoetin alfa, r-HuEPO (recombinant human erythropoietin produced by genetic engineering). The pre-filled pen contains 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300 or 500 micrograms of darbepoetin alfa.
• The other ingredients are monobasic sodium phosphate, dibasic sodium phosphate, sodium chloride, polysorbate 80 and water for injections.

Description of the appearance of Aranesp and contents of the pack
Aranesp is a clear, colourless or slightly opalescent injectable solution in a pre-filled pen.
Aranesp (SureClick) is available in packs of 1 or 4 pre-filled pens. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tel/Tél: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tel/Tél: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen B.V.
Tlf: +45 39617500 The Netherlands
Tel: +31 (0)76 5732500

Deutschland Nederland
AMGEN GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tel: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial i Finland
Tel: +39 02 6241121 Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100

Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 257 25888 Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

Instructions for use

It is important not to attempt to perform the injection yourself without first being trained by a healthcare professional.
Additional educational materials are available to instruct you on self-administration of Aranesp in the pre-filled pen, a practice demonstration device, and poster-format instructions for patients/caregivers with reduced vision.
Guide to parts
Before use After use
Red start button

Expiry date
Expiry date
Plunger (may be
visible in the window;
position may vary) Yellow window
(injection
Window completed)
Medication
Yellow safety
Yellow safety
device (needle
device (needle
inside)
inside)
Grey cap
Grey cap removed
inserted
Important: Needle inside the yellow safety device.
Important
Before using the Aranesp SureClick pre-filled pen, read the following important information:
Storage of Aranesp SureClick pre-filled pens

• Keep the pre-filled pen and all medicines out of the sight and reach of children.
• Keep the pre-filled pen in its original packaging to protect it from light or physical damage.
• Store the pre-filled pen in the refrigerator (2°C - 8°C).
• Once the pre-filled pen has been removed from the refrigerator and left at room temperature (up to 25°C) for about 30 minutes before injection, it must be used within seven days or discarded. Do not store the pre-filled pen in hot or cold environments. For example, avoid storing it

in the car dashboard or trunk.
Do not freeze. Do not use Aranesp if you think it has been frozen.

How to use the Aranesp SureClick pre-filled pens

• Your healthcare professional has prescribed Aranesp pre-filled syringe for injection into the tissue beneath the skin (subcutaneous use). Do not use the pre-filled pen beyond the expiry date shown on the label. The expiry date refers to the last day of the month.
  Do not shake the pre-filled pen.

Do not remove the grey cap from the pre-filled pen unless you are ready to perform the injection.
Do not use the pre-filled pen if it has fallen on a hard surface. Some parts of the pen may be broken even if the damage is not visible. Use a new pre-filled pen.

• The grey cap on the pen contains dry natural rubber, a latex derivative. If you are allergic to latex, inform your healthcare professional. For further information or assistance, contact your healthcare professional.

Step 1: Preparation
A Remove one pre-filled pen from the packaging.
Remove the pre-filled pen from the packaging vertically and carefully.
Return the original packaging with unused pre-filled pens to the refrigerator.
Allow the pre-filled pen to reach room temperature for at least 30 minutes before injection.

Do not return the pre-filled pen to the refrigerator once it has reached room temperature.
Do not try to warm the pre-filled pen using heat sources such as hot water or a microwave oven.
Do not expose the pre-filled pen to direct sunlight.

Do not shake the pre-filled pen.
Do not remove the grey cap from the pre-filled pen yet.

B Check the pre-filled pen.

Grey cap inserted Medication Window Plunger
(needle inside) (position may vary)
Ensure that the medication in the window is a clear, colourless liquid.

• Check that it is the correct dose prescribed by your healthcare professional.
• You may see the plunger in a different position in the inspection window, depending on the dose.

Do not use the pre-filled pen if the medication is cloudy, discoloured, or contains large clumps, fragments, or particles.
Do not use the pre-filled pen if any part appears cracked or broken.

Do not use the pre-filled pen if the grey cap is missing or not securely attached.
Do not use the pre-filled pen if the expiry date printed after Exp. on the label has passed.
In any of these cases, use a new pre-filled pen and contact your healthcare professional.
C Prepare everything needed to perform the injection.
Wash your hands thoroughly with soap and water.
On a clean, well-lit surface, prepare:

• A new pre-filled pen
• Alcohol swabs
• A cotton ball or gauze pad
• A plaster
• A sharps disposal container

D Prepare and clean the injection site.

Upper arm
Abdomen
Thigh
You may use:

• The thigh.

• The abdomen, except for the area within 5 centimetres around the navel.

• The outer upper arm (only if someone else is administering the injection). Clean the injection site with an alcohol swab. Allow the skin to dry. Do not touch this area again before performing the injection.

• For each injection, choose a different site. If it is necessary to use the same injection site, ensure you do not inject in the same spot as the previous time. Do not inject into areas where the skin is tender, bruised, red, or hardened.

• Avoid injecting into raised, thickened, red, or scaly skin patches, lesions, or areas with scars or stretch marks.

Important: Follow the instructions provided by your healthcare professional on selecting appropriate injection sites and rotating sites for each injection.
Step 2: Preparation for injection
E Remove the grey cap by pulling it horizontally only when you are ready to perform the injection. Do not leave the pen without the grey cap for more than five minutes, as this may cause the medication to dry out.

It is normal to see a drop of liquid at the tip of the needle or on the yellow safety device.
Do not rotate or bend the grey cap.

Do not reattach the grey cap to the pre-filled pen.
Do not remove the grey cap from the pre-filled pen unless you are ready to perform the injection.

If you are unable to perform the injection, contact your healthcare professional immediately.
F Stretch or pinch the skin at the injection site to create a stable surface.
Stretching method

Stretch the skin firmly by moving the thumb and fingers in opposite directions to create an area about 5 centimetres wide.
Or
Pinch method

Firmly grasp a section of skin with the thumb and fingers to form a fold about 5 centimetres wide.
Important: It is important to keep the skin stretched or pinched during the injection.
Step 3: Injection
G Keep the skin stretched or pinched. After removing the grey cap, place the pre-filled pen on the skin at a 90-degree angle.

Important: Do not press the red start button yet.
H Press the pre-filled pen firmly against the skin until it stops moving.
The yellow safety device retracts when pressed against a taut injection site.

Yellow safety device retracted.
Important: Press the pre-filled pen down as far as possible, but do not press the red start button until you are ready to administer the injection.
I As soon as you are ready to administer the injection, press the red start button.

J Continue to press the pre-filled pen down against the skin. The injection may take about 15 seconds.

15 seconds

After the injection is
complete, the window
will turn yellow

Note: After lifting the pre-filled pen from the skin, the needle will automatically cover.
Important: Once the pre-filled pen is removed, if the window has not turned yellow or it appears that the medication is still being injected, this means you have not received a complete dose. Contact your healthcare professional immediately.
K Examine the injection site.

• If you see blood, apply gentle pressure with a cotton ball or gauze pad to the injection site. Do not rub the injection site. If needed, apply a plaster.

Step 4: Final step
L Dispose of the pre-filled pen and the grey cap.

Dispose of the pre-filled pen in the sharps disposal container immediately after use.
Do not reuse the pre-filled pen.

Do not recycle the pre-filled pen or the sharps disposal container or dispose of them in household waste.
Ask your healthcare professional for the proper method of disposal, as there may be specific local guidelines.
Important: Keep the sharps disposal container out of the sight and reach of children.

Package leaflet: information for the user

Aranesp 10 micrograms solution for injection in pre-filled syringe, 15 micrograms solution for injection in pre-filled syringe, 20 micrograms solution for injection in pre-filled syringe, 30 micrograms solution for injection in pre-filled syringe, 40 micrograms solution for injection in pre-filled syringe, 50 micrograms solution for injection in pre-filled syringe, 60 micrograms solution for injection in pre-filled syringe, 80 micrograms solution for injection in pre-filled syringe, 100 micrograms solution for injection in pre-filled syringe, 130 micrograms solution for injection in pre-filled syringe, 150 micrograms solution for injection in pre-filled syringe, 300 micrograms solution for injection in pre-filled syringe, 500 micrograms solution for injection in pre-filled syringe

darbepoetin alfa
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse (see section 4).

Contents of this leaflet

1. What Aranesp is and what it is used for
2. What you need to know before using Aranesp
3. How to use Aranesp
4. Possible side effects
5. How to store Aranesp
6. Contents of the pack and other information

1. What Aranesp is and what it is used for

Your doctor has prescribed Aranesp (an anti-anaemic agent) to treat your anaemia. You have anaemia
when there is not enough red blood cells in your blood, and symptoms of anaemia may include
fatigue, weakness, and shortness of breath.
Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is
produced by the kidneys and stimulates the bone marrow to produce more red blood cells. The
active substance in Aranesp is darbepoetin alfa, produced by genetic engineering techniques in
Chinese hamster ovary cells (CHO-K1).
If you have chronic renal failure
Aranesp is used to treat symptomatic anaemia associated with chronic renal failure in adults and
children. In renal failure, the kidneys do not produce enough of the natural hormone erythropoietin,
which can often cause anaemia.
It will take some time for your body to produce more red blood cells, so it will take about four weeks
before you notice any effect. The effectiveness of Aranesp in treating anaemia is not affected by
routine dialysis procedures.
If you are receiving chemotherapy
Aranesp is used to treat symptomatic anaemia in adult patients with non-myeloid tumours (non-myeloid
neoplasms) who are receiving chemotherapy.
One of the main side effects of chemotherapy is that it prevents the bone marrow from producing
enough blood cells. Towards the end of chemotherapy treatment, especially if you have received
intensive chemotherapy, the number of red blood cells may decrease, causing anaemia.

2. What you should know before using Aranesp

Do not use Aranesp

• if you are allergic to darbepoetin alfa or to any of the other ingredients of this medicine listed in section 6;
• if you have been diagnosed with high blood pressure that is not currently controlled with other medicines prescribed by your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Aranesp.
Inform your doctor if you have or have had:

• high blood pressure that is currently controlled with medicines prescribed by your doctor;
• sickle cell anemia;
• epileptic seizures (convulsions);
• convulsions (seizures or fits);
• liver disease;
• a significant lack of response to medicines used to treat anemia;
• allergy to latex (the needle cap of the pre-filled syringe contains a latex derivative); or
• hepatitis C.

Special warnings:

• If you experience symptoms including unusual tiredness and loss of strength, you may have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that your body stops or reduces the production of red blood cells, leading to severe anemia. If you experience these symptoms, inform your doctor, who will decide on the best treatment strategy for your anemia.
• Be especially careful if you are taking other medicines that stimulate red blood cell production: Aranesp belongs to a group of products that stimulate red blood cell production, like human erythropoietin. Your healthcare provider must always record the correct name of the medicine you are taking.
• If you have chronic renal failure and, in particular, do not respond adequately to Aranesp, your doctor will review your Aranesp dose, because repeated dose increases of Aranesp in case of non-response to treatment may increase the risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• Your doctor should aim to keep your hemoglobin level between 10 and 12 g/dL. Your doctor will monitor to ensure that your hemoglobin level does not exceed a specific threshold, as high hemoglobin levels may increase your risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• If you experience symptoms such as severe headache, drowsiness, confusion, vision problems, nausea, vomiting, or convulsions, this may indicate very high blood pressure. If you experience these symptoms, contact your doctor immediately.
• If you have a tumor, you should know that Aranesp may act as a growth factor for blood cells and, in certain circumstances, may have negative effects on the tumor. Depending on your specific situation, a blood transfusion may be preferable. Discuss this with your doctor.
• Improper use by healthy individuals may cause heart and vascular problems that pose an immediate threat to life.
• Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with epoetin treatment. SJS/TEN may initially appear as reddish or circular patches, often with central blisters, on the trunk. Mouth, throat, nose, genital, and eye ulcers (swollen and red eyes) may also occur. These serious skin rashes are often preceded by fever and/or flu-like symptoms. The skin reactions may progress to widespread skin peeling and life-threatening complications. If you develop a severe skin rash or any of these other skin symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention.

Other medicines and Aranesp
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Cyclosporine and tacrolimus (medicines that suppress the immune system) may be affected by the number of red blood cells in the blood. It is important that you inform your doctor if you are taking either of these medicines.

Aranesp with food and drink
Food and drink do not affect Aranesp.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Aranesp has not been studied in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you think you might be pregnant; or
• you are planning a pregnancy.

It is not known whether darbepoetin alfa is excreted in breast milk. If you use Aranesp, you must stop breastfeeding.

Driving and using machines
Aranesp should not affect your ability to drive or operate machinery.

Aranesp contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to use Aranesp

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Based on certain blood tests, your doctor has determined that you need Aranesp because your haemoglobin level is 10 g/dL or lower. Your doctor will inform you about the amount and frequency of Aranesp administration in order to maintain a haemoglobin level between 10 and 12 g/dL.
This may vary depending on whether you are an adult or a child.

How to self-administer Aranesp injections
Your doctor may decide it is best for you or for your caregiver to inject Aranesp. Your doctor, nurse, or pharmacist will show you how to administer the injection using the pre-filled syringe.
Do not attempt to inject yourself unless you have been properly trained. Never inject Aranesp into a vein by yourself.

If you have chronic renal failure
For all adult and paediatric patients aged ≥ 1 year with chronic renal failure, Aranesp is administered as a single subcutaneous (under the skin) or intravenous (into a vein) injection.
The initial dose of Aranesp per kilogram of body weight to correct anaemia is:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once weekly. For adult patients not on dialysis, 1.5 micrograms/kg once monthly may also be used as the initial dose.

All adult and paediatric patients aged ≥ 1 year with chronic renal failure will continue to receive Aranesp as a single injection either once weekly or once every two weeks after correction of anaemia. For all adult patients and paediatric patients aged ≥ 11 years not on dialysis, Aranesp may also be administered as a single injection once monthly.
Your doctor will perform regular blood tests to monitor how your anaemia is responding and may adjust your dose every four weeks as needed to maintain long-term control of anaemia.
Your doctor will use the lowest effective dose to control the symptoms of anaemia.
If you do not respond adequately to Aranesp, your doctor will review your dose and inform you if adjustments to the Aranesp dosage are necessary.
Your blood pressure will also be monitored regularly, especially at the beginning of treatment.
In some cases, your doctor may recommend that you take iron supplements.
Your doctor may decide to change the route of administration (subcutaneous or intravenous). If the route of administration is changed, treatment will begin with the same dose previously administered, and your doctor will perform blood tests to ensure that anaemia continues to be properly managed.
If your doctor decides to switch your treatment from r-HuEPO (recombinant human erythropoietin) to Aranesp, they will determine the frequency of Aranesp administration—either once weekly or once every two weeks. The route of administration will remain the same as for r-HuEPO, but your doctor will inform you of the dose and timing and may adjust the dose as necessary.

If you are receiving chemotherapy
Aranesp is administered once weekly or once every three weeks as a single subcutaneous injection.
The initial dose to correct anaemia is:

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight); or
• 2.25 micrograms per kilogram of body weight once weekly.

Your doctor will perform regular blood tests to monitor your response to treatment and may adjust your dose as needed. Treatment will continue for approximately four weeks after the end of the chemotherapy cycle. Your doctor will inform you exactly when to stop taking Aranesp.
In some cases, your doctor may recommend that you take iron supplements.

If you use more Aranesp than you should
You may experience serious problems if you take more Aranesp than required, such as very high blood pressure. If this occurs, contact your doctor, nurse, or pharmacist. If you feel unwell, seek immediate medical advice from your doctor, nurse, or pharmacist.

If you forget to use Aranesp
Do not take a double dose to make up for a missed dose.
If you miss a dose of Aranesp, contact your doctor to determine when you should administer the next injection.

If you stop using Aranesp
If you wish to stop treatment with Aranesp, you must discuss this first with your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Following administration of Aranesp, some patients have experienced the following side effects:

Patients with chronic kidney disease

Very common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions

Common: may affect up to 1 in 10 people

• Stroke
• Pain at the injection site
• Skin rashes and/or redness of the skin

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Seizures (epileptic fits)
• Bruising and bleeding at the injection site
• Blood clots in a dialysis access site

Not known: frequency cannot be estimated from the available data

• Pure red cell aplasia (PRCA) - (anaemia, unusual tiredness, loss of strength)

Patients with cancer

Very common: may affect more than 1 in 10 people

• Allergic reactions

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Skin rashes and/or redness of the skin
• Fluid retention (oedema)

Uncommon: may affect up to 1 in 100 people

• Seizures (epileptic fits)
• Bruising and bleeding at the injection site

All patients

Not known: frequency cannot be estimated from the available data

• Severe allergic reactions which may include:
• Sudden allergic reactions that may be fatal (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may make swallowing or breathing difficult (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rashes
• Hives (urticaria)

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with treatment with epoetin. These may present with reddish patches or circular spots, often with central blisters, on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. If you experience these symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention (see section 2).

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aranesp

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the pre-filled syringe after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not use Aranesp if you think it has been frozen.
Keep the pre-filled syringe in its outer packaging to protect the medicine from light.
Once the syringe has been removed from the refrigerator and allowed to reach room temperature for about 30 minutes before injection, it must be used within 7 days or must be discarded.
Do not use this medicine if you notice that the solution in the syringe is cloudy or contains visible particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Aranesp contains

• The active substance is darbepoetin alfa, r-HuEPO (recombinant human erythropoietin produced by genetic engineering). The pre-filled syringe contains 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300 or 500 micrograms of darbepoetin alfa.
• The other components are monosodium phosphate, disodium phosphate, sodium chloride, polysorbate 80 and water for injections.

Description of the appearance of Aranesp and contents of the pack
Aranesp is a clear, colourless or slightly opalescent injectable solution in a pre-filled syringe.
Aranesp is available in packs containing 1 or 4 pre-filled syringes with automatic needle protection, with blister. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tel/Tél: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tel/Tél: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen B.V.
Tlf: +45 39617500 The Netherlands
Tel: +31 (0)76 5732500

Deutschland Nederland
AMGEN GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tel: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121 i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100

Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 257 25888 Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

Instructions for use:

Important
Before using an Aranesp pre-filled syringe with automatic needle protection, read
these important instructions:

• It is important that you do not attempt to perform the injection unless you have received proper instructions from your doctor or healthcare professional.
• Aranesp is administered as an injection into the tissue just beneath the skin (subcutaneous injection).
• Inform your doctor if you are allergic to latex. The needle cap on the pre-filled syringe contains a derivative of latex and may cause severe allergic reactions. Do not remove the grey needle cap from the pre-filled syringe until you are ready for
  the injection.
  Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new
  pre-filled syringe and contact your doctor or healthcare professional.
  Do not attempt to activate the pre-filled syringe before the injection.
  Do not attempt to remove the transparent safety shield from the pre-filled syringe.
  Do not attempt to remove the detachable label from the pre-filled syringe before administering
  the injection.
  Contact your doctor or healthcare professional with any questions.

For healthcare professionals only
Remove and retain the label from the prefilled syringe.

Rotate the plunger to move the label into a position where it can be removed.

Package leaflet: Information for the user

Aranesp 25 micrograms solution for injection in vial, 40 micrograms solution for injection in vial, 60 micrograms solution for injection in vial, 100 micrograms solution for injection in vial, 200 micrograms solution for injection in vial, 300 micrograms solution for injection in vial

darbepoetin alfa
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse (see section 4).

Contents of this leaflet

1. What Aranesp is and what it is used for
2. What you need to know before using Aranesp
3. How to use Aranesp
4. Possible side effects
5. How to store Aranesp
6. Contents of the pack and other information

1. What Aranesp is and what it is used for

Your doctor has prescribed Aranesp (an anti-anaemic agent) to treat your anaemia. You have anaemia
when there is not enough red blood cells in your blood, and symptoms of anaemia may include
fatigue, weakness, and shortness of breath.
Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is
produced by the kidneys and stimulates the bone marrow to produce a greater number of red blood cells. The
active substance of Aranesp is darbepoetin alfa, produced by genetic engineering in Chinese hamster ovary cells (CHO-K1).
If you have chronic renal failure
Aranesp is used to treat symptomatic anaemia associated with chronic renal failure in adults and children. In renal failure, the kidneys do not produce enough of the natural hormone erythropoietin, which can often cause anaemia.
It will take some time for your body to produce more red blood cells, so it will take about four weeks before you notice any effect. The effectiveness of Aranesp in treating anaemia is not affected by regular dialysis procedures.
If you are receiving chemotherapy
Aranesp is used to treat symptomatic anaemia in adult patients with non-myeloid tumours (non-myeloid neoplasms) who are receiving chemotherapy.
One of the main side effects of chemotherapy is that it prevents the bone marrow from producing enough blood cells. Towards the end of chemotherapy treatment, especially if you have received a large amount of chemotherapy, the number of red blood cells may decrease, causing you to become anaemic.

2. What you should know before using Aranesp

Do not use Aranesp

• if you are allergic to darbepoetin alfa or to any of the other ingredients of this medicine listed in section 6;
• if you have been diagnosed with high blood pressure that is not currently controlled with other medicines prescribed by your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Aranesp.
Inform your doctor if you have or have had:

• high blood pressure currently controlled with medicines prescribed by your doctor;
• sickle cell anemia;
• epileptic seizures (fits);
• seizures (fits or attacks);
• liver disease;
• marked lack of response to medicines used to treat anemia; or
• hepatitis C.

Special warnings:

• If you experience symptoms including unusual tiredness and loss of strength, you may have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that your body stops or reduces the production of red blood cells, leading to severe anemia. If you experience these symptoms, inform your doctor, who will decide the best treatment strategy for your anemia.
• Pay special attention if you are taking other medicines that stimulate red blood cell production: Aranesp belongs to a group of products that stimulate red blood cell production, similar to human erythropoietin. Healthcare professionals must always record the correct name of the medicine you are taking.
• If you have chronic kidney failure, and particularly if you do not respond adequately to Aranesp, your doctor will monitor your Aranesp dose carefully, because repeated dose increases of Aranesp in case of non-response to treatment may increase the risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• Your doctor should aim to maintain your hemoglobin level between 10 and 12 g/dL. Your doctor will ensure that your hemoglobin level does not exceed a specific threshold, as high hemoglobin levels may increase your risk of heart or blood vessel problems and could increase the risks of myocardial infarction, stroke, and death.
• If you experience symptoms such as severe headache, drowsiness, confusion, vision problems, nausea, vomiting, or seizures, this may indicate very high blood pressure. If you experience these symptoms, contact your doctor immediately.
• If you have a tumor, you should know that Aranesp can act as a growth factor for blood cells and, under certain circumstances, may have negative effects on the tumor. Depending on your specific situation, a blood transfusion may be preferable. Discuss this with your doctor.
• Improper use by healthy individuals may cause cardiac and vascular problems that pose an immediate life-threatening risk.
• Severe skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with epoetin treatment. SJS/TEN may initially appear as reddish or target-shaped rashes, often with central blisters, typically on the trunk. Mouth, throat, nose, genital, and eye ulcers (swollen and red eyes) may also occur. These severe skin reactions are often preceded by fever and/or flu-like symptoms. Skin rashes may progress to widespread skin peeling and life-threatening complications. If you develop a severe skin rash or any of these skin symptoms, stop taking Aranesp and contact your doctor or seek immediate medical attention.

Other medicines and Aranesp
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Medicines such as cyclosporine and tacrolimus (medicines that suppress the immune system) may be affected by changes in the number of red blood cells in the blood. It is important that you inform your doctor if you are taking any of these medicines.

Aranesp with food and drink
Food and drink do not affect Aranesp.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Aranesp has not been studied in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you think you may be pregnant; or
• you are planning a pregnancy.

It is not known whether darbepoetin alfa is excreted in breast milk. If you are using Aranesp, you must stop breastfeeding.

Driving and using machines
Aranesp should not affect your ability to drive or operate machinery.

Aranesp contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to use Aranesp

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Based on certain blood tests, your doctor has determined that you need Aranesp because your haemoglobin level is 10 g/dL or less. Your doctor will inform you of the amount and frequency of Aranesp administration required to maintain a haemoglobin level between 10 and 12 g/dL. This may vary depending on whether you are an adult or a child.
The injection will be administered by a healthcare professional.

If you have chronic renal failure
For all adult and paediatric patients aged ≥ 1 year with chronic renal failure, Aranesp is administered as a single subcutaneous (under the skin) or intravenous (into a vein) injection.
The initial dose of Aranesp per kilogram of body weight to correct anaemia will be:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once a week. For adult patients not on dialysis, 1.5 micrograms/kg once a month may also be used as the initial dose.

All adult and paediatric patients aged ≥ 1 year with chronic renal failure, once anaemia has been corrected, will continue to receive Aranesp as a single injection either once a week or once every two weeks. For all adult patients and paediatric patients aged ≥ 11 years not on dialysis, Aranesp may also be administered as an injection once a month.
Your doctor will regularly perform blood tests to monitor how your anaemia is responding and may adjust the dose every four weeks as needed to maintain long-term control of anaemia.
Your doctor will use the lowest effective dose to control the symptoms of anaemia.
If you do not respond adequately to Aranesp, your doctor will review the dose and inform you if adjustments to the Aranesp dosage are necessary.
Your blood pressure will also be monitored regularly, especially at the beginning of treatment.
In some cases, your doctor may recommend that you take iron supplements.
Your doctor may decide to change the route of administration (subcutaneous or intravenous). If the route of administration is changed, treatment will start with the same dose previously received, and your doctor will perform blood tests to ensure that anaemia continues to be properly managed.
If your doctor decides to switch your treatment from r-HuEPO (recombinant human erythropoietin) to Aranesp, they will also determine the frequency of Aranesp administration—either once a week or once every two weeks. The route of administration will be the same as that used for r-HuEPO, but your doctor will inform you of the dose and timing, and may adjust the dose if necessary.

If you are receiving chemotherapy
Aranesp is administered once a week or once every three weeks as a single subcutaneous injection.
The initial dose to correct anaemia will be:

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight); or
• 2.25 micrograms (once weekly) of Aranesp per kilogram of body weight.

Your doctor will perform regular blood tests to monitor your response to treatment and may adjust the dose as needed. Treatment will continue for approximately four weeks after the end of the chemotherapy cycle. Your doctor will inform you exactly when to stop taking Aranesp.
In some cases, your doctor may recommend that you take iron supplements.

If you use more Aranesp than you should
You may experience serious problems if you receive more Aranesp than required, such as very high blood pressure. If this occurs, contact your doctor, nurse, or pharmacist. If you feel unwell, seek immediate medical advice from your doctor, nurse, or pharmacist.

If you forget a dose of Aranesp
Do not take a double dose to make up for a missed dose.
If you forget a dose of Aranesp, contact your doctor to determine when you should receive the next dose.

If you stop treatment with Aranesp
If you wish to discontinue treatment with Aranesp, you must first discuss this with your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Following administration of Aranesp, some patients have experienced the following side effects:

Patients with chronic renal failure

Very common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions

Common: may affect up to 1 in 10 people

• Stroke
• Pain at the injection site
• Skin rashes and/or redness of the skin

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Seizures (epileptic fits)
• Bruising and bleeding at the injection site
• Blood clots in a dialysis access site

Not known: frequency cannot be estimated from the available data

• Pure red cell aplasia (PRCA) - (anaemia, unusual tiredness, loss of strength)

Patients with tumours

Very common: may affect more than 1 in 10 people

• Allergic reactions

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Skin rashes and/or redness of the skin
• Fluid retention (oedema)

Uncommon: may affect up to 1 in 100 people

• Seizures (epileptic fits)
• Bruising and bleeding at the injection site

All patients

Not known: frequency cannot be estimated from the available data

• Severe allergic reactions which may include:
• Sudden allergic reactions that may be fatal (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may make swallowing or breathing difficult (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rashes
• Hives (urticaria)

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with treatment with epoetin. These may present with reddish spots or circular patches, often with central blisters on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, and may be preceded by fever and flu-like symptoms. If you experience these symptoms, stop taking Aranesp immediately and contact your doctor or seek immediate medical attention (see section 2).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Aranesp

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the
vial after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Do not use Aranesp if you think it has been
frozen.
Keep the vial in the outer packaging to protect the medicine from light.
Once the vial has been removed from the refrigerator and left at room temperature for
about 30 minutes prior to injection, it must be used within 7 days or discarded.
Do not use this medicine if you notice that the solution in the vial is cloudy or if there are
visible particles in it.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Aranesp contains

• The active substance is darbepoetin alfa, r-HuEPO (recombinant human erythropoietin produced by genetic engineering). The vial contains 25, 40, 60, 100, 200 or 300 micrograms of darbepoetin alfa.
• The other components are monobasic sodium phosphate, dibasic sodium phosphate, sodium chloride, polysorbate 80 and water for injections.

Description of the appearance of Aranesp and contents of the pack
Aranesp is a clear, colourless or slightly opalescent injectable solution in a vial.
Aranesp is available in packs of 1 or 4 vials. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands
Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands
Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland
Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tel/Tél: +32 (0)2 7752711 Tel: +370 5 219 7474
България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tel/Tél: +32 (0)2 7752711
Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700
Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen B.V.
Tlf: +45 39617500 The Netherlands
Tel: +31 (0)76 5732500
Deutschland Nederland
AMGEN GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500
Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tel: +47 23308000
Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217
España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000
France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606
Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000
Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767
Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2°321°114 49
Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121 i Finland
Puh/Tel: +358 (0)9 54900500
Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100
Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 257 25888 Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu /
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.