Aranesp 40 micrograms solution for injection in a pre-filledsyringe

Your doctor has given you Aranesp (an anti-anaemic) to treat your anaemia. Anaemia is when your blood does not contain enough red blood cells and the symptoms may be fatigue, weakness and shortness of breath.

Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is produced in your kidneys and encourages your bone marrow to produce more red blood cells. The active substance of Aranesp is darbepoetin alfa produced by gene-technology in Chinese Hamster Ovary Cells (CHO-K1).

If you have chronic renal failure

Aranesp is used to treat symptomatic anaemia that is associated with chronic renal failure (kidney failure) in adults and children. In kidney failure, the kidney does not produce enough of the natural hormone erythropoietin which can often cause anaemia.

Because it will take your body some time to make more red blood cells, it will be about four weeks before you notice any effect. Your normal dialysis routine will not affect the ability of Aranesp to treat your anaemia.

If you are receiving chemotherapy

Aranesp is used to treat symptomatic anaemia in adult cancer patients with non-bone marrow cancers (non-myeloid malignancies) who are receiving chemotherapy.

One of the main side effects of chemotherapy is that it stops the bone marrow producing enough blood cells. Towards the end of your chemotherapy course, particularly if you have had a lot of chemotherapy, your red blood cell count may fall making you anaemic.

DO NOT use Aranesp:

• if you have been diagnosed with high blood pressure which is not being controlled with other medicines prescribed by your doctor; or
• if you are allergic to darbepoetin alfa, r-HuEPO (erythropoietin produced by gene technology) or to any of the other ingredients in Aranesp.

Take special care with Aranesp

Please tell your doctor if you are suffering or have suffered from:

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

Special warnings

• If you have symptoms which include unusual tiredness and a lack of energy this could mean you have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that the body has stopped or reduced the production of red blood cells which causes severe anaemia. If you experience these symptoms you should contact your doctor who will determine the best course of action to treat your anaemia.
• Take special care with other products that stimulate red blood cell production: Aranesp is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional should always record the exact product you are using.
• Your doctor should try to keep your haemoglobin between 10 and 12 g/dl. Your doctor will check that your haemoglobin does not exceed a certain level, as high haemoglobin concentrations could put you at risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.
• If you have chronic renal failure there is an increased risk of serious problems with your heart or blood vessels (cardiovascular events) if your haemoglobin is kept too high.
• If you have symptoms which include severe headache, drowsiness, confusion, problems with your eyesight, nausea, vomiting or fits (seizures), it could mean that you have very high blood

pressure. This has been reported in patients with chronic renal failure treated with Aranesp. If you experience these symptoms you should contact your doctor.

• If you are a cancer patient you should be aware that Aranesp may act as a blood cell growth factor and in some circumstances may have a negative impact on your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.
• Misuse by healthy people can cause life-threatening problems with the heart or blood vessels.

Using other medicines

Cyclosporin and tacrolimus (medicines which suppress the immune system) may be affected by the number of red cells in your blood. It is important to tell your doctor if you are taking either of these medicines.

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Using Aranesp with food and drink

Food and drink do not affect Aranesp.

Pregnancy and breast-feeding

Aranesp has not been tested in pregnant women. It is important to tell your doctor if you:

• are pregnant;
• think you may be pregnant; or
• plan to get pregnant.

It is not known whether darbepoetin alfa is excreted in human milk. You must stop breast-feeding if you use Aranesp.

Driving and using machines

Aranesp should not affect your ability to drive or use machinery.

Important information about some of the ingredients of Aranesp

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium- free?.

Following blood tests, your doctor has decided you need Aranesp as your haemoglobin level is 10 g/dl or less. Your doctor will tell you how much and how often you must take Aranesp 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.

Injecting Aranesp yourself

Your doctor may decide that it is best for you or a carer to inject Aranesp. Your doctor, nurse or pharmacist will show you how to inject yourself with the pre-filled syringe. Do not try to inject yourself if you have not been trained. Never inject Aranesp into a vein yourself.

If you have chronic renal failure

Aranesp is given as a single injection, either once a week, once every two weeks, or once every month either under your skin (subcutaneous) or into a vein (intravenous).

In order to correct your anaemia, your initial dose of Aranesp per kilogram of your body weight will be either:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once weekly Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose once every four weeks as necessary.

Once your anaemia is corrected, your doctor will continue to regularly check your blood and your dose may be adjusted further in order to maintain long-term control of your anaemia. Your doctor will inform you if your dose changes.

Your blood pressure will also be checked regularly, particularly at the beginning of your treatment.

In some cases, your doctor may recommend that you take iron supplements.

Your doctor may decide to change the way that your injection is given (either under the skin or into a vein). If this changes you will start on the same dose as you have been receiving and your doctor will take blood samples to make sure that your anaemia is still being managed correctly.

If your doctor has decided to change your treatment from r-HuEPO (erythropoietin produced by gene-technology) to Aranesp, they will choose whether you should receive your Aranesp injection once weekly or once every two weeks. The route of injection is the same as with r-HuEPO but your doctor will tell you how much you should take, and when, and may adjust your dose if necessary.

If you are receiving chemotherapy

Aranesp is given as a single injection, either once a week or once every three weeks, under your skin.

In order to correct your anaemia, your initial dose will be

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of your body weight), or
• 2.25 micrograms (once weekly) of Aranesp per kilogram of your body weight. Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose as necessary. Your treatment will continue until approximately four weeks after the end of your chemotherapy. Your doctor will tell 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 could have serious problems if you take more Aranesp than you need. You should contact your doctor, nurse or pharmacist if this does happen. If you feel unwell in any way you should contact your doctor, nurse or pharmacist immediately.

If you forget to inject Aranesp

If you have forgotten a dose of Aranesp, you should contact your doctor to discuss when you should inject the next dose.

Like all medicines, Aranesp may cause side effects, although not everybody gets them.

The following side effects have been experienced by some patients in clinical trials taking Aranesp:

Chronic renal failure patients

Very Common (seen in more than 10 in 100 people)

• High blood pressure (hypertension)

Common (seen in more than 1 in 100 people)

• Pain around the area injected
• Rash and/or redness of the skin

Rare (seen in more than 1 in 10,000 people)

• Blood clots (thrombosis)

Cancer patients

Very common (seen in more than 10 in 100 people)

• Fluid retention (oedema)

Common (seen in more than 1 in 100 people)

• Blood clots (thrombosis)
• Pain around the area injected
• Rash and/or redness of the skin

The following side effects have been experienced by some patients after Aranesp has been marketed:

Very rare (seen in less than 1 in 10,000 people)

• Pure red cell aplasia (PRCA) ? (anaemia, unusual tiredness, lack of energy)

Frequency unknown

• Serious allergic reactions which may include:
• Sudden life-threatening allergic reactions (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rash
• Hives (urticaria)
• Convulsions (fits and seizures) have been reported in patients treated with Aranesp
• Hypertension

If you have any of these symptoms or you notice any side effects that are not mentioned in this leaflet, please tell your doctor, nurse or pharmacist.

Keep out of the reach and sight of children.

Do not use Aranesp after the expiry date which is stated on the carton and on the pre-filled syringe label 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 carton in order to protect from light.

When your syringe has been removed from the refrigerator and left at room temperature for approximately 30 minutes before injection it must either be used within 7 days or disposed of.

Do not use Aranesp if you notice the pre?filled syringe contents are cloudy or there are particles in it.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Aranesp contains

• The active substance is darbepoetin alfa.The pre-filled syringe contains either 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300 or 500 micrograms of darbepoetin alfa.
• The other ingredients are sodium phosphate monobasic, sodium phosphate dibasic, sodium chloride, polysorbate 80 and water for injections.

What Aranesp looks like and contents of the pack

Aranesp is a clear, colourless or slightly pearly solution for injection in a pre-filled syringe.

Aranesp is available in packs of 1 or 4 pre-filled syringes with automatic needle guard in a blister wrapping. Not all pack sizes may be marketed.

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

Further information

If you want more information about this medicine, please contact the local representative of the company that is authorised to market Aranesp.

BelgiëBelgiqueBelgien s.a. Amgen n.v. TelTél 32 02 7752711 LuxembourgLuxemburg s.a. Amgen BelgiqueBelgien TelTél 32 02 7752711

359 02 805 7020 Magyarország Amgen Kft. Tel. 36 1 35 44 700

eská republika Amgen s.r.o. Tel 420 2 21 773 500 Malta Amgen B.V. The Netherlands Tel 31 076 5732500

Danmark Amgen filial af Amgen AB, Sverige Tlf 45 39617500 Nederland Amgen B.V. Tel 31 076 5732500

Deutschland AMGEN GmbH Tel. 49 089 1490960 Norge Amgen AB Tel 47 23308000

Eesti Amgen Switzerland AG Eesti filiaal Tel 372 512 5501 Österreich Amgen GmbH Tel 43 01 50 217

Genesis Pharma S.A. 30 210 8771500 Polska Amgen Sp. z o.o. Tel. 48 22 581 3000

España Amgen S.A. Tel 34 93 600 19 00 Portugal AMGEN Biofarmacêutica, Lda. Tel 351 21 4220550

France Amgen S.A.S. Tél 33 01 40 88 27 00 România Amgen România SRL Tel. 4021 527 30 00

Slovenija AMGEN zdravila d.o.o. Tel 386 1 585 1767 Ireland Amgen Limited United Kingdom Tel 44 01223 420305

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika Amgen Switzerland AG, Slovakia Tel 421 33 321 13 22

Italia Amgen Dompé S.p.A. Tel 39 02 6241121 SuomiFinland Amgen AB, sivuliike SuomessaAmgen AB, filial i Finland PuhTel 358 09 54900500

K Genesis Pharma Cyprus Ltd 357 22 76 99 46 Sverige Amgen AB Tel 46 08 6951100

Latvija Amgen Switzerland AG Rgas filile Tel 371 29284 807 United Kingdom Amgen Limited Tel 44 01223 420305

Lietuva

Amgen Switzerland AG Vilniaus filialas
Tel: +370 6983 6600

This leaflet was last approved in

INSTRUCTIONS FOR INJECTING WITH THE ARANESP PRE-FILLED SYRINGE

This section contains information on how you, or the person injecting you, use the Aranesp pre-filled syringe. It is important that you do not try to give yourself the injection unless you have received training from your doctor, nurse or pharmacist. If you have questions about how to inject, please ask your doctor, nurse or pharmacist for assistance.

Before you begin

Read all instructions thoroughly before using the pre-filled syringe.

To reduce the risk of accidental needle sticks to users, each pre-filled syringe is equipped with a needle guard that is automatically activated to cover the needle after complete delivery of the pre-filled syringe content.

DO NOT attempt to activate the needle guard prior to injection.

The pre-filled syringe barrel has a detachable label that can be pulled off after injection. The label is used by healthcare professionals to update a patient?s chart.

DO NOT use the pre-filled syringe if the needle cover has been removed, or the needle guard has been activated (covering the needle).

DO NOT try to remove the detachable label on the pre-filled syringe barrel before administering the injection.

How do I use the Aranesp pre-filled syringe?

Your doctor has prescribed an Aranesp pre-filled syringe for injection into the tissue just under the skin. Your doctor, nurse, or pharmacist will tell you how much Aranesp you need and how frequently it should be injected.

Equipment:

To give yourself an injection you will need:

• a new Aranesp pre-filled syringe; and
• alcohol wipes or similar.

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

1. Remove the pre-filled syringe from the refrigerator. Do not pick up the pre-filled syringe by the plunger or needle cover. This could damage the device.

2. Leave the pre-filled syringe at room temperature for approximately 30 minutes. This will make the injection more comfortable. Do not warm Aranesp in any other way (for example, in a microwave or in hot water). Do not leave the syringe exposed to direct sunlight.

3. Do not shake the pre-filled syringe.

4. Do not remove the cover from the pre-filled syringe until you are ready to inject.

5. Check that it is the correct dose that your doctor has prescribed.

6. Check the expiry date on the pre-filled syringe label (EXP:). Do not use it if the date has passed the last day of the month shown.

7. Check the appearance of Aranesp. It must be a clear, colourless or slightly pearly liquid. If it is cloudy or there are particles in it, you must not use it.

8. Wash your hands thoroughly.

9. Find a comfortable, well-lit, clean surface and put all the equipment you need within reach.

Where should I give my injection The best places to inject yourself are the top of your thighs and the abdomen. If someone else is injecting for you, they can also use the back of your arms. Change the injection site if you notice the area is red or sore.

How do I give my injection 1. Disinfect your skin by using an alcohol wipe. 2. To avoid bending the needle, gently pull the cover from the needle straight off without twisting as shown. Do not touch the needle or push the plunger. 3. You may notice a small air bubble in the pre-filled syringe. You do not have to remove the air bubble before injecting. Injecting the solution with the air bubble is harmless.

4. Pinch (without squeezing) the skin between your thumb and forefinger. Put the needle fully into the skin as shown by your nurse or doctor.

5. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, pull the needle out and re-insert it in another place after disinfecting the skin.

6. Push the plunger with a slow constant pressure, always keeping your skin pinched.

Push the plunger all the way down as far as it will go to inject all the liquid. The needle guard will not activate unless you empty the pre-filled syringe.

7. While the plunger is still pressed all the way down, remove the needle from the skin, then release the plunger and allow the syringe to move up until the entire needle is covered by the needle guard. If the needle guard is not activated, an incomplete injection may have occurred. Call your health care provider if you think you have not received the full dose. DO NOT put the needle cover back on the needle.

8. If you notice a spot of blood you may gently dab it away with a cotton ball or tissue. Do not rub the injection site.If needed, you may cover the injection site with a plaster.

9. Only use each pre-filled syringe for one injection. Do not use any Aranesp that is left in the syringe.

Remember: If you have any problems, please ask your doctor or nurse for help and advice.

Disposing of used syringes

• DO NOT put the needle cover back on used syringes.
• Keep used syringes out of the reach and sight of children.
• The used syringe should be disposed of in accordance with local requirements. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.--------------------------------------------------------------------------------------------------------------------------- The following information is intended for medical or healthcare professionals only:

How to remove the detachable label

The Aranesp pre-filled syringe comes with a detachable label that can be removed and placed on a patient?s chart.

NOTE: Only perform this step after you have given the injection and the safety guard is covering the needle.

1. Hold the syringe as shown and rotate the plunger towards you until you can see the tab of

the label within the opening of the window as shown below.

2. Slightly rotate the plunger away from you until the tab sticks up through the window as shown below.

3. Pull the tab up through the window, and then tear across the perforation, as shown below.

Tear at perforation