Aranesp 80 micrograms solution for injection in a pre-filledpen

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 pen 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 injection is to be given under the skin (subcutaneous), and so you may use the Aranesp pre-filled pen. 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 has decided that the Aranesp pre-filled pen is the best way for you, a nurse, or a carer to inject Aranesp. Your doctor, nurse or pharmacist will show you how to inject yourself with the pre-filled pen. Do not try to inject yourself if you have not been trained. Never inject Aranesp into a vein yourself. The pre-filled pen is designed to inject the area under your skin only.

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

If you have chronic renal failure

The Aranesp pre-filled pen is given as a single injection, either once a week, once every two weeks, or once every month.

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 pen 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 pen in the outer carton in order to protect from light.

When your pen 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 pen 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 pen 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 pen.

Aranesp (SureClick) is available in packs containing 1 or 4 pre-filled pens. 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 PEN

(SURECLICK)

This section contains information on how to properly use the Aranesp pre-filled pen. It is importantthat 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.

How do you, or the person injecting you, use Aranesp pre-filled pen (SureClick)?

Your doctor has prescribed the Aranesp pre-filled pen 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. Only use each pre-filled pen for one injection.

Equipment:

To give yourself an injection you will need:

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

Preparing for an Aranesp injection?

1. Remove the pen from the refrigerator. For a more comfortable injection, leave the pen at room temperature for approximately 30 minutes. Do not warm Aranesp in any other way (for example, do not warm it in a microwave or in hot water). Additionally, do not leave the pre-filled pen exposed to direct sunlight.

2. Do not shake the pre-filled pen.

3. Do not remove the grey needle cap from the pre-filled pen until you are ready to inject.

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

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

6. Check the appearance of Aranesp through the inspection window. 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.

7. Wash your hands thoroughly.

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

Grey needle cap Red button Inspection window

7a. Choosing and preparing an injection site

1. Choose an injection site

The injection site must be firm for the device to work properly.

The preferred injection site for using the Aranesp pre-filled pen is the front of the thigh.

Rotate injection site:
You may rotate the site for each injection to avoid soreness at any one site.

Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks.

2a. Instructions for preferred injection site

The front of the thigh is the preferred injection site.

2b. Instructions for alternate injection sites

When using alternate injection sites, it is particularly important to create enough surface tension on the site to be able to successfully complete the injection.

Stretch technique Stretch Make sure that skin under and around the pre-filled pen is firm and tight to provide enough resistance to fully retract the safety guard and unlock the pen.

You can use the abdomen, except for the 2 inch5 cm area around the belly button navel. For the abdomen, it is recommended to lie down on your back, and stretch the skin at the injection site to create a firm and tight surface.

If someone else is giving you the injection, they can also use the outer area of the upper arms. For the upper arms, it is recommended to stretch the skin at the injection site to create a firm and tight surface

3. Prepare the site

To prepare the area of skin where Aranesp will be injected, wipe the injection site with an alcohol wipe. Do not touch this area again before giving the injection.

7b. Injecting Aranesp using the pre-filled pen

1. Pull off the grey needle cap.

Pull off the grey needle cap Do not twist the grey needle cap Do not try to put the needle cap back onto the pre-filled pen Do pull the grey cap straight off Safety guard

2. Do not touch the red button. Press the pre-filled pen onto the skin to unlock the safety guard.

Locked with safety guard
out

Unlocked with safety
guard fully retracted

Do not press the red button until the safety guard is fully retracted.

Do keep enough downward pressure to fully retract the yellow safety guard and to keep the red button unlocked. Do hold the pre-filled pen at a right angle 90 to the injection site.

3. Briefly press and release red button.

Release button

CLIC

- Do maintain pressure on the skin during the injection

4. Count slowly to 15 seconds for injection to end.

Medicine will be automatically injected

Do not move the pre-filled pen during the injection.

Do wait for the injection to finish before releasing pressure. You may hear a second click as the red button pops back up.

5. Check window to confirm delivery of full dose

Do check the inspection window to confirm it has turned yellow. If the inspection window is not yellow, you must contact your doctor, nurse or pharmacist. Safety guard down after use.

There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site

Do not rub the injection site.If needed, you may cover the injection site with a plaster.

Remember

If you have any problems, please do not be afraid to ask your doctor or nurse for help and advice.

Disposing of used pre-filled pens

• The Aranesp pre-filled pen should NEVER be reused.
• NEVER put the grey needle cap back into the used pre-filled pen.
• The used pre-filled pen 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.

Optional separate additional insert:

FRONT- Aranesp getting started guide:

Aranesp SureClick Pre-filled pen - Read package leaflet before use ENPreferred site is front of the thigh Turn over for injection steps Alternate sites are the abdomen or outer area of upper arms Stretch the skin on alternate injection sites GLISHStretch Injection site must be firm and tight

BACK- Aranesp getting started guide:

1 Pull off grey needle cap 5 Check window EN3 Briefly press and release red button. 4 Count slowly to 15 for injection to end. GLISH 2 Do not touch red button. Press the pen onto the skin to unlock safety guard. X Locked Click Complete when yellow Do not twist the grey needle cap Unlocked Keep unlocked against skin