Aranesp 10 micrograms solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Aranesp 10 micrograms solution for injection in pre-filled syringe

Aranesp 15 micrograms solution for injection in pre-filled syringe

Aranesp 20 micrograms solution for injection in pre-filled syringe

Aranesp 30 micrograms solution for injection in pre-filled syringe

Aranesp 40 micrograms solution for injection in pre-filled syringe

Aranesp 50 micrograms solution for injection in pre-filled syringe

Aranesp 60 micrograms solution for injection in pre-filled syringe

Aranesp 80 micrograms solution for injection in pre-filled syringe

Aranesp 100 micrograms solution for injection in pre-filled syringe

Aranesp 130 micrograms solution for injection in pre-filled syringe

Aranesp 150 micrograms solution for injection in pre-filled syringe

Aranesp 300 micrograms solution for injection in pre-filled syringe

Aranesp 500 micrograms solution for injection in pre-filled syringe

darbepoetin alfa (darbepoetin alfa)

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet as 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 and must not be given to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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
7. Instructions for self-injecting Aranesp from a pre-filled syringe

1. What Aranesp is and what it is used for

Your doctor has prescribed Aranesp (an antianaemic agent) to treat your anemia. Anemia occurs when the blood does not contain enough red blood cells, and symptoms may include fatigue, weakness, and shortness of breath.

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

If you have chronic renal failure

Aranesp is used to treat symptomatic anemia associated with chronic renal failure (kidney failure) in adults and children. In renal failure, the kidneys do not produce enough of the natural hormone erythropoietin, which often leads to anemia.

Since your body will need some time to produce more red blood cells, it will take about four weeks before you notice any effect. Your regular dialysis routine will not affect Aranesp's ability to treat anemia.

If you are receiving chemotherapy

Aranesp is used to treat symptomatic anemia in adult patients with non-myeloid tumors who are undergoing chemotherapy.

One of the main side effects of chemotherapy is that it causes the bone marrow to stop producing enough red blood cells. Toward the end of chemotherapy treatment, especially if you have received intensive chemotherapy, your red blood cell count may drop, leading to anemia.

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 high blood pressure that is not being treated with other medicines prescribed by your doctor.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Aranesp.

Tell your doctor if you have or have had:

• high blood pressure being treated with medicines prescribed by your doctor;
• sickle cell anemia;
• epileptic seizures (fits);
• convulsions (spasms and seizures);
• liver disease;
• do not respond to medications used to treat anemia;
• latex allergy (the needle cap of the pre-filled syringe contains a latex derivative);
• or hepatitis C.

Special precautions:

• If you experience symptoms such as unusual tiredness and lack of energy, this may be due to a condition called pure red cell aplasia (PRCA), which has been observed in some patients. PRCA means that your body has reduced or stopped producing red blood cells, leading to severe anemia. If you experience these symptoms, contact your doctor, who will determine the best way to treat your anemia.

• Exercise special caution with other medicines that stimulate red blood cell production: Aranesp belongs to a group of medicines that stimulate the production of red blood cells in the blood, similar to human erythropoietic proteins. Your doctor should always keep a record of the exact medicine you are using.

• If you are a patient with chronic renal failure and especially if you do not respond adequately to Aranesp, your doctor will review the Aranesp dose, because if you do not respond to treatment, repeated dose increases of Aranesp may increase the risk of heart or blood vessel problems and could increase the risk of myocardial infarction, stroke, and death.

• Your doctor will aim to keep your hemoglobin levels between 10 and 12 g/dL. Your doctor will monitor to ensure your hemoglobin does not exceed a certain level, as high hemoglobin concentrations may put you at risk of heart or blood vessel problems and could increase the risk of myocardial infarction, stroke, and death.

• If you experience symptoms such as severe headache, numbness, confusion, vision problems, nausea, vomiting, or seizures (convulsions), this could mean you have very high blood pressure. If you experience these symptoms, contact your doctor immediately.

• If you are a cancer patient, you should know that Aranesp can act as a growth factor for blood cells and, under certain circumstances, may have a negative effect on your cancer. Depending on your individual situation, a blood transfusion may be preferable. Please discuss this with your doctor.

• Use of this medicine in healthy individuals may cause heart or blood vessel problems that could be fatal.

• Serious skin reactions have been reported with epoetin therapy, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS/TEN may initially appear as red, target-like spots or circular rashes, often with central blisters, typically on the trunk. In addition, ulcers may develop in the mouth, throat, nose, genitals, and eyes (red, swollen eyes). These serious rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread skin peeling and potentially life-threatening complications.

If you develop a severe rash or any of these skin symptoms, stop taking Aranesp and inform your doctor or seek immediate medical attention.

Using Aranesp with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Cyclosporine and tacrolimus (medicines that suppress the immune system) may be affected by changes in red blood cell count. It is important to inform your doctor if you are taking any of these medicines.

Using Aranesp with food and drink

Food and drink do not affect Aranesp.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

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

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

It is unknown whether darbepoetin alfa is excreted in breast milk. If you are being treated with Aranesp, you should discontinue breastfeeding.

Driving and using machines

Aranesp should not affect your ability to drive or operate machinery. 211

Aranesp contains sodium

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

3. How to use Aranesp

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

After blood tests, your doctor has decided that you need Aranesp because your hemoglobin level is equal to or less than 10 g/dl. Your doctor will tell you how much Aranesp you need and how often you should use it to keep your hemoglobin level between 10 and 12 g/dl. This may vary depending on whether you are an adult or a child.

How to self-inject Aranesp

Your doctor may decide it is best for you or for caregivers to inject Aranesp yourself. Your doctor, nurse, or pharmacist will teach you how to give the injection using the pre-filled syringe. Do not attempt to self-inject if you have not been trained. Never inject Aranesp yourself into a vein.

If you have chronic renal failure

For all adult and pediatric patients ≥ 1 year of age with chronic renal failure, Aranesp is administered as a single injection under the skin (subcutaneously) or into a vein (intravenously).

To correct anemia, the initial dose of Aranesp per kilogram of body weight will be:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once a week.

For adult patients not undergoing dialysis, 1.5 micrograms/kg once a month may also be used as the initial dose.

For all adult and pediatric patients ≥ 1 year of age with chronic renal failure, once your anemia is corrected, you will continue receiving Aranesp as a single injection, either once a week or once every two weeks. For all adult and pediatric patients ≥ 11 years of age who are not on dialysis, Aranesp may also be administered as a monthly injection.

Your doctor will perform regular blood tests to monitor how your anemia is responding to treatment and, if necessary, may adjust your dose every four weeks to maintain long-term control of your anemia.

Your doctor will use the lowest effective dose to control your anemia symptoms.

If you do not respond adequately to Aranesp, your doctor will review your dose and inform you if a dose adjustment is needed.

Your doctor will measure your blood pressure regularly, especially at the beginning of treatment.

In some cases, your doctor may recommend that you take iron supplements. 212

Your doctor may decide to change the route of administration (under the skin or into the vein). If this occurs, you will start with the same dose you were previously receiving, and blood tests will be performed to ensure your anemia continues to be properly treated.

If your doctor has decided to switch your treatment from r-HuEPO (recombinant human erythropoietin) to Aranesp, they will choose between administering Aranesp once a week or once every two weeks. The route of administration will be the same as with r-HuEPO, but your doctor will determine the dose and timing, and may adjust your dose as necessary.

If you are receiving chemotherapy

Aranesp is administered under the skin as a single injection, once a week or once every three weeks.

To correct your anemia, the initial dose of Aranesp will be:

• 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight), or
• 2.25 micrograms of Aranesp per kilogram of body weight (once a week).

Your doctor will regularly take blood samples to monitor your response to treatment and may adjust the dose as needed. Treatment will continue until approximately 4 weeks after the end of 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 may experience serious problems if you administer more Aranesp than you should, such as very high blood pressure. Contact your doctor or pharmacist if this occurs. If you feel unwell, contact your doctor or pharmacist immediately.

If you forget to use Aranesp

Do not take a double dose to make up for missed doses.

If you forget to inject a dose of Aranesp, contact your doctor to determine when you should inject the next dose.

If you stop using Aranesp

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Some patients have experienced the following adverse effects when using Aranesp:

Patients with chronic renal failure

Very common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions 213

Common: may affect up to 1 in 10 people

• • Stroke
• Pain at the injection site
• Skin rash and/or redness

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Seizures (spasms and fits)

Frequency not known: frequency cannot be estimated from the available data

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

Patients with cancer

Very common: may affect more than 1 in 10 people

• Allergic reactions
• Fluid retention (oedema)

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Skin rash and/or redness

Uncommon: may affect up to 1 in 100 people

• Seizures (spasms and fits)

All patients

Frequency not known: frequency cannot be estimated from the available data

• Severe allergic reactions which may include:
• Unexpected allergic reactions that may be life-threatening (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat that may cause difficulty swallowing or breathing (angioedema)
• Difficulty breathing (allergic bronchospasm)
• Skin rashes
• Rash (urticaria)
• Severe skin rashes, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with epoetin therapy. These may appear as reddish macules resembling target lesions or circular spots, often with central blisters on the trunk, skin peeling, mouth ulcers, and sores in the throat, nose, genitals and eyes, and may be preceded by fever or flu-like symptoms. These severe rashes are often preceded by fever or flu-like symptoms.

Stop taking Aranesp if you experience any of these symptoms and contact your doctor or seek immediate medical attention. See also section 2.

• Bruising and bleeding at the injection site

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 after “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 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 it from light.

Once you have removed your syringe from the refrigerator and allowed it to reach room temperature for about 30 minutes before injecting, it must be used within the following 7 days or discarded.

Do not use this medicine if the solution in the pre-filled syringe appears cloudy or contains particles.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Aranesp

• The active substance is darbepoetin alfa, r-HuEPO (recombinant human erythropoietin produced by genetic technology). The pre-filled syringes contain 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.

Appearance of the product and contents of the pack

Aranesp is a transparent, colourless or slightly opalescent injectable solution in a pre-filled syringe.

Aranesp is available in packs containing 1 or 4 pre-filled syringes. The syringes are supplied in blisters (packs with 1 and 4 syringes) or without blister (packs with one syringe). Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Amgen Europe B.V.

Minervum 7061

NL-4817 ZK Breda

The Netherlands

Marketing Authorisation Holder

Amgen Europe B.V.

Minervum 7061

NL-4817 ZK Breda

The Netherlands

Manufacturer

Amgen Technology (Ireland) Unlimited Company

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

More information about this medicinal product is available upon request to the local representative of the Marketing Authorisation Holder.

Belgium/Belgium/Belgium s.a. Amgen n.v. Tel/Tel: +32 (0)2 7752711	Lithuania Amgen Switzerland AG Vilnius Branch Tel: +370 5 219 7474
	Luxembourg/Luxembourg s.a. Amgen Belgium/Belgium Tel/Tel: +32 (0)2 7752711
Czech Republic Amgen s.r.o. Tel: +420 221 773 500	Hungary Amgen Kft. Tel.: +36 1 35 44 700
Denmark Amgen, branch of Amgen AB, Sweden Tlf: +45 39617500	Malta Amgen B.V. The Netherlands Tel: +31 (0)76 5732500
Germany AMGEN GmbH Tel.: +49 89 1490960	Netherlands Amgen B.V. Tel: +31 (0)76 5732500
Estonia Amgen Switzerland AG Vilnius Branch Tel: +372 586 09553	Norway Amgen AB Tel: +47 23308000
Greece Amgen Hellas Pharmaceutical Co. Ltd. Tel.: +30 210 3447000	Austria Amgen GmbH Tel: +43 (0)1 50 217
Spain Amgen S.A. Tel: +34 93 600 18 60	Poland Amgen Biotechnologia Sp. z o.o. Tel.: +48 22 581 3000
France Amgen S.A.S. Tél: +33 (0)9 69 363 363	Portugal Amgen Biofarmacêutica, Lda. Tel: +351 21 4220550
Croatia Amgen d.o.o. Tel: +385 (0)1 562 57 20	Romania Amgen România SRL Tel: +4021 527 3000
Ireland Amgen Limited United Kingdom Tel: +44 (0)1223 420305	Slovenia AMGEN zdravila d.o.o. Tel: +386 (0)1 585 1767
Iceland Vistor hf. Tel: +354 535 7000	Slovakia Amgen Slovakia s.r.o. Tel: +421 2 321 114 49
Italy Amgen S.r.l. Tel: +39 02 6241121	Finland/Finland Amgen AB, branch in Finland/Amgen AB, filial i Finland Puh/Tel: +358 (0)9 54900500
Cyprus C.A. Papaellinas Ltd Tel.: +357 22741 741	Sweden Amgen AB Tel: +46 (0)8 6951100
Latvia Amgen Switzerland AG Riga Branch Tel: +371 257 25888	United Kingdom Amgen Limited Tel: +44 (0)1223 420305

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

1. Instructions for self-injecting Aranesp from a pre-filled syringe

This section contains information on how to self-inject Aranesp. It is important that you do not attempt to administer the injection yourself unless your doctor, nurse, or pharmacist has trained you to do so. If you have any doubts about how to give the injection, consult your doctor, nurse, or pharmacist.

How should you or the person administering the Aranesp injection use the pre-filled syringe?

Your doctor has prescribed Aranesp in a pre-filled syringe, and you must inject its contents into the tissue beneath the skin. Your doctor, nurse, or pharmacist will tell you the amount of Aranesp you need and how often you should receive it.

Materials:

To administer the injection, you will need:

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

What should you do before giving the subcutaneous Aranesp injection?

1. Remove the pre-filled syringe from the refrigerator. Allow the pre-filled syringe to reach room temperature for about 30 minutes. This will make the injection more comfortable. Do not heat Aranesp in any other way (for example, do not heat it in a microwave or in hot water). Do not expose the syringe to direct sunlight.

2. Do not shake the pre-filled syringe.

3. Do not remove the needle cap until you are ready to administer the injection.

4. Check that it is the dose prescribed by your doctor.

5. Check the expiry date shown on the label of the pre-filled syringe (EXP). Do not use it if the current date is past the last day of the month indicated.

6. Check the appearance of Aranesp. It should be a clear, colourless or slightly opalescent liquid. Do not use if it is cloudy or contains particles.

7. Wash your hands thoroughly.

8. Find a comfortable, clean, and well-lit surface and place all necessary materials within reach.

How to prepare the Aranesp injection?

Before injecting Aranesp, you must do the following:

To avoid bending the needle, gently pull off the needle cap without twisting, as shown in figures 1 and 2. Do not touch the needle or push the plunger. You may notice a small air bubble in the pre-filled syringe. Do not remove the air bubble before injection. Injecting the solution with an air bubble is not harmful. The pre-filled syringe is now ready for use.

Where should the injection be given?

The best places to self-administer the injection are the upper thighs and the abdomen. If someone else is administering the injection, it can also be given in the back of the upper arms. If you notice redness or swelling at the injection site, you may change the injection location.

How to administer the injection?

1. Disinfect the skin using a cotton ball with alcohol and pinch it (without squeezing) between the thumb and index finger.

2. Insert the needle completely into the skin as instructed 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 throughout until the syringe is empty.

5. Remove the needle and release the skin.

6. If you notice any blood remaining, gently wipe it away with a cotton ball or gauze. Do not rub the injection site. If needed, you may cover the injection site with a small bandage.

7. Use each syringe for only one injection. Do not use any remaining Aranesp left in the syringe.

Remember: If you have any problems, do not hesitate to ask your doctor or nurse for help and advice.

How to dispose of used syringes?

• Do not recap used needles, as you might accidentally prick yourself.
• Keep used syringes out of the reach and sight of children.
• Prefilled syringes must be disposed of according to local requirements. Ask your pharmacist how to dispose of medicines you no longer need. This will help protect the environment.