Label: information for the user

Aranesp 10 micrograms injectable solution in pre-filled syringe

Aranesp 15 micrograms injectable solution in pre-filled syringe

Aranesp 20 micrograms injectable solution in pre-filled syringe

Aranesp 30 micrograms injectable solution in pre-filled syringe

Aranesp 40 micrograms injectable solution in pre-filled syringe

Aranesp 50 micrograms injectable solution in pre-filled syringe

Aranesp 60 micrograms injectable solution in pre-filled syringe

Aranesp 80 micrograms injectable solution in pre-filled syringe

Aranesp 100 micrograms injectable solution in pre-filled syringe

Aranesp 130 micrograms injectable solution in pre-filled syringe

Aranesp 150 micrograms injectable solution in pre-filled syringe

Aranesp 300 micrograms injectable solution in pre-filled syringe

Aranesp 500 micrograms injectable solution in pre-filled syringe

darbepoetina alfa (darbepoetin alfa)

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

Your doctor has prescribed Aranesp (an erythropoiesis-stimulating agent) for the treatment of your anemia. Anemia occurs when the blood does not contain enough red blood cells, and symptoms can include fatigue, weakness, and shortness of breath.

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

If you have chronic kidney disease

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

As your body will need some time to produce more red blood cells, it may take about four weeks before you notice any effect. Your normal 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 treated with chemotherapy.

One of the main side effects of chemotherapy is that it causes the bone marrow to stop producing enough red blood cells. Towards the end of chemotherapy treatment, especially if you have received a lot of chemotherapy, the red blood cell count may decrease, causing anemia.

No use Aranesp:

• If you are allergic to darbepoetin alfa or any of the other components of this medication (listed in section 6).
• If you have high blood pressure that is not being treated with other prescription medications by your doctor.

Advertencias and precautions

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

Inform your doctor if youhaveorhave had:

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

Special precautions:

• If you experience symptoms such as excessive fatigue and lack of energy, it may be due to a condition called pure red cell aplasia (PRCA) that has been observed in some patients. PRCA means that the body has reduced or stopped the production of 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.

• Be cautious with other medications that stimulate red blood cell production: Aranesp belongs to a group of medications that stimulate red blood cell production, just like human erythropoietic proteins. Your doctor should always keep a record of the exact medication you are using.

• If you are a patient with chronic renal insufficiency and especially if you do not respond correctly to Aranesp, your doctor will review the Aranesp dose, as repeated increases in the Aranesp dose may increase the risk of cardiovascular problems and may increase the risk of myocardial infarction, stroke, and death.

• Your doctor will try to maintain your hemoglobin levels between 10 and 12 g/dl. Your doctor will check that your hemoglobin does not exceed a certain level, as high hemoglobin concentrations may put you at risk of cardiovascular problems and may increase the risk of myocardial infarction, stroke, and death.

• If you experience symptoms that include severe headache, numbness, confusion, vision problems, nausea, vomiting, or seizures (convulsions), it may mean that you have very high blood pressure. If you experience these symptoms, you should contact your doctor.

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

• The use of this medication in healthy individuals may cause cardiovascular problems that can be fatal.

• Cases of severe skin reactions associated with epoetin treatment, including Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (TEN), have been reported. SSJ/TEN may initially appear as red spots similar to a bull's-eye or circular spots frequently with central blisters on the torso. Additionally, ulcers may occur in the mouth, throat, nose, genitals, and eyes (red and swollen eyes). These severe eruptions are often preceded by fever and/or flu-like symptoms. The eruptions may progress to widespread skin peeling and potentially fatal complications.

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

Use of Aranesp with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Ciclosporin and tacrolimus (immunosuppressive medications) may be affected by red blood cell count. It is essential to inform your doctor if you are using any of these medications.

Use of Aranesp with food and beverages

Food and beverages do not affect Aranesp.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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

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

The elimination of darbepoetin alfa by breast milk is unknown. If you are being treated with Aranesp, you should stop breastfeeding.

Driving and operating machinery

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

Aranesp contains sodium

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

After blood tests, your doctor has decided that you need Aranesp since 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 maintain your hemoglobin level between 10 and 12 g/dl. This may vary depending on whether you are an adult or a child.

How to inject Aranesp yourself

Your doctor may decide that it is better for you or the people who care for you to inject Aranesp. Your doctor, nurse, or pharmacist will teach you how to put the injection with the preloaded syringe. Do not attempt to self-inject if you have not been taught how to do it.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 in a single injection, either subcutaneously or intravenously.

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

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

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

For all adult and pediatric patients ≥ 1 year of age with chronic renal failure, once anemia is corrected, Aranesp will continue to be administered in a single injection, either once a week or 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 take regular blood tests to see how you are responding to anemia treatment and, if necessary, may adjust the dose every four weeks to maintain long-term control of your anemia.

Your doctor will use the most 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 you need to change your Aranesp doses.

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

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

Your doctor may decide to change the way you receive the injection (subcutaneously or intravenously). If this occurs, you will start with the same dose you were receiving before and blood tests will be done to check that anemia is being treated correctly.

If your doctor has decided to change your r-HuEPO (genetically engineered erythropoietin) treatment to Aranesp, they will choose between administering Aranesp once a week or every two weeks. The administration route will be the same as with r-HuEPO, but your doctor will decide how much and when to administer it, and may adjust the dose you receive if necessary.

If you are receiving chemotherapy

Aranesp is administered subcutaneously in a single injection, once a week or every three weeks.

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

• 500 micrograms 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 take regular blood tests to measure how you are responding to anemia, 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 have 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 do not feel well, contact your doctor or pharmacist immediately.

If you forgot to use Aranesp

Do not take a double dose to compensate for the missed doses.

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

If you interrupt Aranesp treatment

If you want to stop using Aranesp, you must first discuss it with your doctor.

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

Some patients have experienced the following side effects while using Aranesp:

Patients with chronic renal insufficiency

Very common:may affect more than 1 in 10 people

Common:may affect up to 1 in 10 people

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

Uncommon:may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Convulsions (seizures and attacks)

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

• Pure red cell aplasia (PRCA) – (anemia, excessive fatigue, lack of energy)

Patients with cancer

Very common:may affect more than 1 in 10 people

• Allergic reactions
• Fluid retention (edema)

Common:may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain at the injection site
• Rash and/or redness of the skin

Uncommon:may affect up to 1 in 100 people

• Convulsions (seizures and attacks)

All patients

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

• Severe allergic reactions that may include:
• Unexpected allergic reactions that may put your life at risk (anaphylaxis)
• Swelling of the face, lips, mouth, tongue, or throat that may cause difficulty swallowing or breathing (angioedema)
• Difficulty breathing (allergic bronchospasm)
• Rashes on the skin
• Hives (urticaria)
• Severe skin eruptions, including Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (TEN), have been reported associated with epoetin treatment. These may appear as red spots similar to a bullseye or circular patches frequently with central blisters on the torso, skin peeling, mouth, throat, nose, genitals, and eyes and may be preceded by fever or flu-like symptoms. These severe eruptions are often preceded by fever or flu-like symptoms.

Stop taking Aranesp if you experience these symptoms and inform your doctor or seek medical attention immediately. See section 2.

• Haematomas and bleeding at the injection site

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the label after “CAD” or “EXP”. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze. Do not use Aranesp if you believe it has been frozen.

Store the pre-filled syringe in the outer packaging to protect it from light.

Once you have removed your pre-filled syringe from the refrigerator and allowed it to reach room temperature for approximately 30 minutes before injecting it, you must use it within the next 7 days or discard it.

Do not use this medication if you observe that the content of the pre-filled syringe is cloudy or contains particles.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Aranesp

• The active ingredient is darbepoetin alfa, r-HuEPO (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 sodium monobasic phosphate, sodium dibasic phosphate, sodium chloride, polisorbate 80 and water for injection.

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 of 1 or 4 pre-filled syringes. The syringes are supplied in a blister pack (packs with 1 and 4 syringes) or without a blister pack (packs with 1 syringe). Only some pack sizes may be marketed.

Holder of the marketing authorisation and manufacturer responsible

Amgen Europe B.V.

Minervum 7061

NL-4817 ZK Breda

Netherlands

Holder of the marketing authorisation

Amgen Europe B.V.

Minervum 7061

NL-4817 ZK Breda

Netherlands

Manufacturer

Amgen Technology (Ireland) Unlimited Company

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medicinal product by contacting the local representative of the holder of the marketing authorisation.

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu.

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

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

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

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

Material:

To administer the injection, you will need:

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

What should you do before administering the subcutaneous injection of Aranesp?

1. Remove the pre-filled syringe from the refrigerator. Leave the pre-filled syringe at room temperature for approximately 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 pre-filled syringe to direct sunlight.

1. Do not shake the pre-filled syringe.

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

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

1. Check the expiration date indicated on the label of the pre-filled syringe (EXP). Do not use it if the current date has exceeded the last day of the month indicated.

1. Check the appearance of Aranesp. It should be a transparent, colourless or slightly opalescent liquid. If it is cloudy or contains particles, do not use it.

1. Wash your hands thoroughly.

1. Find a comfortable, clean and well-lit surface and place all the material you need within reach.

How to prepare the Aranesp injection?

Before injecting Aranesp, you must do the following:

Where should you administer the injection?

How to administer the injection?

1. Disinfect the skin using an alcohol swab and pinch it (without squeezing) between your thumb and index finger.

1. Insert the needle completely into the skin as instructed by your doctor, nurse or pharmacist.

1. Inject the prescribed dose subcutaneously as instructed by your doctor, nurse or pharmacist.

1. Push the plunger slowly and steadily, keeping the skin pinched at all times until the syringe is empty.

1. Remove the needle and release the skin.

1. If you notice any remaining blood, you can remove it gently with a little alcohol swab or gauze. Do not rub the injection site. If necessary, you can cover the injection site with a bandage.

1. Use each syringe for a single injection. Do not use the remaining Aranesp that may be left in the syringe.

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

How to dispose of used syringes?

• Do not put the needle cap back on the used needles, as you may accidentally prick yourself.
• Keep the used syringes out of reach and sight of children.
• The pre-filled syringes must be disposed of in accordance with local requirements. Ask your pharmacist how to dispose of unused medicines. This will help protect the environment.