Package Insert: Information for the User

Neulasta 6 mg Injectable Solution

pegfilgrastim

Read the entire package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may 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 package insert. See section 4.

Neulasta contains the active ingredient pegfilgrastim. Pegfilgrastim is a protein produced by biotechnology in the bacteriaE. coli. Pegfilgrastim belongs to a group of proteins called cytokines, and is very similar to a natural protein (granulocyte colony-stimulating factor) produced by our body.

Neulasta is used to reduce the duration of neutropenia (low white blood cell count) and the incidence of febrile neutropenia (low white blood cell count and fever) that may be caused by cytotoxic chemotherapy (medicines that destroy rapidly dividing cells). White blood cells are important cells that contribute to fighting infections. These cells are sensitive to the effects of chemotherapy, which can cause their number to decrease. If the white blood cell count drops too low, there may not be enough to fight off bacteria, which implies a higher risk of contracting an infection.

Your doctor has prescribed Neulasta to stimulate your bone marrow (the part of the bone where blood cells are produced) to produce more white blood cells that will help you fight off infections.

No use Neulasta

• If you are allergic to pegfilgrastim, filgrastim, or any of the other components of this medication

Warnings and Precautions

Consult your doctor, pharmacist, or nurse before starting to use Neulasta:

• If you experience an allergic reaction that includes weakness, decreased blood pressure, difficulty breathing, facial swelling (anaphylaxis), redness and flushing, skin rash, and itching in areas of the skin.
• If you have a latex allergy. The cap of the pre-filled syringe contains a latex derivative that may cause severe allergic reactions.
• If you have an acrylic adhesive allergy. The body injector uses an acrylic adhesive that may cause allergic reactions.
• If you experience cough, fever, and difficulty breathing. This may be a sign of Acute Respiratory Distress Syndrome (ARDS).
• If you experience any or a combination of the following adverse effects:

Swelling that may be associated with urinating less frequently, difficulty breathing, swelling, and a feeling of abdominal fullness and a general feeling of fatigue.

These may be symptoms of a disease called "Capillary Leak Syndrome" and may cause blood to leak from a small blood vessel into other parts of your body. See section 4.

• If you have pain in the upper left abdominal area or pain in the shoulder tip. This may be a sign of a spleen problem (splenomegaly).
• If you recently had a severe lung infection (pneumonia), fluid in the lungs (pulmonary edema), inflammation of the lungs (interstitial lung disease), or an abnormal chest X-ray result (pulmonary infiltration).
• If you are aware of any alteration in blood cell count (e.g., increased number of white blood cells or anemia) or a decrease in platelet count, which may reduce the blood's ability to clot (thrombocytopenia). Your doctor may want to monitor you more closely.
• If you have sickle cell anemia. Your doctor may closely monitor your disease.
• If you are a breast cancer or lung cancer patient, the combined treatment of Neulasta with chemotherapy and/or radiation therapy may increase the risk of developing a pre-cancerous hematological disease called myelodysplastic syndrome (MDS) or a hematological neoplasm called acute myeloid leukemia (AML). Symptoms may include fatigue, fever, easy bruising, or bleeding.
• If you experience sudden signs of allergy, such as skin rash, itching, or urticaria, facial swelling, lips, tongue, or other body parts, shortness of breath, wheezing, or difficulty breathing, which may be signs of a severe allergic reaction.
• If you experience symptoms of aorta inflammation (the large blood vessel that carries blood from the heart to the rest of the body), which rarely has been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general discomfort, back pain, and increased inflammatory markers. Inform your doctor if you experience these symptoms.

Your doctor will perform regular blood and urine tests since Neulasta may damage the small filters within the kidneys (glomerulonephritis).

Severe skin reactions (Stevens-Johnson syndrome) have been reported with the use of Neulasta. Stop using Neulasta and seek medical attention immediately if you observe any of the symptoms described in section 4.

You should consult with your doctor about the risk of developing blood cancer. If you develop or may develop blood cancer, do not use Neulasta, except if your doctor advises you to.

Loss of response to pegfilgrastim

If you experience a loss of response or if you are unable to maintain the response to treatment with pegfilgrastim, your doctor will investigate the causes, including whether you have developed antibodies that may neutralize the activity of pegfilgrastim.

Other medications and Neulasta

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

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication. Neulasta has not been used in pregnant women. It is essential to inform your doctor if:

• You are pregnant;
• You think you may be pregnant; or
• You are planning to have a baby.

Unless your doctor advises you otherwise, you should stop breastfeeding if you use Neulasta.

Driving and operating machinery

The influence of Neulasta on the ability to drive and operate machinery is negligible or insignificant.

Neulasta contains sorbitol (E420) and sodium

This medication contains 30 mg of sorbitol in each pre-filled syringe equivalent to 50 mg/ml. This medication contains less than 1 mmol of sodium (23 mg) per 6 mg dose; this is essentially "sodium-free".

Neulasta is indicated for patients 18 years of age and older.

Follow exactly the administration instructions for Neulasta as indicated by your doctor. Consult with your doctor or pharmacist if you have any doubts. The usual dose is a subcutaneous injection of 6 mg (under the skin), which should be administered at the end of each chemotherapy cycle starting from

24 hours after your last dose of chemotherapy.

Self-Administration of Neulasta

Your doctor may consider it more convenient for you to administer Neulasta yourself. Your doctor or nurse will teach you how to do it. Do not attempt to do it if you have not been taught.

For more information on how to self-administer Neulasta, read section 6 at the end of this prospectus.

Do not shake Neulasta vigorously as it may affect its activity.

If You Use More Neulasta Than You Should

If you use more Neulasta than you should, inform your doctor, pharmacist, or nurse.

If You Forget to Use Neulasta

If you are self-administering and have forgotten to administer your dose of Neulasta, contact your doctor to decide when you should inject the next dose.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

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

Inform your doctor immediately if you experience any of the following side effects:

• swelling that may be associated with urinating less frequently, difficulty breathing, swelling, and a feeling of fullness in the abdomen, and a general feeling of fatigue. These symptoms usually develop very quickly.

These may be symptoms of a rare disease (which can affect up to 1 in 100 people) called "capillary leak syndrome" and may cause blood to leak from a small blood vessel into other parts of your body and require urgent medical attention.

Very common side effects(may affect more than 1 in 10 people):

• bone pain. Your doctor will inform you about what you can take to alleviate the pain.
• nausea and headache.

Common side effects(may affect up to 1 in 10 people):

• with the use of the body injector, skin eruptions, itching, and urticaria (contact dermatitis/local skin reactions) have been observed.
• pain at the injection site.
• with the use of the body injector, reactions at the application site have been observed, which may include redness, bleeding, petechiae, pain, and discomfort.
• general pain and pain in the joints and muscles.
• some changes in your blood may occur, which will be detected through periodic blood tests. You may experience an increase in white blood cells for a short period of time. You may experience a decrease in platelets, which may cause bruising.

Uncommon side effects(may affect up to 1 in 100 people):

• allergic reactions, which include redness and flushing/hives, appearance of hives, and inflammatory skin with itching.
• severe allergic reactions, which include anaphylaxis (weakness, drop in blood pressure, difficulty breathing, facial swelling).
• enlargement of the spleen.
• spleen rupture. Some cases of spleen rupture were fatal. It is essential to contact your doctor immediately if you experience pain in the upper left abdomen or left shoulder, as it may be related to a spleen problem.
• respiratory problems. If you have a cough, fever, and difficulty breathing, consult your doctor.
• cases of Sweet syndrome (painful, inflamed, violaceous lesions on the extremities and, in some cases, on the face and neck, accompanied by fever) have been reported, but may be related to other factors.
• cutaneous vasculitis (inflammation of skin blood vessels).
• damage to the small filters within the kidneys (glomerulonephritis).
• redness at the injection site.
• coughing up blood (hemoptysis).
• hematological disorders (myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML]).

Rare side effects(may affect up to 1 in 1,000 people):

• aortic inflammation (the blood vessel that carries blood from the heart to the rest of the body), see section 2.
• pulmonary hemorrhage.
• Stevens-Johnson syndrome, which may appear as concentric or circular red patches often with central blisters on the trunk, exfoliation, ulcers in the mouth, throat, nose, genitals, and eyes; and may be preceded by fever and flu-like symptoms. Stop using Neulasta if you develop these symptoms and contact your doctor or seek immediate medical attention. See section 2.

Reporting 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 prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about 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 syringe label after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C).

Neulasta may be stored at room temperature (as long as it does not exceed 30°C) for a maximum of 3 days. Once a syringe has been removed from the refrigerator and has reached room temperature (which does not exceed 30°C), it must be used within 3 days or discarded.

Do not freeze. Neulasta may be used in case of accidental freezing, within a period of less than 24 hours.

Store the container in the outer packaging to protect it from light.

Do not use this medication if you observe that the solution is not completely transparent or contains particles.

Medications 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 Neulasta

• The active ingredient is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 ml of solution.
• The other components are sodium acetate, sorbitol (E420), polisorbate 20, and water for injection. See section 2.

Appearance of the product and contents of the pack

Neulasta is a transparent, colourless injectable solution in a pre-filled syringe (6 mg/0.6 ml).

Each pack contains 1 pre-filled syringe of glass with a stainless steel needle and a needle cap.

The pre-filled syringe (packaged with or without a blister) may also be supplied with an automatic needle guard.

Marketing authorisation holder and responsible manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Marketing authorisation holder

Amgen Europe B.V.

Minervum 7061

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 medicine by contacting the local representative of the marketing authorisation holder:

Last update date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the European Medicines Agency websitehttp://www.ema.europa.eu/.

Instructions for self-administering Neulasta in a pre-filled syringe

This section contains information on how to self-administer Neulasta. It is essential that you do not attempt to administer the injection yourself unless you have received specific training from your doctor, nurse, or pharmacist. If you have any doubts about how to administer the injection, ask your doctor, nurse, or pharmacist.

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

You will need to administer the injection into the tissue just below the skin. This is called a subcutaneous injection.

Equipment needed for administration

To administer a subcutaneous injection, you will need:

• a pre-filled syringe of Neulasta; and
• alcohol swabs or similar.

What should you do before administering a subcutaneous injection of Neulasta?

1. Take the pre-filled syringe out of the refrigerator.

1. Do not shake the pre-filled syringe.

1. Do notremove the needle cap until you are ready to administer the injection.

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

1. Check the appearance of Neulasta. It should be a clear, colourless solution. Do not use it if you see particles.

1. To make the injection more comfortable, leave the pre-filled syringe at room temperature for 30 minutes or hold it in your closed hand for a few minutes.Do notheat Neulasta in any other way (e.g., do not put it in the microwave or in hot water).

1. Wash your hands thoroughly.

1. Find a comfortable and well-lit place and place everything you need within reach.

How to prepare the Neulasta injection?

Before administering Neulasta, you should do the following:

1. You may see a small air bubble in the pre-filled syringe. You do not need to remove it before the injection. Injecting the solution with an air bubble is not harmful.

1. You can now use the pre-filled syringe.

Where should you administer the injection?

How to administer the injection?

1. Clean the skin using an alcohol swab.

1. Pinch (without squeezing) the skin using your thumb and index finger. Insert the needle into the skin.

1. Press the plunger head with a gentle, constant pressure. Press the plunger head until all the liquid from the syringe is injected.

1. After injecting the solution, remove the needle and release the skin.

1. If you see blood at the injection site, remove it with a cotton swab or gauze. Do not rub the injection site. If necessary, apply a bandage.

1. Do not use the remaining Neulasta in the syringe.

Remember

Use each syringe for a single injection. If you have any problems, do not hesitate to ask for help and advice from your doctor or nurse.

Disposing of used syringes

• Do not put the needle cap back on the used syringe.

• Keep the used syringes out of sight and reach of children.

• Used syringes must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of unused and unwanted medicines. This will help protect the environment.