NEULASTA 6 mg INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Neulasta 6 mg Solution for Injection

pegfilgrastim

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Neulasta and what is it used for
2. What you need to know before you use Neulasta
3. How to use Neulasta
4. Possible side effects
5. Storage of Neulasta
6. Contents of the pack and other information

1. What is Neulasta and what is it used for

Neulasta contains the active substance pegfilgrastim. Pegfilgrastim is a protein produced by biotechnology in the bacterium E. coli. Pegfilgrastim belongs to a group of proteins called cytokines and is very similar to a natural protein (granulocyte colony-stimulating factor) produced by the 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 can occur as a result of cytotoxic chemotherapy (medicines that destroy rapidly dividing cells). White blood cells are important cells that help fight infections. These cells are sensitive to the effects of chemotherapy, which can cause their numbers to decrease. If the number of white blood cells becomes too low, there may not be enough to fight off bacteria, which can lead to a greater risk of 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 to help fight infections.

2. What you need to know before you use Neulasta

Do not use Neulasta

• if you are allergic to pegfilgrastim, filgrastim, or any of the other ingredients of this medicine

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Neulasta:

• if you experience an allergic reaction that includes weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), redness, and itching, skin rash, and itching in areas of the skin.
• if you are allergic to latex. The needle cap of the pre-filled syringe contains a latex derivative that may cause severe allergic reactions.
• if you are allergic to acrylic adhesives. The on-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 side effects:

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

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

• if you have pain in the upper left abdomen or pain in the tip of the shoulder. This may be a sign of a problem with the spleen (splenomegaly).
• if you have 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 changes in your blood cell count (e.g., increased white blood cell count or anemia) or a decrease in your blood platelet count, which can reduce the ability of your blood to clot (thrombocytopenia). Your doctor may want to monitor you more closely.
• if you have sickle cell anemia. Your doctor may monitor your disease more closely.
• if you are a cancer patient with breast or lung cancer, the combined treatment of Neulasta with chemotherapy and/or radiotherapy may increase the risk of developing a pre-cancerous hematological disorder called myelodysplastic syndrome (MDS) or a hematological malignancy called acute myeloid leukemia (AML). Symptoms may include tiredness, fever, easy bruising or bleeding.
• if you have sudden signs of allergy, such as rash, itching, or hives on the skin, swelling of the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or difficulty breathing, may be signs of a severe allergic reaction.
• if you have symptoms of aortic inflammation (the large blood vessel that carries blood from the heart to the rest of the body), which has been rarely reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general malaise, back pain, and increased inflammatory markers. Inform your doctor if you experience these symptoms.

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

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

You should discuss with your doctor the risk of developing blood cancer. If you develop or may develop blood cancer, you should not use Neulasta, unless your doctor advises you to.

Loss of response to pegfilgrastim

If you experience a loss of response or if you do not achieve a 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 medicines and Neulasta

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine. Neulasta has not been used in pregnant women. It is important that you inform your doctor if:

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

Unless your doctor tells you otherwise, you must stop breastfeeding if you use Neulasta.

Driving and using machines

Neulasta has no or negligible influence on the ability to drive and use machines.

Neulasta contains sorbitol (E420) and sodium

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

3. How to use Neulasta

Neulasta is indicated in patients aged 18 years and older.

Follow the instructions for administration of Neulasta exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure. The usual dose is a single subcutaneous injection of 6 mg (under the skin), which should be administered at the end of each chemotherapy cycle, at least 24 hours after your last dose of chemotherapy.

Self-injection of Neulasta

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

For further instructions on how to self-inject Neulasta, read section 6 at the end of this leaflet.

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

If you use more Neulasta than you should

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

If you forget to use Neulasta

If you are self-injecting 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 further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you experience any or a combination of the following side effects:

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

These may be symptoms of a disease that occurs infrequently (which may affect up to 1 in 100 people) called "Capillary Leak Syndrome" and may cause blood to leak from small blood vessels 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 relieve the pain.
• nausea and headache.

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

• with the use of the on-body injector, skin rash, itching, and hives (contact dermatitis/local skin reactions) have been observed.
• injection site pain.
• with the use of the on-body injector, reactions at the application site have been observed, which may include redness, bleeding, bruising, pain, and discomfort.
• general pain and pain in the joints and muscles.
• some changes in your blood may occur, which will be detected by regular blood tests. The number of white blood cells may increase for a short period. The number of platelets may decrease, which can cause bruising.

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

• allergic reactions, including redness and flushing, rash, and skin inflammation with itching.
• severe allergic reactions, including anaphylaxis (weakness, low blood pressure, difficulty breathing, facial swelling).
• enlargement of the spleen.
• splenic rupture. Some cases of splenic rupture were fatal. It is important that you contact your doctor immediately if you notice pain in the upper left abdomen or left shoulder, as these may be related to a problem with your spleen.
• respiratory problems. If you have a cough, fever, and difficulty breathing, consult your doctor.
• cases of Sweet's syndrome (painful, inflamed, purple-colored lesions on the limbs and sometimes on the face and neck, accompanied by fever) have been reported, but may be related to other factors.
• cutaneous vasculitis (inflammation of the blood vessels in the skin).
• damage to the small filters inside the kidneys (glomerulonephritis).
• redness at the injection site.
• bleeding from the lungs (pulmonary hemorrhage).
• 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 large blood vessel that carries blood from the heart to the rest of the body), see section 2.
• bleeding from the lungs (pulmonary hemorrhage).
• Stevens-Johnson syndrome, which may appear as red, circular, or concentric 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 medical attention immediately. See section 2.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Neulasta

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

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pre-filled syringe after EXP. The expiry date refers to the last day of the month shown.

Store in a refrigerator (2°C - 8°C).

Neulasta may be stored at room temperature (below 30°C) for a maximum of 3 days. Once a pre-filled syringe has been removed from the refrigerator and reached room temperature (below 30°C), it must be used within 3 days or discarded.

Do not freeze. Neulasta may be used after accidental freezing for a period of less than 24 hours.

Keep the container in the outer carton to protect from light.

Do not use this medicine if you notice that the solution is not entirely clear or contains particles.

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 protect the environment.

6. Container Contents and Additional Information

Composition of Neulasta

• The active ingredient is pegfilgrastim. Each prefilled syringe contains 6 mg of pegfilgrastim in 0.6 ml of solution.
• The other components are sodium acetate, sorbitol (E420), polysorbate 20, and water for injectable preparations. See section 2.

Appearance of the Product and Container Contents

Neulasta is a clear, colorless injectable solution in a prefilled syringe (6 mg/0.6 ml).

Each container contains 1 prefilled glass syringe with a stainless steel needle and a needle cap.

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

Marketing Authorization Holder and Manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Marketing Authorization 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 medication by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:

Other Sources of Information

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

Instructions for Injecting Neulasta using a Prefilled Syringe

This section contains information on how to self-inject Neulasta. It is important that you do not attempt to self-inject unless you have received specific training on how to do so 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 injecting you use the Neulasta Prefilled Syringe?

The injection will be given into the tissue under the skin. This is called a subcutaneous injection.

Equipment Needed for Administration

To give a subcutaneous injection, you will need:

• a Neulasta prefilled syringe; and
• alcohol swab or similar.

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

1. Take the prefilled syringe out of the refrigerator.

1. Do not shake the prefilled syringe.

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

1. Check the expiration date (EXP) on the prefilled syringe label. Do not use it if it has passed the last day of the month shown.

1. Check the appearance of Neulasta. It should be a clear and colorless liquid. Do not use it if you see particles.

1. To make the injection more comfortable, let the prefilled syringe come to room temperature for 30 minutes or hold it in your closed hand for a few minutes. Do notheat Neulasta in any other way (for example, do not put it in the microwave or in hot water).

1. Wash your hands carefully.

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

How to prepare the Neulasta injection?

Before injecting Neulasta, you must do the following:

1. There may be a small air bubble in the prefilled syringe. It is not necessary to remove it before injection. Injecting the solution with an air bubble is not harmful.

1. The prefilled syringe is now ready to use.

Where should you inject Neulasta?

How to give the injection?

1. Clean the skin with 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 light and constant pressure. Press the plunger head until all the liquid is injected from the syringe.

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

1. If you see a drop of blood at the injection site, remove it with a cotton ball or gauze. Do not rub the injection site. If necessary, you can cover the injection site with a band-aid.

1. Do not use the remaining Neulasta left 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 cap back on used needles.

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

• Used syringes must be disposed of according to local regulations. Ask your pharmacist how to dispose of containers and medications that are no longer needed. This will help protect the environment.