NEUPOGEN 30 MU (0.3 mg/ml) INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Neupogen 30 MU (0.3 mg/ml)

injectable solution

filgrastim

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

1. What is Neupogen and what is it used for

Neupogen is a white blood cell growth factor (granulocyte-colony stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins that are produced naturally in the body, but can also be made using biotechnology for use as medicines. Neupogen works by stimulating the bone marrow to produce more white blood cells.

A reduction in the number of white blood cells (neutropenia) can occur due to various reasons and makes your body less able to fight infections. Neupogen stimulates the bone marrow to produce new white blood cells quickly.

Neupogen can be used:

• to increase the number of white blood cells after chemotherapy to help prevent infections;
• to increase the number of white blood cells after a bone marrow transplant to help prevent infections;
• before receiving high-dose chemotherapy so that the bone marrow produces more stem cells that can be collected and given back to you after treatment. These stem cells can be collected from you or a donor. The stem cells will then return to the bone marrow and produce blood cells;
• to increase the number of white blood cells if you have severe chronic neutropenia to help prevent infections;
• in patients with advanced HIV infection to help reduce the risk of infections.

2. What you need to know before you use Neupogen

Do not use Neupogen

• if you are allergic to filgrastim or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor, pharmacist, or nurse before you start using Neupogen.

Tell your doctor before you start treatment if you have:

• sickle cell anaemia, as Neupogen could cause you to have a sickle cell crisis.
• osteoporosis (bone disease).

Tell your doctor immediately if during treatment with Neupogen:

• 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, these can be signs of a severe allergic reaction (hypersensitivity).
• you experience swelling of the face or ankles, blood in the urine or brown colour in the urine or if you notice that you urinate less often than normal (glomerulonephritis).
• you have pain in the upper left side of your abdomen (stomach), pain in the lower left side of the rib cage or pain in the left shoulder tip (these can be symptoms of an enlarged spleen (splenomegaly) or a possible rupture of the spleen).
• you experience bleeding or unusual bruising (these can be symptoms of a low blood platelet count (thrombocytopenia), with a reduced ability of the blood to clot).
• if you have symptoms of inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), this has rarely been reported in patients with cancer and in healthy donors. Symptoms can include fever, abdominal pain, general feeling of being unwell, back pain and increased inflammatory markers. Tell your doctor if you have these symptoms.

Loss of response to filgrastim

If you experience a loss of response or if it is not possible to maintain a response to treatment with filgrastim, your doctor will investigate the causes including whether you have developed antibodies that could neutralise the activity of filgrastim.

Your doctor may want to closely monitor you, see section 4 of the leaflet.

If you are a patient with severe chronic neutropenia, you may be at risk of developing blood cancer (leukaemia, myelodysplastic syndrome (MDS)). You should discuss with your doctor the risk of developing blood cancer and what examinations should be performed. If you develop blood cancer, you should not use Neupogen, unless your doctor advises you to.

If you are a stem cell donor, you must be between 16 and 60 years of age.

Be careful with other products that stimulate white blood cells

Neupogen belongs to a group of products that stimulate the production of white blood cells. The healthcare professional treating you should always record the exact product you are using.

Other medicines and Neupogen

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

Pregnancy and breast-feeding

Neupogen has not been tested in pregnant or breast-feeding women.

Neupogen is not recommended during pregnancy.

It is important that you tell your doctor:

• if you are pregnant or breast-feeding;
• if you think you may be pregnant; or
• if you are planning to have a baby.

If you become pregnant during treatment with Neupogen, please tell your doctor.

Unless your doctor tells you otherwise, you must stop breast-feeding if you use Neupogen.

Driving and using machines

Neupogen may have a minor influence on your ability to drive and use machines. This medicine can cause dizziness. It is recommended that you wait and observe how you react after administration of Neupogen before driving or using machines.

Neupogen contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial of 0.3 mg/ml; this is essentially “sodium-free”.

Neupogen contains sorbitol

This medicine contains 50 mg of sorbitol in each ml.

Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) should not receive this medicine. Patients with HFI cannot digest fructose, which can cause serious side effects.

You should consult your doctor before receiving this medicine if you (or your child) have HFI or if your child cannot eat foods or drinks containing sugars because they cause nausea, vomiting or unpleasant side effects such as bloating, stomach cramps or diarrhoea.

3. How to use Neupogen

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor, nurse or pharmacist again.

How is Neupogen administered and what dose should you use?

Neupogen is usually given as a daily injection under the skin (this is called a subcutaneous injection). It can also be given as a daily slow injection into a vein (this is called an intravenous infusion). The usual dose varies depending on your illness and weight. Your doctor will tell you what dose of Neupogen you should use.

Patients undergoing bone marrow transplantation after chemotherapy:

You will usually receive your first dose of Neupogen at least 24 hours after chemotherapy and at least 24 hours after bone marrow transplantation.

For how long will you need to use Neupogen?

You will need to use Neupogen until your white blood cell count is normal. You will have regular blood tests to check the number of white blood cells in your body. Your doctor will tell you for how long you will need to use Neupogen.

Use in children

Neupogen is used to treat children who are receiving chemotherapy or who have a very low white blood cell count (neutropenia). The dose for children receiving chemotherapy is the same as for adults.

If you use more Neupogen than you should

If you think you have injected more Neupogen than you should, contact your doctor as soon as possible.

If you forget to use Neupogen

If you miss an injection, contact your doctor as soon as possible.

If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.

4. Possible side effects

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

Tell your doctor immediatelyduring treatment:

• if you have an allergic reaction that includes weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat and difficulty breathing (dyspnoea).
• if you have cough, fever and breathing difficulties (dyspnoea) as these could be signs of acute respiratory distress syndrome (ARDS).
• if you have kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving Neupogen. Tell your doctor immediately if you experience swelling of the face or ankles, blood in the urine or brown colour in the urine or if you notice that you urinate less often than normal.
• if you have any of the following side effects or a combination of them:

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

These can be symptoms of a condition called “capillary leak syndrome” which can cause blood to leak from small blood vessels into other parts of your body and requires urgent medical attention.

• if you have any of the following side effects or a combination of them:

• fever, or chills, or feeling very cold, increased heart rate, confusion or disorientation, difficulty breathing, severe pain or discomfort and sweaty or clammy skin.

These can be symptoms of a condition called “sepsis” (also called “blood poisoning”), a severe infection with inflammation throughout the body, which can be life-threatening and requires urgent medical attention.

• if you have pain in the upper left side of your abdomen (stomach), pain in the lower left side of the rib cage or pain in the left shoulder tip, as these could be symptoms of an enlarged spleen (splenomegaly) or a possible rupture of the spleen.
• if you are being treated for severe chronic neutropenia and have blood in the urine (haematuria). Your doctor may perform regular urine tests if you have this side effect or if you have protein in the urine (proteinuria).

A common side effect of Neupogen is pain in the muscles or bones (musculoskeletal pain), which can be relieved by taking ordinary painkillers (analgesics). Patients undergoing stem cell or bone marrow transplantation may develop graft-versus-host disease (GVHD) - this is a reaction of the donor cells against the patient receiving the transplant, whose signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and sores in the mouth, gut, liver, skin, or eyes, lungs, vagina and joints.

In healthy stem cell donors, an increase in white blood cells in the blood (leucocytosis) and a decrease in platelets which can reduce the ability of the blood to clot (thrombocytopenia) may occur, both will be monitored by your doctor.

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

• decrease in platelets reducing the ability of the blood to clot (thrombocytopenia)
• low red blood cell count (anaemia)
• headache
• diarrhoea
• vomiting
• nausea
• unusual hair loss (alopecia)
• fatigue
• inflammation and swelling of the mucous membrane of the digestive tract from the mouth to the anus (mucositis)
• fever (pyrexia)

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

• inflammation of the lungs (bronchitis)
• infection of the upper respiratory tract
• infection of the urinary tract
• decreased appetite
• difficulty sleeping (insomnia)
• dizziness
• loss of sensation, especially in the skin (hypoesthesia)
• tingling or numbness of the hands or feet (paraesthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (haemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleeds (epistaxis)
• constipation
• mouth pain
• enlargement of the liver (hepatomegaly)
• skin rash
• redness of the skin (erythema)
• muscle spasms
• pain when urinating (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• feeling unwell (malaise)
• swelling of the hands and feet (peripheral oedema)
• increase in certain enzymes in the blood
• changes in blood biochemical parameters
• transfusion reactions

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

• increase in white blood cells in the blood (leucocytosis)
• allergic reactions (hypersensitivity)
• rejection of the transplanted bone marrow against the patient’s own tissues (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricaemia) (elevated uric acid in the blood)
• damage to the liver caused by a blockage in the small veins within the liver (veno-occlusive disease)
• abnormal functioning of the lungs, causing shortness of breath (respiratory failure)
• swelling and/or fluid in the lungs (pulmonary oedema)
• inflammation of the lungs (interstitial lung disease)
• abnormal chest X-rays (pulmonary infiltrates)
• bleeding in the lungs (pulmonary haemorrhage)
• lack of oxygen in the lungs (hypoxia)
• rough skin rash (maculopapular rash)
• disease that causes a decrease in bone density, making them weaker, more fragile and more prone to breaking (osteoporosis)
• reaction at the injection site

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

• severe pain in the bones, chest, gut or joints (sickle cell crisis)
• sudden life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling of the joints, similar to gout (pseudogout)
• a change in the way the body regulates body fluids that can cause swelling (fluid volume alteration)
• inflammation of the blood vessels in the skin (cutaneous vasculitis)
• painful dark red ulcers on the limbs and sometimes on the face and neck that are accompanied by fever (Sweet’s syndrome)
• worsening of rheumatoid arthritis
• unusual change in urine
• decreased bone density
• inflammation of the aorta (the blood vessel that carries blood from the heart to the rest of the body), see section 2.
• formation of blood cells outside of the bone marrow (extramedullary haematopoiesis)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Surveillance System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Neupogen

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

Store in a refrigerator (2°C – 8°C).

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

Accidental freezing of Neupogen does not affect it.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Do not use this medicine if you notice discolouration, turbidity or particles; it should be a clear and colourless liquid.

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. Contents of the pack and other information

What Neupogen contains

• The active substance is filgrastim 30 million units (0.3 mg/ml) in a 1 ml vial.
• The other ingredients are sodium acetate, sorbitol (E420), polysorbate 80 and water for injections.

Appearance and packaging

Neupogen is a clear and colourless injectable solution (injectable) / concentrate for solution for infusion (sterile concentrate) in a vial.

Neupogen is available in packs of 1 or 5 vials. Not all pack sizes may be marketed.

Marketing authorisation 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

Local Representative of the Marketing Authorization Holder

Spain

Amgen, S.A.

Plaça del Gas, 1

Torre Marenostrum

Torre A, planta 20

08003 Barcelona

Tel: 93 600 18 60

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the name Neupogen, with the exception of Cyprus, Greece, and Italy, where it is called Granulokine.

Date of the last revision of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended solely for healthcare professionals:

Neupogen must be diluted in 20 ml of a 5% glucose solution when used as a concentrate for solution for infusion. Please consult the Product Characteristics for additional information.