Neupogen 30 MU (0.3 mg/ml) solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Neupogen 30 MU (0.3 mg/ml)

injection solution

filgrastim

Read the entire leaflet carefully before you start using this medicine, because 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 you should not give it to others, even if they have the same symptoms as you, because it may 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.

Contents of the leaflet

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

1. What Neupogen is and what it is 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 naturally produced in the body, but can also be produced by 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 for various reasons and makes it harder for your body to fight infections. Neupogen stimulates the bone marrow to rapidly produce new white blood cells.

Neupogen may be used:

• to increase the number of white blood cells after chemotherapy treatment, helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, helping to prevent infections;
• prior to undergoing high-dose chemotherapy, to stimulate the bone marrow to produce more stem cells that can be collected and later returned to you after treatment. These may be collected from yourself or from a donor. The stem cells will then return to the bone marrow and produce blood cells;
• to increase the number of white blood cells in patients with severe chronic neutropenia, helping to prevent infections;
• in patients with advanced HIV infection to help reduce the risk of infections.

2. What you need to know before using Neupogen

Do not use Neupogen

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

Warnings and precautions

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

Inform your doctor before starting treatment if you have:

• sickle cell anemia, as Neupogen could trigger sickle cell crises.
• osteoporosis (bone disease).

Immediately inform your doctor during treatment with Neupogen if you:

• experience 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 may be signs of a serious allergic reaction (hypersensitivity).
• develop swelling of the face or ankles, blood in the urine, brown-colored urine, or notice that you are urinating less than usual (glomerulonephritis).
• have pain in the upper left part of the abdomen, pain in the lower left side of the rib cage, or pain in the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or possible spleen rupture).
• experience unusual bleeding or bruising (these may be symptoms of a low blood platelet count (thrombocytopenia), resulting in reduced blood clotting ability).
• develop symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has rarely been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general malaise, back pain, and elevated inflammatory markers. Inform your doctor if you experience any of these symptoms.

Loss of response to filgrastim

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

Your doctor may wish to monitor you closely; see section 4 of the package leaflet.

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

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

Take special care 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 must always record the exact product you are using.

Other medicines and Neupogen

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

Pregnancy and lactation

Neupogen has not been studied in pregnant or breastfeeding women.

Neupogen is not recommended during pregnancy.

It is important that you inform your doctor if:

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

If you become pregnant while being treated with Neupogen, please inform your doctor.

Unless otherwise instructed by your doctor, you should discontinue breastfeeding if you are using Neupogen.

Driving and use of machines

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

Neupogen contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per vial of 0.3 mg/ml; i.e., 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) must not be given this medicine. Patients with HFI cannot digest fructose, which may lead to serious adverse effects.

You should consult your doctor before receiving this medicine if you (or your child) have HFI or if your child cannot consume sweet foods or drinks due to nausea, vomiting, or unpleasant adverse effects such as bloating, abdominal cramps, or diarrhea.

3. How to use Neupogen

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

How is Neupogen administered and what dose should I use?

Neupogen is usually given as a daily injection into the tissue just beneath the skin (this is called a subcutaneous injection). It may also be given as a daily slow injection into the vein (known as intravenous infusion). The usual dose depends on your condition and body weight. Your doctor will tell you how much Neupogen you should use.

Patients undergoing bone marrow transplantation following chemotherapy:

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

How long should I use Neupogen?

You should continue using Neupogen until your white blood cell count returns to normal. You will have periodic blood tests to monitor your white blood cell count. Your doctor will advise you on how long you will need to continue Neupogen treatment.

Use in children

Neupogen is used to treat children 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 than the prescribed dose, 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 about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible adverse effects

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

Tell your doctor immediately during treatment:

• if you have an allergic reaction including weakness, low blood pressure, breathing difficulty, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and difficulty breathing (dyspnea).

• if you have cough, fever, and breathing difficulties (dyspnea), as these could be signs of acute respiratory distress syndrome (ARDS).

• if you have kidney damage (glomerulonephritis). Renal impairment has been observed in patients receiving Neupogen. Contact your doctor immediately if you experience swelling of the face or ankles, blood in the urine, brown-colored urine, or notice that you are urinating less frequently than normal.

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

• swelling, which may be associated with reduced frequency of urination, difficulty breathing, abdominal swelling and fullness, and a general feeling of fatigue. These symptoms usually develop very rapidly.

These may be symptoms of a condition called "capillary leak syndrome," which can cause blood to leak from small blood vessels into other areas of your body and may require urgent medical attention.

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

• fever, chills, feeling very cold, rapid heart rate, confusion or disorientation, difficulty breathing, extreme pain or discomfort, and wet or sweaty skin.

These may be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a serious infection with a systemic inflammatory response, which can be potentially life-threatening and requires urgent medical attention.

• if you have pain in the upper left part of the abdomen, pain in the lower left side of the rib cage, or shoulder tip pain, as this could indicate a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). Your doctor may perform regular urine tests if you experience this adverse effect or if you have protein in your urine (proteinuria).

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

In healthy stem cell donors, an increase in white blood cells in the blood (leukocytosis) and a decrease in platelets may reduce the blood's ability to clot (thrombocytopenia); both will be monitored by your doctor.

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

• decrease in platelets, reducing the blood's ability to clot (thrombocytopenia)
• low red blood cell count (anemia)
• headache
• diarrhea
• vomiting
• nausea
• weakening or unusual hair loss (alopecia)
• tiredness (fatigue)
• inflammation and swelling of the mucous membrane lining the digestive tract from mouth to anus (mucositis)
• fever (pyrexia)

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• decreased appetite
• difficulty sleeping (insomnia)
• dizziness
• loss of sensation, especially in the skin (hypoaesthesia)
• tingling or numbness in 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)
• nosebleed (epistaxis)
• constipation
• mouth pain
• liver enlargement (hepatomegaly)
• skin rash
• redness of the skin (erythema)
• muscle spasm
• pain when urinating (dysuria)
• chest pain
• pain
• generalised 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 adverse effects (may affect up to 1 in 100 people):

• increase in white blood cells in the blood (leukocytosis)
• allergic reactions (hypersensitivity)
• rejection of transplanted bone marrow against the recipient's own tissues (graft-versus-host disease)
• elevated levels of uric acid in the blood, which may cause gout (hyperuricaemia) (increased uric acid in blood)
• liver damage caused by blockage in the small veins within the liver (veno-occlusive disease)
• abnormal lung function causing shortness of breath (respiratory failure)
• swelling and/or fluid in the lungs (pulmonary oedema)
• inflammation of the lungs (interstitial lung disease)
• abnormal lung X-rays (pulmonary infiltration)
• bleeding from the lungs (pulmonary haemorrhage)
• poor oxygen absorption in the lungs (hypoxia)
• rough skin rashes (maculopapular rash)
• disease causing decreased bone density, making bones weaker, more fragile and more prone to fracture (osteoporosis)
• injection site reaction

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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 packaging to protect it from light.

Accidental freezing of Neupogen does not damage it.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

Do not use this medicine if discoloration, turbidity, or particles are observed; it should be a clear, colourless liquid.

Medicines should not be disposed of via wastewater or household waste. If you are unsure how to dispose of unused medicines and packaging, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of Neupogen

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

Appearance of the product and contents of the pack

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

Neupogen is available in packs of one or five vials. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturing Responsibility

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

The Netherlands

Marketing Authorization Holder

Amgen Europe B.V.
Minervum 7061
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

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, except in Cyprus, Greece, and Italy, where it is known as Granulokine.

Date of the most recent review of this Summary of Product Characteristics:

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

This information is intended for healthcare professionals only:

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