Label: information for the user

Neupogen 30 MU (0.3 mg/ml)

injectable solution

filgrastim

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 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 label. See section 4.

Neupogen is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medications called cytokines. Growth factors are proteins that are produced naturally in the body, but can also be obtained through biotechnology for use as medications. Neupogen acts by causing 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 your body less able to fight off 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 treatment to help prevent infections;
• to increase the number of white blood cells after a bone marrow transplant to help prevent infections;
• before undergoing high-dose chemotherapy so that the bone marrow can produce more stem cells that can be collected and returned after treatment. These can be taken from yourself or a donor. The stem cells will then return to the bone marrow and produce white 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 tohelp reduce the risk of infections.

Do not use Neupogen

• If you are allergic to filgrastim or any of the other components of this medication (listed in section 6).

Warnings and precautions

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

Inform your doctor before starting treatmentif you have:

• sickle cell anemia, as Neupogen may cause sickle cell crises.
• osteoporosis (bone disease).

Inform your doctor immediately if during treatment with Neupogen:

• you experience sudden signs of allergy, such as skin rash, itching, or hives, swelling of the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or difficulty breathing, which may be signs of a severe allergic reaction (hypersensitivity).
• you experience swelling in the face or ankles, blood in the urine, or brown-colored urine, or if you notice that you urinate less frequently than normal (glomerulonephritis).
• you experience pain in the upper left abdomen, pain in the left lower chest, or in the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly), or a possible spleen rupture).
• you experience unusual bleeding or bruising (these may be symptoms of a decrease in platelet count (thrombocytopenia), with reduced blood clotting ability).
• if you experience symptoms of aorta inflammation (the large blood vessel that carries blood from the heart to the rest of the body), which is rarely 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.

Loss of response to filgrastim

If you experience a loss of response or if you are unable to maintain the response to treatment with filgrastim, your doctor will investigate the causes, including whether you have developed antibodies that may neutralize 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 (leukemia, myelodysplastic syndrome (MDS)). You should consult with your doctor about the risk of developing blood cancer and what investigations should be performed. If you develop blood cancer, you should not use Neupogen, except if your doctor advises you to.

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

Be especially 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 attending to you must always record the exact product you are using.

Other medications and Neupogen

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

Pregnancy and breastfeeding

Neupogen has not been tested in pregnant women or breastfeeding women.

Neupogen is not recommended during pregnancy.

It is essential that you inform your doctor if:

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

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

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

Driving and operating machinery

Neupogenmay have a negligibleinfluenceon your ability to drive and use machines.This medication may cause dizziness.It is recommended that you wait and observe how you react after the administration of Neupogen before driving or using machines.

Neupogen contains sodium

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

Neupogen contains sorbitol

This medication contains 50 mg of sorbitol per 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 medication. Patients with HFI cannot digest fructose, which may cause severe adverse effects.

You should consult with your doctor before receiving this medication if you (or your child) have HFI or if your child cannot eat sweet foods or drinks because they experience nausea, vomiting, or unpleasant side effects such as bloating, abdominal cramps, or diarrhea.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor, nurse, or pharmacist again.

How is Neupogen administered and what dose should I use?

Neupogen is usually administered as a daily injection into the tissue just below the skin (this is known as a subcutaneous injection). It can also be administered as a slow daily injection into the vein (this is known as an intravenous infusion). The usual dose varies depending on your illness and weight. Your doctor will tell you how much 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.

How long should I use Neupogen?

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

Use in children

Neupogen is used to treat children who are receiving chemotherapy or have an extremely 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 a higher dose than you should, contact your doctor as soon as possible.

If you forget to use Neupogen

If you have forgotten a dose, contact your doctor as soon as possible.

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

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

Inform your doctor immediatelyduring treatment:

• if you have an allergic reaction that includes weakness, decreased blood pressure, difficulty breathing, facial swelling (anaphylaxis), skin rash, itchy rash (urticaria), facial swelling, lip, mouth, tongue, or throat swelling (angioedema) and difficulty breathing (dyspnea).
• if you have cough, fever, and difficulty breathing (dyspnea) as they may be signs of acute respiratory distress syndrome (ARDS).
• if you have kidney damage (glomerulonephritis). Renal deterioration has been observed in patients receiving Neupogen. Consult your doctor immediately if you experience facial or ankle swelling, blood in the urine, or brown-colored urine, or if you notice that you urinate less frequently than usual.
• if you have any of the following side effects or a combination of them:

• swelling, which 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 condition 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.

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

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

These may be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a severe infection with a systemic inflammatory reaction, which can be potentially fatal and requires urgent medical attention.

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

Neupogen is a common side effect of muscle or bone pain (musculoskeletal pain), which can be relieved by taking usual pain medications (analgesics). Patients undergoing a stem cell or bone marrow transplant may develop graft-versus-host disease (GVHD) - this is a reaction of the donor cells against the recipient, whose signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and lesions in the mouth, intestine, liver, skin, or eyes, lungs, vagina, and joints.

In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a decrease in plateletsmay be considered to reduce theblood clotting capacity of your blood (thrombocytopenia), both of which will be monitored by your doctor.

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

• decreased platelets reducing blood clotting capacity (thrombocytopenia)
• low red blood cell count (anemia)
• headache
• diarrhea
• vomiting
• nausea
• unusual hair loss (alopecia)
• fatigue (fatigue)
• inflammation and swelling of the digestive tract mucosa from mouth to anus (mucosal inflammation)
• fever (pyrexia)

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

• pulmonary inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• decreased appetite
• difficulty sleeping (insomnia)
• dizziness
• loss of sensation, especially in the skin (hyposthesia)
• tingling or numbness in the hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• blood cough (hemoptysis)
• mouth and throat pain (orofacial pain)
• nasal bleeding (epistaxis)
• constipation
• mouth pain
• enlarged liver (hepatomegaly)
• skin rash
• skin redness (erythema)
• muscle spasms
• urination pain (dysuria)
• chest pain
• pain
• generalized weakness (asthenia)
• feeling unwell (malaise)
• swelling in the hands and feet (peripheral edema)
• increased certain enzymes in the blood
• changes in blood biochemical parameters
• transfusion reactions

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

• intense bone, chest, intestine, or joint pain (sickle cell anemia crisis)
• life-threatening allergic reaction (anaphylactic reaction)
• joint pain and swelling similar to gout (pseudogout)
• a change in the way the body regulates fluid volume that may cause swelling (fluid volume alteration)
• skin blood vessel inflammation (cutaneous vasculitis)
• painful, dark red ulcers on the extremities and sometimes on the face and neck that occur with fever (Sweet syndrome)
• worsening of rheumatoid arthritis
• unusual urine changes
• decreased bone density
• aorta inflammation (the blood vessel that carries blood from the heart to the rest of the body), see section 2.
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis)

Reporting side effects

If you experience any type of side effect, consult your doctor 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 Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. 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.

Store in refrigerator (2°C–8°C).

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

Accidental freezing of Neupogen does not damage it.

Do not use this medication after the expiration date that appears on the container after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe discoloration, cloudiness, or particles; it should be a transparent and colorless liquid.

Medications should not be disposed of through drains or in the trash.If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. This will help protect the environment.

Composition of Neupogen

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

Appearance of the product and contents of the package

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

Neupogen is available in packages of one or five vials. Some package sizes may only be marketed.

Holder of the marketing authorization and manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Holder of the marketing authorization

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 holder of the marketing authorization

Spain

Amgen, S.A.

Plaça del Gas, 1

Torre Marenostrum

Torre A, floor 20

08003 Barcelona

Phone: 93 600 18 60

This medicine 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 called Granulokine.

Revision date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.

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This information is intended solely for doctors or healthcare professionals:

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