Label: information for the user

Neupogen 48 MU (0.96 mg/ml)

injectable solution in preloaded syringe

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 read 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 even if they 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 to help reduce the risk of infections.

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

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

Inform your doctor before starting treatmentif you have:

• thalassemia major, as Neupogen may cause thalassemia crises.
• natural rubber latex allergy. The needle cap of the syringe may contain a type of natural rubber latex that could cause allergic reactions.
• 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 part of the abdomen, pain in the left lower part of the chest or in the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly), or of 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 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.

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 monitor you closely, see section 4 of the leaflet.

If you are a patient with chronic severe 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 particularly 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 must always record the exact product you are using.

Other medicines and Neupogen

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

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 tells you otherwise, you should stop breastfeeding if you use Neupogen.

Driving and operating machines

Neupogen may have a negligible effect on your ability to drive and use machines. This medicine 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 medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, which is essentially "sodium-free".

Neupogen contains sorbitol

This medicine 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 medicine. Patients with HFI cannot digest fructose, which may cause severe adverse effects.

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

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

How is Neupogen administered and how much should I use?

Neupogen is usually administered as a daily injection into the tissue located just below the skin (this is called a subcutaneous injection). It can also be administered as a daily slow 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 a bone marrow transplant after 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.

You or the people taking care of you can learn to administer subcutaneous injections so that you can continue your treatment at home. However, do not attempt to do so unless your healthcare professional has taught you how to do it correctly beforehand.

For 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 control 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 receive 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

Do not increase the dose that your doctor has given you. If you think you have injected a higher dose than you should have, contact your doctor as soon as possible.

If you forgot to use Neupogen

If you have forgotten a dose or injected less dose than you should have, contact your doctor as soon as possible. Do not take a double dose to compensate for the missed doses.

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, 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 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 swelling in the face or ankles, 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, rapid heart rate, confusion or disorientation, difficulty breathing, severe or extreme 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 may 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 part of the 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 the urine (hematuria). Your doctor may perform regular urine tests if you experience this side effect or if you have protein in the urine (proteinuria).

A common side effect of Neupogen is 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
• numbness, especially in the skin (hyposthesia)
• tingling or numbness in the hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• hemoptysis (coughing up blood)
• oral and pharyngeal pain (oral and pharyngeal pain)
• epistaxis (nosebleed)
• constipation
• oral pain
• hepatomegaly (enlarged liver)
• skin rash
• erythema (redness of the skin)
• muscle spasms
• urinary pain (dysuria)
• chest pain
• pain
• generalized weakness (asthenia)
• feeling unwell (malaise)
• peripheral edema (swelling in the hands and feet)
• increased levels of certain enzymes in the blood
• changes in blood biochemistry parameters
• transfusion reactions

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

• increased white blood cell count (leukocytosis)
• allergic reactions (hypersensitivity)
• rejection of the 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 (hyperuricemia) (elevated uric acid in the blood)
• liver damage caused by obstruction of 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 edema)
• pulmonary inflammation (interstitial lung disease)
• abnormal chest X-rays (pulmonary infiltration)
• pulmonary hemorrhage (hemorrhage)
• shortage of oxygen absorption in the lungs (hypoxia)
• rough skin rash (maculo-papular 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):

• intense pain in the 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)
• a change in the way the body regulates fluid volume that may cause swelling (alteration of fluid volume)
• skin vessel inflammation (cutaneous vasculitis)
• painful dark red ulcers on the extremities and, sometimes, on the face and neck that are accompanied by fever (Sweet syndrome)
• exacerbation 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 the bone marrow (extramedullary hematopoiesis)

Reporting of 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 syringe label or 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 (0.6 mg/ml).
• The other components are sodium acetate, sorbitol (E420), polisorbate 80, and water for injectable preparations.

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 preloaded syringe.

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

Holder of the marketing authorization and responsible 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.

Last review date of this leaflet: March 2024

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/.

1. Instructions for injecting Neupogen

This section contains information on how to administer a Neupogen injection.

Important: do not attempt to inject yourself unless your doctor or nurse has taught you how to do it.

Neupogen is injected into the tissue just below the skin. This is called a subcutaneous injection.

Equipment needed

To administer a subcutaneous injection, you will need:

• a new preloaded syringe of Neupogen; and
• alcohol swab or similar

What to do before giving yourself a subcutaneous injection of Neupogen?

1. Take the tray containing the syringe out of the refrigerator and let it come to room temperature for about 30 minutes, or hold it gently in your hands for a few minutes. This will make the injection less uncomfortable.Do notheat Neupogen in any other way (for example, do not heat it in the microwave or in hot water).
2. Do not shake the preloaded syringe.
3. Place the tray in your hand and remove the tray cover.
4. Turn the tray over to place the preloaded syringe in the palm of your hand.
5. Do notremove the needle cover until you are ready for the injection.
6. Check the expiration date on the label of the preloaded syringe (CAD). Do not use it if it has passed the last day of the month indicated.
7. Check the appearance of Neupogen. It should be a clear and colorless liquid. Do not use it if you observe discoloration, turbidity or particles in it.
8. Wash your hands carefully.
9. Find a clean, comfortable and well-lit surface and place all the necessary equipment within reach.

How to prepare the Neupogen injection?

Before injecting Neupogen, you must do the following:

1. To avoid bending the needle, hold the syringe body firmly. Pull the needle cover off without rotating it, as shown in figures 1 and 2.
2. Do not touch the needle or push the plunger.
3. You may observe a small air bubble in the preloaded syringe. Do not remove the air bubble before the injection. Injecting the solution with an air bubble is not harmful.
4. You can now use the preloaded syringe.

Where to give the injection?

The best places to give the injection are the upper part of the thighs and the abdomen. If someone else is giving you the injection, it can also be given in the back of the arms.

You can change the injection site if you observe redness or swelling at the site.

How to give the injection?

1. Clean the skin with an alcohol swab and pinch it (without squeezing) between your thumb and index finger.
2. Insert the needle completely into the skin as your nurse or doctor has shown you.
3. Pull the plunger slowly and steadily, keeping the skin pinched at all times until the syringe is empty.
4. Remove the needle and release the skin.
5. If you observe any blood, you can remove it gently with a little cotton or gauze. Do not rub the injection site. If necessary, you can cover the injection site with a bandage.
6. Use each syringe for only one injection. Do not use the remaining Neupogen that may be left in the syringe.

Remember: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 protective cover back on used needles, as you may accidentally prick yourself.
• Keep used syringes out of reach and sight of children.
• Used syringes should not be thrown away in the trash. Your pharmacist will know how to dispose of used syringes or those that are no longer needed.

This information is intended only for doctors or healthcare professionals:

Neupogen must be diluted in 20 ml of a 5% glucose solution when used as a concentrate for infusion. Please refer to the product technical data sheet for additional information.