Neupogen

Leaflet attached to the packaging: patient information

Neupogen, 600 micrograms/ml (30 million IU/0.5 ml), solution for injection in a pre-filled syringe
Neupogen, 960 micrograms/ml (48 million IU/0.5 ml), solution for injection in a pre-filled syringe
filgrastim

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Neupogen and what is it used for
• 2. Important information before using Neupogen
• 3. How to use Neupogen
• 4. Possible side effects
• 5. How to store Neupogen
• 6. Package contents and other information
• 7. Instructions for injecting Neupogen

1. What is Neupogen and what is it used for

Neupogen is a white blood cell growth factor (granulocyte colony-stimulating factor) belonging to a group of medicines called cytokines. Growth factors are proteins produced naturally in the body that can be produced and used as medicines using biotechnological methods.
Neupogen stimulates the bone marrow to produce more white blood cells.
A decrease in the number of white blood cells (neutropenia) can occur for several reasons. Neutropenia weakens the body's ability to fight infection. Neupogen stimulates the bone marrow to quickly produce new white blood cells.
Neupogen can be used:

• to increase the number of white blood cells after chemotherapy, in order to prevent the development of infections;
• to increase the number of white blood cells after bone marrow transplantation, in order to prevent the development of infections;
• before high-dose chemotherapy to stimulate the bone marrow to produce more stem cells that can be harvested from the patient and then transplanted after the end of treatment. Stem cells can be harvested from the patient themselves or from a donor. Transplanted stem cells return to the bone marrow and produce blood cells;
• to increase the number of white blood cells in people with severe chronic neutropenia, in order to prevent the development of infections;
• in patients with advanced HIV infection to reduce the risk of developing infections.

2. Important information before using Neupogen

When not to use Neupogen

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

Warnings and precautions

Before starting treatment with Neupogen, discuss it with your doctor, pharmacist or nurse.
Before starting treatment, inform your doctor if:

• sickle cell anemia has been diagnosed; Neupogen may exacerbate the disease.
• there is an allergy to natural rubber (latex). The needle shield attached to the end of the pre-filled syringe is made of natural rubber and may cause an allergic reaction.
• osteoporosis (bone disease) has been diagnosed.

Tell your doctor immediately if, during treatment with Neupogen, the patient experiences:

• sudden symptoms of hypersensitivity, such as: rash, itching of the skin or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing, as these may be symptoms of a severe allergic reaction (hypersensitivity),
• swelling of the face or ankles, blood in the urine or urine discolored to brown, or urine is excreted in smaller amounts than usual (kidney damage),
• pain in the upper left part of the abdomen, pain on the left side in the rib area or pain at the top of the left shoulder [may be symptoms of spleen enlargement (splenomegaly) or possible spleen rupture],
• unusual bleeding or bruising [may be symptoms of a decrease in platelet count (thrombocytopenia) and decreased blood clotting ability],
• in patients with cancer and in healthy donors, rare symptoms of aortic inflammation (a large blood vessel that carries blood from the heart to the rest of the body) have been observed. Symptoms may include: fever, abdominal pain, malaise, back pain and increased inflammation markers. If the patient experiences such symptoms, they should inform their doctor.

Loss of response to filgrastim

If the patient experiences a loss of response or inability to maintain a response to filgrastim treatment, the doctor will investigate the causes, including possible production of antibodies that neutralize the action of filgrastim.
The doctor may recommend closer monitoring of the patient, see section 4 of the leaflet.
In patients with severe chronic neutropenia, there is a risk of developing blood cancer [leukemia, myelodysplastic syndrome (MDS)]. The risk of developing blood cancer and what tests should be performed should be discussed with the doctor. If the patient develops blood cancer or is likely to develop it, they should not use Neupogen, unless their doctor recommends it.
Stem cell donors can only be people between 16 and 60 years old.

Be careful when using other white blood cell-stimulating products

Neupogen belongs to a group of medicines that stimulate the production of white blood cells. The attending physician should always clearly record the trade name of the medicine being administered to the patient.

Neupogen and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

Pregnancy and breastfeeding

No studies have been conducted with Neupogen in pregnant or breastfeeding women. Neupogen should not be used during pregnancy.
It is essential to inform the doctor:

• if the patient is pregnant or breastfeeding,
• if they suspect they may be pregnant; or
• if they plan to have a child. If the patient becomes pregnant while using Neupogen, they should inform their doctor.

If the doctor does not recommend otherwise, breastfeeding should be stopped during treatment with Neupogen.

Driving and using machines

Neupogen may have a minor effect on the ability to drive and use machines. This medicine may cause dizziness. It is recommended that the patient waits and sees how they feel after taking Neupogen before driving a vehicle or operating machinery.

Neupogen contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e., the medicine is considered "sodium-free".

Neupogen contains sorbitol

The medicine contains 50 mg of sorbitol in each ml.
Sorbitol is a source of fructose. If the patient has been diagnosed with hereditary fructose intolerance, a rare genetic disorder, they should not take this medicine. In patients with hereditary fructose intolerance, the body does not break down the fructose contained in this medicine, which can cause severe side effects.
Tell the doctor before taking this medicine if the patient has hereditary fructose intolerance or if they cannot take sweet foods or drinks due to nausea, vomiting, or unpleasant side effects such as bloating, stomach cramps, or diarrhea.

3. How to use Neupogen

This medicine should always be used exactly as prescribed by the doctor. In case of doubts, consult a doctor, nurse or pharmacist.

How Neupogen is administered and what dose is used

Neupogen is usually administered daily by injection into the tissue just under the skin (subcutaneous injection). The medicine can also be administered daily by slow injection into a vein (intravenous infusion). The dose depends on the type of disease and the patient's body weight.
The doctor will inform the patient about the dose of the medicine to be taken.
Patient undergoing bone marrow transplantation after chemotherapy:
Usually, the patient receives the first dose of Neupogen at least 24 hours after chemotherapy or at least 24 hours after bone marrow transplantation.
The patient or their caregivers may be trained to perform subcutaneous injections to continue treatment at home. The patient should not attempt to do this unless they have been properly trained by their doctor.

How long to use Neupogen

Neupogen should be used until the white blood cell count returns to normal. Regular blood tests will be performed to check the white blood cell count in the body. The doctor will inform the patient how long to use Neupogen.

Use in children

Neupogen is used in children receiving chemotherapy or suffering from severe chronic neutropenia (significant decrease in white blood cell count). The dosage in children receiving chemotherapy is the same as in adults.

Using a higher dose of Neupogen than recommended

Do not exceed the dose prescribed by the doctor. If a higher dose than recommended is suspected to have been administered, contact the doctor as soon as possible.

Missing a dose of Neupogen

If a dose is missed or a smaller dose than recommended is administered, inform the doctor as soon as possible. Do not take a double dose to make up for the missed dose.
In case of any further doubts about using this medicine, consult a doctor, nurse or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell the doctor immediatelyif, during treatment, the patient experiences:

• an allergic reaction, including weakness, sudden drop in blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, itching skin rash (hives), swelling of the face, lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnea).
• cough, fever and breathing problems (dyspnea), as these may be symptoms of acute respiratory distress syndrome.
• kidney damage (kidney damage). Kidney damage has occurred in patients receiving Neupogen. Contact the doctor immediately if the patient experiences swelling of the face or ankles, blood in the urine or urine discolored to brown, or urine is excreted in smaller amounts than usual.
• any of the following side effects or a combination of them:
• swelling or swelling that may be associated with less frequent urination, difficulty breathing, abdominal swelling or a feeling of fullness and general feeling of fatigue. These symptoms usually develop rapidly.

These may be symptoms of a disease called "capillary leak syndrome", which causes blood to leak from small blood vessels into the patient's body and requires immediate medical attention.

• any of the following symptoms:
• fever or chills or a feeling of piercing cold, rapid heart rate, confusion, disorientation, shortness of breath, severe pain or discomfort and sweaty or moist skin. These may be symptoms of a disease called "sepsis" (also known as blood poisoning), a serious infection that can be life-threatening and requires immediate medical attention.
• pain in the upper left part of the abdomen, pain on the left side in the rib area or pain at the top of the left shoulder, as this may indicate spleen problems [enlargement of the spleen (splenomegaly) or possible spleen rupture].
• in patients with severe chronic neutropenia, blood in the urine (hematuria). The doctor may recommend regular urine tests if the patient experiences this side effect or if protein is present in the urine (proteinuria).

A common side effect of Neupogen is muscle or bone pain (musculoskeletal pain), which can be relieved by taking commonly used painkillers. In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease may occur - this is a reaction of the donor's cells against the recipient's body; symptoms and signs of this disease include a rash on the palms of the hands or soles of the feet and ulcers and pain in the mouth, intestines, liver, skin or eyes, lungs, vagina and joints.
In healthy stem cell donors, an increase in white blood cell count (leukocytosis) and a decrease in platelet count (thrombocytopenia) have been observed, which is associated with a decrease in blood clotting ability; this will be monitored by the doctor.
Very common side effects(may affect more than 1 in 10 people):

• decrease in platelet count, which reduces the ability to clot blood (thrombocytopenia)
• decrease in red blood cell count (anemia)
• headache
• diarrhea
• vomiting
• nausea
• unusual hair loss or weakening (alopecia)
• fatigue
• pain and swelling of the mucous membrane of the digestive tract from the mouth to the anus (mucositis)
• fever

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• decreased appetite
• sleep disorders (insomnia)
• dizziness
• numbness, especially in the skin (hypoesthesia)
• tingling or numbness of the hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleeds
• constipation
• pain in the mouth
• enlargement of the liver (hepatomegaly)
• rash
• redness of the skin (erythema)
• muscle spasms
• pain when urinating (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• general malaise
• swelling of the hands and feet (peripheral edema)
• increased activity of some enzymes in the blood
• changes in blood biochemical test results
• transfusion reaction Uncommon side effects(may affect up to 1 in 100 people):
• increased white blood cell count (leukocytosis)
• allergic reaction (hypersensitivity)
• bone marrow transplant rejection (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid levels in the blood)
• liver damage caused by blockage of small veins in the liver (hepatic veno-occlusive disease)
• abnormal lung function leading to shortness of breath (respiratory failure)
• swelling and (or) fluid in the lungs (pulmonary edema)
• inflammation of the lung tissue (interstitial lung disease)
• abnormal lung image on X-ray (pulmonary infiltrates)
• bleeding from the lungs (pulmonary hemorrhage)
• oxygen absorption disorders in the lungs (hypoxia)
• raised skin rash (maculopapular rash)
• a disease that causes a decrease in bone density, weakening and fragility (osteoporosis)
• reaction at the injection site

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

• severe bone pain, chest pain, abdominal pain or joint pain (sickle cell anemia with crises)
• severe allergic reaction (anaphylactic reaction)
• pain and swelling of the joints resembling gout (pseudogout)
• disorders of fluid regulation in the body, which can cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin
• purple, raised, painful skin ulcers on the limbs, sometimes on the face and neck with accompanying fever (Sweet's syndrome)
• worsening of rheumatoid arthritis symptoms
• unusual changes in urine
• decreased bone mineral density
• inflammation of the aorta (a large blood vessel that carries blood from the heart to the rest of the body), see section 2
• production of blood cells outside the bone marrow (extramedullary hematopoiesis)

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, tell the doctor or nurse. Side effects can be reported directly to:
Department for Monitoring of Adverse Reactions to Medicinal Products, Medical Devices and Biocides
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Neupogen

Keep the medicine out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Store the pre-filled syringe in the outer cardboard box to protect it from light.
Accidental freezing does not affect the quality of the medicine.
Do not use this medicine after the expiry date stated on the label of the vial and carton after: Expiry date or EXP. The expiry date refers to the last day of the month stated.
Do not use this medicine if discoloration, cloudiness or particles are visible. The solution should be clear and colorless.
Medicines should not be disposed of via wastewater or household waste. Ask the pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and other information

What Neupogen contains

• The active substance of the medicine is filgrastim with a strength of 600 micrograms/ml (30 million IU/0.5 ml) or 960 micrograms/ml (48 million IU/0.5 ml).
• The other ingredients are: acetic acid, sodium hydroxide 1N, sorbitol (E420), polysorbate 80, water for injections.

What Neupogen looks like and what the package contains

Neupogen is a clear, colorless solution for injection (injection)/concentrate for solution for infusion (sterile concentrate) in a pre-filled syringe.
Neupogen is available in packs containing one pre-filled syringe.

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
To obtain more detailed information about this medicine, contact the local representative of the marketing authorization holder:

Poland

Amgen Biotechnology Sp. z o.o.
ul. Puławska 145
02-715 Warsaw
Phone: +48 22 581 3000
medinfo-pol@amgen.com

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 marketed under the name Granulokine.

Date of last revision of the leaflet: March 2024.

Other sources of information

Detailed information about this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocides (www.urpl.gov.pl/).
---------------------------------------------------------------------------------------------------------------------------

7. Instructions for injecting Neupogen

This section provides information on how to inject Neupogen.
Important:do not attempt to inject Neupogen yourself without prior training by your doctor or nursing staff.
Neupogen injection is administered into the tissue just under the skin. This method of administering medicines is called subcutaneous injection.

Equipment needed to administer the medicine

To inject Neupogen subcutaneously, you will need:

• a Neupogen pre-filled syringe,
• alcohol swabs or similar.

What to do before injecting Neupogen yourself

• 1. Remove one tray with a pre-filled syringe from the refrigerator and leave it at room temperature for about 30 minutes or hold it gently in your hand for a few minutes. This will make the injection less painful. Do notheat Neupogen in any other way (e.g., in a microwave or hot water).
• 2. Do not shake the pre-filled syringe.
• 3. Place the tray in your hand and tear off the paper part.
• 4. Turn the tray over and place the pre-filled syringe in your hand.
• 5. Do notremove the needle shield until everything is ready for injection.
• 6. Check the expiry date on the pre-filled syringe label (EXP). Do not use the medicine if the last day of the month stated on the label has passed.
• 7. Check the appearance of the medicine. Neupogen should be a clear and colorless liquid. Do not use the medicine if discoloration, cloudiness or particles are visible.
• 8.

Wash your hands carefully.

• 9. Gather the necessary items in a clean, easily accessible and well-lit place.

How to prepare the Neupogen injection

Before injecting Neupogen,:

• 1. To avoid bending the needle, grasp the glass cylinder of the pre-filled syringe safely; gently, without twisting, remove the needle shield, as shown in figures 1 and 2.
• 2. Do not touch the needle or press the plunger.
• 3. Small air bubbles may be visible in the pre-filled syringe. Removing these bubbles before injection is not necessary. Injecting a solution containing air bubbles is harmless.
• 4. The pre-filled syringe is now ready for use.

Where to inject Neupogen yourself

The best places to inject Neupogen yourself are the upper thighs and abdomen. If someone else is injecting, they can use the back of the arms.
You can change the injection site if the current site is red or painful.

How to inject Neupogen yourself

• 1. Disinfect the skin with an alcohol swab and grasp (but do not squeeze) the skin fold between your thumb and index finger.
• 2. Insert the needle fully into the skin, as shown by the nurse or doctor.
• 3. Push the plunger with steady pressure, still holding the skin fold between your fingers, and inject the medicine until the syringe is empty.
• 4. Remove the needle and release the skin fold.
• 5. If a drop of blood appears at the injection site, gently wipe it off with a swab or cotton ball. Do not rub the skin at the injection site. If necessary, a plaster can be applied to the injection site.
• 6. One syringe is for single use only. Do not use leftover Neupogen from the syringe.

Important:if you have any doubts, do not hesitate to contact your doctor or nursing staff for help.

Disposal of used syringes

• Do not replace the needle shield on used needles, as this may cause accidental puncture.
• Used syringes should be stored in a place that is inaccessible and invisible to children.
• Used syringes should not be disposed of in household waste. Ask the pharmacist what to do with used syringes or syringes that are no longer needed.

Information intended for healthcare professionals only:

When used as a concentrate for solution for infusion, Neupogen should be diluted in 20 ml of 5% glucose solution. Detailed information is available in the Summary of Product Characteristics.