GRANULOKINE 30 MU/0.3 MG/ML Roztwór

Treść ulotki

1. Granulokine 30 MU (0,3 mg/ml)
   1. What is Granulokine and what is it used for
   2. What you need to know before using Granulokine
   3. How to use Granulokine
   4. Possible side effects
   5. How to store Granulokine
   6. Package contents and other information
2. Granulokine 30 MU (0,6 mg/ml), 48 MU (0,96 mg/ml)
   1. What is Granulokine and what is it used for
   2. What you need to know before you use Granulokine
   3. How to use Granulokine
   4. Possible side effects
   5. How to store Granulokine
   6. Contents of the pack and other information
   7. Instructions for Granulokine injection

Granulokine 30 MU (0,3 mg/ml)

injectable solution
filgrastim
Read this leaflet carefully before you start to use this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4. Contents of this leaflet:
• 1. What Granulokine is and what it is used for
• 2. What you need to know before you use Granulokine
• 3. How to use Granulokine
• 4. Possible side effects
• 5. How to store Granulokine
• 6. Contents of the pack and other information

1. What is Granulokine and what is it used for

Granulokine is a white blood cell growth factor (granulocyte colony stimulating factor) and belongs to the group of medicines called cytokines. Growth factors are proteins produced naturally in the body, but can also be produced with the aid of biotechnology, to be used as medicines. Granulokine stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against infections. Granulokine stimulates the bone marrow to produce new white blood cells quickly.
Granulokine can be used:

• to increase the number of white blood cells after chemotherapy treatment, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections;
• before high-dose chemotherapy, to induce the bone marrow to produce more stem cells, which can be collected and re-infused into the patient after treatment. These cells can be taken from you 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 cases of severe chronic neutropenia, thus 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 Granulokine

Do not use Granulokine

• if you are allergic to filgrastim or any of the other ingredients of this medicine (listed in section 6). Warnings and precautionsTalk to your doctor, pharmacist or nurse before using Granulokine. Before starting treatment with Granulokine, tell your doctor if you have:
• sickle cell anemia, as Granulokine may cause sickle cell crises;
• osteoporosis (bone disease).

Tell your doctor immediately during treatment with Granulokine 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 or wheezing, as these may be signs of a severe allergic reaction (hypersensitivity).
• you experience facial or ankle swelling, blood in your urine or brown-colored urine, or notice that you are urinating less than usual (glomerulonephritis).
• you have pain in the upper left side of your abdomen (abdominal pain), pain under the left side of your rib cage, or at the tip of your left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or a possible rupture of the spleen).
• you notice unusual bleeding or the appearance of bruises (these may be symptoms of a decrease in the number of platelets (thrombocytopenia) with a reduced ability of the blood to clot).
• you have symptoms of inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy people. Symptoms may include fever, abdominal pain, malaise, back pain, and increased markers of inflammation. Tell your doctor if you experience such symptoms.

Loss of response to filgrastim
If you experience a disappearance of response or an inability to maintain a response to treatment
with filgrastim, your doctor will analyze the reasons, including the possible development of antibodies
that neutralize the activity of filgrastim.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a
blood cancer (leukemia, myelodysplastic syndrome (MDS)). You should consult your
doctor about your risk of developing blood cancers and what tests should be done.
If you develop or are likely to develop a blood cancer, you should not use
Granulokine, unless instructed by your doctor.
If you are a stem cell donor, your age must be between 16 and 60 years.

Pay particular attention to other products capable of stimulating white blood cells
Granulokine is part of a group of products that stimulate the production of white blood cells.
The healthcare professional must always record the exact product you are using.

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

Pregnancy and breastfeeding
Granulokine has not been tested in pregnant women or breastfeeding women.
Granulokine is not recommended during pregnancy.
It is important to tell your doctor if:

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

If you find out you are pregnant during treatment with Granulokine, tell your
doctor.
Unless your doctor tells you otherwise, you should stop breastfeeding if you use
Granulokine.

Driving and using machines
Granulokine may slightly impair your ability to drive vehicles and use machines. This
medicine may cause dizziness. It is recommended to wait and observe how you feel after
taking Granulokine, before driving vehicles or using machines.

Granulokine 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’.

Granulokine contains sorbitol
This medicine contains 50 mg of sorbitol per ml.
Sorbitol is a source of fructose. If your doctor has diagnosed you (or your child)
with hereditary fructose intolerance (HFI), a rare genetic disease, you (or your child) should not
take this medicine. Patients with hereditary fructose intolerance (HFI) are unable to
break down fructose, the build-up of which can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary
fructose intolerance (HFI) or if the child feels unwell, vomits or has unpleasant reactions such as
swelling and stomach cramps or diarrhea when consuming sweet foods or drinks.

3. How to use Granulokine

Use this medicine following the instructions of your doctor exactly. If you have any doubts
consult your doctor, nurse or pharmacist.

How Granulokine should be administered and how much should I take?
Granulokine is usually administered by daily injection into the tissue immediately
under the skin (subcutaneous injection). It can also be administered by slow
daily injection into a vein (intravenous infusion). As a rule, the usual dose varies
depending on your condition and your weight. Your doctor will tell you the amount of Granulokine that you must
take.
Patients receiving bone marrow transplant after chemotherapy:
You will normally receive the first dose of Granulokine at least 24 hours after chemotherapy and
at least 24 hours after bone marrow transplant.

How long should I take Granulokine?
You will need to take Granulokine until the number of white blood cells in your blood has
returned to normal. To monitor the number of white blood cells in your blood, you will undergo periodic
blood tests. Your doctor will tell you how long you will need to take Granulokine.

Use in children
Granulokine is used to treat children who are undergoing chemotherapy or who suffer from
a severe reduction in the number of white blood cells (neutropenia). The dosage in
children undergoing chemotherapy is the same as used in adults.

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

If you forget to use Granulokine
If you have forgotten an injection, contact your doctor as soon as possible.
If you have any doubts about 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 everyone gets them.

Tell your doctor immediatelyduring treatment:

• if you experience allergic reactions, including weakness, low blood pressure, difficulty breathing and swelling of the face (anaphylaxis), skin rashes and itchy skin (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients taking Granulokine. Tell your doctor immediately if you experience swelling of the face or ankles, blood in your urine, or brown-colored urine, or if you notice that you are urinating less than usual.
• if you experience any or a combination of the following side effects:
• swelling or edema, which may be associated with less frequent urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly. These may be symptoms of a condition called "capillary leak syndrome," which causes blood to leak from small blood vessels inside the body and requires urgent medical attention.
• if you experience a combination of the following symptoms:
• fever, chills, feeling very cold, rapid heartbeat, confusion or disorientation, shortness of breath, severe pain or discomfort, and moist, sweaty skin. These could be symptoms of a condition called "sepsis" (also called "blood poisoning"), a serious infection with inflammation throughout the body that can be life-threatening and requires urgent medical attention.
• if you experience pain in the upper left side (of the abdomen), pain under the left rib, or pain at the tip of the shoulder, as there may be 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 regularly check your urine if you experience this side effect or if protein is found in your urine (proteinuria). A common side effect with the use of Granulokine is muscle or bone pain (musculoskeletal pain) which can be relieved by taking common pain relievers (analgesics). In patients undergoing stem cell donation or bone marrow transplantation, graft-versus-host disease (GvHD) may occur - this is a reaction of the donor's cells against the person receiving the transplant; signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and sores in the mouth, intestines, liver, skin, or eyes, lungs, vagina, and joints. In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a decrease in the number of platelets (thrombocytopenia) may be observed, which lowers the blood's ability to clot; these will be monitored by your doctor. Very common side effects(may affect more than 1 in 10 people):
• reduction in platelets which lowers the blood's ability to clot (thrombocytopenia)
• reduction in red blood cells (anemia)
• headache
• diarrhea
• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue
• ulceration and swelling of the lining cells of the digestive tract, i.e. from the mouth to the anus (mucositis)
• fever (pyrexia)

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• loss of appetite
• difficulty sleeping (insomnia)
• dizziness
• decreased sensitivity, especially on the skin (hypoesthesia)
• tingling or numbness of 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)
• nosebleed (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• rash
• skin redness (erythema)
• muscle spasm
• pain when urinating (dysuria)
• chest pain
• pain
• general fatigue (asthenia)
• general feeling of discomfort (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in blood chemistry values
• transfusion reactions

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

• increased number of white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• rejection of bone marrow transplant (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of small veins inside the liver (veno-occlusive disease)
• inadequate lung function, causing shortness of breath (respiratory failure)
• fluid buildup and/or fluid in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial lung disease)
• abnormalities on a chest x-ray (pulmonary infiltrate)
• bleeding from the lungs (pulmonary hemorrhage)
• loss of oxygen absorption in the lung (hypoxia)
• irregular skin rashes (maculo-papular rash)
• disease that causes a decrease in bone density, making them weaker, more fragile and more likely to break (osteoporosis)
• reactions at the injection site

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

• severe bone, chest, intestinal or joint pain (sickle cell anemia with crisis)
• sudden, life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling in the joints, similar to gout (pseudogout)
• a change in the regulation of fluids in the body that can cause swelling (fluid volume disorders)
• inflammation of the blood vessels in the skin (cutaneous vasculitis)
• painful, raised, purple lesions on the limbs, sometimes also on the face and neck with fever (Sweet's syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• decreased bone density
• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see paragraph 2
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Granulokine

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 will not damage Granulokine.
Do not use this medicine after the expiry date which is stated on the vial label
(EXP) and on the box after Scad. The expiry date refers to the last day of that month.
Do not use this medicine if you notice abnormal coloration, turbidity or particles, it must be a
clear and colorless liquid.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist
how to eliminate medicines that you no longer use. This will help protect the environment.

6. Package contents and other information

What Granulokine contains

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

Description of the appearance of Granulokine and package contents
Granulokine is a clear and colourless injectable solution (injectable)/concentrate for solution
for infusion (sterile concentrate) in a vial.
Granulokine is available in packs of one vial. Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
Netherlands

Marketing authorisation 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

This medicinal product is authorised in the Member States of the European Economic Area and in the
United Kingdom (Northern Ireland) under the following denominations:
Neupogen, except in Cyprus, Greece and Italy where it is called Granulokine.
More detailed information on this medicine is available on the website of the Italian Medicines Agency (AIFA): https://www.aifa.gov.it/

Local representative of the marketing authorisation holder:
Amgen S.r.l.
Via Enrico Tazzoli, 6

• 20154 – Milan Tel.: 02-62.41.121

The following information is intended exclusively for doctors or healthcare professionals:
When used as a concentrate for solution for infusion, Granulokine must be diluted
in 20 ml of 5% glucose solution. Please see the Summary of Product Characteristics for more details.

Granulokine 30 MU (0,6 mg/ml), 48 MU (0,96 mg/ml)

injectable solution in a pre-filled syringe
filgrastim
Read this leaflet carefully before you start using this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4. Contents of this leaflet:
• 1. What Granulokine is and what it is used for
• 2. What you need to know before you use Granulokine
• 3. How to use Granulokine
• 4. Possible side effects
• 5. How to store Granulokine
• 6. Contents of the pack and other information
• 7. Instructions for injecting Granulokine

1. What is Granulokine and what is it used for

Granulokine is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to the group of medicines called cytokines. Growth factors are proteins produced naturally in the body, but can also be produced with the aid of biotechnology, to be used as medicines. Granulokine stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against infections. Granulokine stimulates the bone marrow to rapidly produce new white blood cells.
Granulokine can be used:

• to increase the number of white blood cells after chemotherapy treatment, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections;
• before high-dose chemotherapy, to induce the bone marrow to produce more stem cells, which can be collected and re-infused into the patient after treatment. These cells can be taken from you 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 cases of severe chronic neutropenia, thus helping to prevent infections;
• in patients with advanced HIV infection, to help reduce the risk of infections.

2. What you need to know before you use Granulokine

Do not use Granulokine

• if you are allergic to filgrastim or any of the other ingredients of this medicine (listed in section 6). Warnings and precautionsTalk to your doctor, pharmacist or nurse before using Granulokine. Before starting treatment with Granulokine, tell your doctor if you have:
• sickle cell anemia, as Granulokine may cause sickle cell crises.
• an allergy to natural rubber (latex). The needle cap of the syringe may be made of a type of natural rubber and may cause allergic reactions.
• osteoporosis (bone disease).

Tell your doctor immediately during treatment with Granulokine 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 or wheezing as these may be signs of a severe allergic reaction (hypersensitivity).
• you experience swelling of the face or ankles, blood in the urine or brown-colored urine, or notice that you are urinating less than usual (glomerulonephritis).
• you have pain in the upper left side of the abdomen (abdominal pain), pain under the left side of the rib cage or at the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or a possible rupture of the spleen).
• you notice unusual bleeding or bruising (these may be symptoms of a decrease in the number of platelets (thrombocytopenia) with a reduced ability of the blood to clot).
• you have symptoms of inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy people. Symptoms may include fever, abdominal pain, malaise, back pain and increased markers of inflammation. Tell your doctor if you experience such symptoms. Loss of response to filgrastimIf you experience a disappearance of response or an inability to maintain a response to treatment with filgrastim, your doctor will analyze the reasons, including the possible development of antibodies that neutralize the activity of filgrastim.

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 your doctor about your risk of developing blood cancer and what tests should be done. If you develop or are likely to develop blood cancer, you should not use Granulokine, unless instructed by your doctor. If you are a stem cell donor, your age must be between 16 and 60 years.

Pay particular attention to other products capable of stimulating white blood cells
Granulokine is part of a group of products that stimulate the production of white blood cells.
The healthcare professional must always record the exact product you are using.

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

Pregnancy and breastfeeding
Granulokine has not been tested in pregnant women or breastfeeding women.
Granulokine is not recommended during pregnancy.
It is important to tell your doctor if:

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

If you find out that you are pregnant during treatment with Granulokine, tell your doctor.
Unless your doctor tells you otherwise, you should stop breastfeeding if you use Granulokine.

Driving and using machines
Granulokine may slightly impair your ability to drive and use machines. This medicine may cause dizziness. It is recommended to wait and see how you feel after taking Granulokine, before driving or using machines.

Granulokine contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e.
essentially ‘sodium-free’.

Granulokine contains sorbitol
This medicine contains 50 mg of sorbitol per ml.
Sorbitol is a source of fructose. If your doctor has diagnosed you (or your child) with hereditary fructose intolerance (HFI), a rare genetic disease, you (or your child) should not take this medicine. Patients with hereditary fructose intolerance (HFI) are unable to break down fructose, the accumulation of which can cause serious side effects. Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary fructose intolerance (HFI) or if the child feels unwell, vomits or has unpleasant reactions such as bloating and stomach cramps or diarrhea when taking sweet foods or drinks.

4. How to use Granulokine

Use this medicine following the instructions of your doctor exactly. If you have any doubts
consult your doctor, nurse or pharmacist.

How should Granulokine be administered and how much should I take?
Granulokine is usually administered by daily injection into the tissue immediately
under the skin (subcutaneous injection). It can also be administered by slow
daily injection into a vein (intravenous infusion). As a rule, the usual dose varies
depending on your condition and your weight. Your doctor will tell you the amount of Granulokine that you must
take.
Patients receiving bone marrow transplant after chemotherapy:
You will normally receive the first dose of Granulokine at least 24 hours after chemotherapy and
at least 24 hours after bone marrow transplant.
You or the person assisting you may be trained to administer the injections
subcutaneously, so that you can continue your treatment at home. However, you should not
attempt to do this before receiving appropriate training from the healthcare
professional.

For how long should I take Granulokine?
You will need to take Granulokine until the number of white blood cells in your blood has
returned to normal. To monitor the number of white blood cells in your blood, you will undergo periodic
blood tests. Your doctor will tell you how long you will need to take Granulokine.

Use in children
Granulokine is used to treat children who are undergoing chemotherapy or who suffer from
a severe reduction in the number of white blood cells (neutropenia). The dosage in
children undergoing chemotherapy is the same as that used in adults.

If you use more Granulokinethan you should
Do not increase the dose prescribed by your doctor. If you think you have injected more than you should, contact your doctor as soon as possible.

If you forget to use Granulokine
If you have forgotten an injection or have injected too little medicine, contact your doctor
as soon as possible. Do not take a double dose to make up for a missed dose.
If you have any doubts about 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 everyone gets them.

Tell your doctor immediatelyduring treatment:

• if you experience allergic reactions, including weakness, low blood pressure, difficulty breathing and swelling of the face (anaphylaxis), skin rashes and itchy skin (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients taking Granulokine. Tell your doctor immediately if you experience swelling of the face or ankles, blood in your urine, or brown-colored urine, or if you notice that you are urinating less than usual.
• if you experience any or a combination of the following side effects:
• swelling or edema, which may be associated with less frequent urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly. These may be symptoms of a condition called "capillary leak syndrome", which causes blood to leak from small blood vessels inside the body and requires urgent medical attention.
• if you experience a combination of the following symptoms:
• fever, chills, feeling very cold, rapid heartbeat, confusion or disorientation, shortness of breath, severe pain or discomfort, and moist, sweaty skin. These may be symptoms of a condition called “sepsis” (also called “blood poisoning”), a serious infection with an inflammatory response throughout the body that can be life-threatening and requires urgent medical attention.
• if you experience pain in the upper left side (of the abdomen), pain under the left rib, or pain at the tip of the shoulder, as there may be a problem with the spleen (splenomegaly (enlarged spleen) or ruptured spleen).
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). Your doctor may regularly check your urine if you experience this side effect or if proteins are found in your urine (proteinuria). A common side effect with the use of Granulokine is muscle or bone pain (musculoskeletal pain) which can be relieved by taking common pain relievers (analgesics). In patients undergoing stem cell donation or bone marrow transplantation, graft-versus-host disease (GvHD) may occur - this is a reaction of the donor's cells against the person receiving the transplant; signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and sores in the mouth, intestines, liver, skin, or eyes, lungs, vagina, and joints. In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a decrease in the number of platelets (thrombocytopenia), which lowers the blood's ability to clot, may be observed; these will be monitored by the doctor.

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

• decreased platelets which lowers the blood's ability to clot (thrombocytopenia)
• decreased red blood cells (anemia)
• headache
• diarrhea
• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue
• ulceration and swelling of the cells lining the digestive tract, i.e. from mouth to anus (mucositis)
• fever (pyrexia)

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• loss of appetite
• sleep problems (insomnia)
• dizziness
• decreased sensitivity, especially on the skin (hypoesthesia)
• tingling or numbness of 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 (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• rash
• skin redness (erythema)
• muscle spasm
• pain when urinating (dysuria)
• chest pain
• pain
• general fatigue (asthenia)
• general feeling of discomfort (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in blood chemistry values
• transfusion reactions

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

• increased number of white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• rejection of bone marrow transplant (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of small veins inside the liver (veno-occlusive disease)
• inadequate lung function, causing shortness of breath (respiratory failure)
• fluid buildup and/or fluid in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial lung disease)
• abnormalities on chest x-ray (pulmonary infiltrate)
• bleeding from the lungs (pulmonary hemorrhage)
• loss of oxygen absorption in the lung (hypoxia)
• irregular skin rashes (maculo-papular rash)
• disease that causes a decrease in bone density, making them weaker, more fragile and more likely to break (osteoporosis)
• reactions at the injection site

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

• severe pain in the bones, chest, intestines or joints (sickle cell anemia with crisis)
• sudden, life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling in the joints, similar to gout (pseudogout)
• a change in the regulation of fluids in the body that can cause swelling (fluid volume disorders)
• inflammation of the blood vessels of the skin (cutaneous vasculitis)
• purple, raised and painful lesions on the limbs, sometimes also on the face and neck with fever (Sweet syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• decreased bone density
• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see paragraph 2
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Granulokine

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 will not damage Granulokine.
Do not use this medicine after the expiry date which is stated on the syringe label and
on the box after Exp. The expiry date refers to the last day of that month.
Do not use this medicine if you notice abnormal coloration, turbidity or particles; it must be a
clear and colorless liquid.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist
how to eliminate medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Granulokine contains

• The active substance is filgrastim 30 million units (0.6 mg/ml) or 48 million units (0.96 mg/ml).
• The excipients are sodium acetate, sorbitol (E420), polysorbate 80 and water for injections. Description of the appearance of Granulokine and contents of the packGranulokine is a clear and colourless injectable solution (injectable) / concentrate for infusion solution (sterile concentrate) in a pre-filled syringe. Granulokine is available in packs of one or five pre-filled syringes. Not all pack sizes may be marketed. Marketing Authorisation Holder and ManufacturerAmgen Europe B.V. Minervum 7061 4817 ZK Breda Netherlands Marketing Authorisation HolderAmgen Europe B.V. Minervum 7061 4817 ZK Breda Netherlands ManufacturerAmgen Technology (Ireland) Unlimited Company Pottery Road Dun Laoghaire Co Dublin Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

This medicinal product is authorised in the Member States of the European Economic Area and in the
United Kingdom (Northern Ireland) under the following denominations:
Neupogen, with the exception of Cyprus, Greece and Italy where it is called Granulokine.
More detailed information on this medicine is available on the website of the
Italian Medicines Agency (AIFA): https://www.aifa.gov.it/

7. Instructions for Granulokine injection

This paragraph contains information on how to administer a Granulokine injection.

Important:do not attempt to administer a Granulokine injection unless you have been shown how to do so by your doctor or nurse.
Granulokine is administered into the tissue immediately beneath the skin. This is known as a
subcutaneous injection.

What you need
To give yourself a subcutaneous injection you will need:

• a new pre-filled syringe of Granulokine; and
• cotton balls soaked in alcohol or similar disinfectants.

What should I do before giving myself a subcutaneous Granulokine injection?

• 1. Remove a blister containing a 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 more comfortable. Do notheat Granulokine in any other way (for example in a microwave oven or in hot water).
• 2. Do not shake the pre-filled syringe.
• 3. Place the blister in your hand and remove the paper from the blister.
• 4. Discard the blister to place the pre-filled syringe in your palm.
• 5. Do notremove the cap from the needle until you are ready to give the injection.
• 6. Check the expiry date on the label of the pre-filled syringe after (EXP). Do not use it if the last day of the month indicated has passed.
• 7. Check the appearance of Granulokine. It should be a clear and colourless liquid. If there is abnormal coloration, if it is cloudy or if particles are visible, do not use it.
• 8. Wash your hands thoroughly.
• 9. Find a comfortable, well-lit and clean surface and keep everything you need close at hand.

How do I prepare the Granulokine injection?

Before giving yourself a Granulokine injection, you must perform the
following operations:

• 1. To avoid bending the needle, securely hold the pre-filled syringe by the central glass part. Gently remove the cap from the needle, without rotating it, as shown in figures 1 and 2.
• 2. Do not touch the needle or push the plunger.
• 3. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before giving the injection. Injecting the solution with the air bubble is harmless.
• 4. You can now use the pre-filled syringe.

Where should I give myself the injection?

The most suitable places to give yourself an injection are the upper thighs and the abdomen. If someone else is giving you the injection, they can also use the back of your arms.
You should change the injection site if you notice that the area is red or sore.

How do I give the injection?

• 1. Disinfect the skin using the alcohol-soaked cotton ball and lift the skin between your thumb and index finger without pinching it.
• 2. Insert the needle completely into the skin as shown to you by the nurse or doctor.
• 3. Push the plunger with a slow and steady pressure, keeping the skin lifted, until the syringe is empty.
• 4. Remove the needle and release the skin.
• 5. If you notice a small drop of blood, remove it gently with a cotton ball or gauze. Do not rub the injection site. If necessary, you can cover the injection site with an adhesive bandage.
• 6. Use each syringe for only one injection. Do not reuse any Granulokine remaining in the syringe.

Remember:if you have problems, do not hesitate to consult your doctor or nurse for help or
advice.

Disposal of used syringes

• Do not replace the cap on used needles, as you may accidentally prick yourself.
• Keep used syringes out of the reach and sight of children.
• Used syringes must not be thrown into the normal household waste bin. Your pharmacist will know how to dispose of used syringes or syringes that are no longer used.

Local representative of the marketing authorisation holder:
Amgen S.r.l.
Via Enrico Tazzoli, 6

• 20154 – Milano Tel.: 02-62.41.121

The following information is intended exclusively for doctors or healthcare professionals:
When used as a concentrate for infusion solution, Granulokine must be diluted
in 20 ml of 5% glucose solution. Please see the Summary of Product Characteristics for more details.