Package leaflet: Information for the user

Granulokine 30 MU (0.3 mg/ml)

injection solution
filgrastim
Please read all of this leaflet carefully before you start using this medicine because 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 give it to other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Granulokine is and what it is used for
What you need to know before using Granulokine
How to use Granulokine
Possible side effects
How to store Granulokine
Contents of the pack and other information

1. What Granulokine is and what it is used for

Granulokine is a growth factor for white blood cells (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins naturally produced in the body, but they can also be produced using biotechnology for use 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) may 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 may be used:

to increase the number of white blood cells after chemotherapy treatment, thereby helping to prevent infections;
to increase the number of white blood cells after a bone marrow transplant, thereby helping to prevent infections;
prior to high-dose chemotherapy, to stimulate the bone marrow to produce more stem cells, which can be collected and reinfused into the patient after treatment. These cells may be collected 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, thereby 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 to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Granulokine.
Before starting treatment with Granulokine, inform your doctor if you have:

sickle cell disease, as Granulokine may cause sickle cell crises;
osteoporosis (a bone disease).

Immediately inform your doctor during treatment with Granulokine if:

you experience sudden signs of allergy, such as rash, itching, hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath or difficulty breathing, as these may be signs of a severe allergic reaction (hypersensitivity);
you develop swelling of the face or ankles, blood in the urine, brown-colored urine, or notice that you are urinating less than usual (glomerulonephritis);
you have pain in the upper left part of the abdomen, pain under the left side of the rib cage, or pain at the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or possible spleen rupture);
you notice unusual bleeding or bruising (these may be symptoms of a low platelet count (thrombocytopenia), resulting in reduced blood clotting ability);
you experience symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Inform your doctor if you experience any of these symptoms.

Loss of response to filgrastim
If you experience a loss of response or inability to maintain a response to treatment with filgrastim, your doctor will investigate possible causes, including the potential development of antibodies that neutralize the activity of filgrastim.
Your doctor may wish to monitor you closely; see section 4 of the package leaflet.
If you are a patient with severe chronic neutropenia, you may be at risk of developing blood cancer (leukemia, myelodysplastic syndrome (MDS)). You should discuss with your doctor your risk of developing blood cancers and which tests should be performed.
If you have developed or are at risk of developing blood cancer, you must not use Granulokine except under the direction of your doctor.
If you are a stem cell donor, your age must be between 16 and 60 years.
Pay special attention to other products that stimulate white blood cells
Granulokine belongs to a group of products that stimulate the production of white blood cells. Healthcare professionals must always record the exact product you are using.

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

Pregnancy and breastfeeding
Granulokine has not been studied in pregnant or breastfeeding women.
Granulokine is not recommended during pregnancy.
It is important that you inform your doctor if:

you are pregnant or breastfeeding;
you suspect you might be pregnant; or
you are planning a pregnancy.

If you find out you are pregnant while being treated with Granulokine, inform your doctor.
Unless otherwise instructed by your doctor, you must stop breastfeeding while using Granulokine.

Driving and using machines
Granulokine may have a minor influence on the ability to drive and use machines. This medicine may cause dizziness. It is recommended to wait and observe how you feel after taking Granulokine before driving or operating machinery.

Granulokine contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 0.3 mg/ml vial, 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 disorder, you (or your child) must not take this medicine. Patients with hereditary fructose intolerance (HFI) are unable to metabolize fructose, and its accumulation can lead to serious side effects.
Before taking this medicine, inform your doctor if you (or your child) have hereditary fructose intolerance (HFI) or if your child feels unwell, vomits, or experiences unpleasant reactions such as bloating, stomach cramps, or diarrhea after consuming sweet foods or drinks.

3. How to use Granulokine

Use this medicine exactly as instructed by your doctor. 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 as a daily injection into the tissue just beneath the skin (subcutaneous injection). It may also be given as a daily slow injection into a vein (intravenous infusion). The usual dose will depend on your condition and body weight. Your doctor will tell you how much Granulokine you should take.
Patients receiving bone marrow transplantation after chemotherapy:
You will normally receive your first dose of Granulokine at least 24 hours after chemotherapy and at least 24 hours after bone marrow transplantation.
How long should I take Granulokine?
You will need to take Granulokine until your white blood cell count has returned to normal. To monitor your white blood cell count, you will have regular blood tests. Your doctor will tell you how long you should continue taking Granulokine.
Use in children
Granulokine is used to treat children undergoing chemotherapy or suffering from severe reduction in white blood cells (neutropenia). The dosage in children undergoing chemotherapy is the same as that used in adults.
If you use more Granulokine than you should
If you think you have injected more than the prescribed amount, contact your doctor as soon as possible.
If you forget to use Granulokine
If you have missed an injection, contact your doctor as soon as possible.
If you have any questions 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 everybody gets them.
Contact your doctor immediately during treatment:

if you experience allergic reactions, including weakness, drop in blood pressure, breathing difficulties and facial swelling (anaphylaxis), skin rashes and episodes of itching (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnea).
if you experience cough, fever and breathing difficulties (dyspnea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
if you develop kidney damage (glomerulonephritis). Kidney damage has been observed in patients taking Granulokine. Contact your doctor immediately if you experience swelling of the face or ankles, blood in the urine or brown-colored urine, or if you notice that you are urinating less than usual.
if you experience one or a combination of the following side effects:
- swelling or puffiness, which may be associated with reduced urination, breathing difficulties, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly. They may be signs of a condition called "capillary leak syndrome", which causes fluid and blood to leak from small blood vessels into body tissues and requires urgent medical treatment.
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 known as “blood poisoning”), a serious infection with a systemic inflammatory response that can be life-threatening and requires urgent medical treatment.
if you experience pain in the upper left part of the abdomen, pain under the left rib or pain at the tip of the shoulder, as this may indicate a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).
if you are being treated for chronic severe 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 painkillers (analgesics). In patients undergoing stem cell donation or bone marrow transplantation, graft-versus-host disease (GvHD) may occur – this is a reaction of donor cells against the recipient; signs and symptoms include rash on the palms of the hands or soles of the feet, and ulcers or sores in the mouth, intestine, liver, skin, eyes, lungs, vagina or joints.
In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a reduction in platelet count (thrombocytopenia), which reduces 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):

reduction in platelets, which reduces the blood's ability to clot (thrombocytopenia)
reduction in red blood cells (anemia)
headache
diarrhea
vomiting
nausea
unusual hair loss or thinning (alopecia)
tiredness (fatigue)
ulceration and swelling of the mucosal lining of the digestive tract, from mouth to anus (mucositis)
fever (pyrexia)

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

inflammation of the lungs (bronchitis)
upper respiratory tract infection
urinary tract infection
decreased appetite
sleep problems (insomnia)
dizziness
reduced sensation, especially in the skin (hypoesthesia)
tingling or numbness in hands or feet (paresthesia)
low blood pressure (hypotension)
high blood pressure (hypertension)
cough
coughing up blood (hemoptysis)
pain in mouth and throat (oropharyngeal pain)
nosebleed (epistaxis)
constipation
oral pain
enlarged liver (hepatomegaly)
rash
redness of the skin (erythema)
muscle spasms
pain when urinating (dysuria)
chest pain
pain
general tiredness (asthenia)
general feeling of being unwell (malaise)
swelling of hands and feet (peripheral edema)
increase in certain liver enzymes in the blood
changes in blood chemistry values
transfusion reactions

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

increase in 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 may cause gout (hyperuricemia) (increased uric acid in blood)
liver damage caused by blockage of small veins within the liver (veno-occlusive disease)
impaired lung function causing breathlessness (respiratory failure)
swelling 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)
reduced oxygen uptake in the lungs (hypoxia)
irregular skin rashes (maculopapular rash)
disease causing reduced bone density, making bones weaker, more fragile and more likely to fracture (osteoporosis)
injection site reactions

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)
joint pain and swelling, similar to gout (pseudogout)
a disturbance in the body's fluid regulation that may cause swelling (fluid volume disorders)
inflammation of blood vessels in the skin (cutaneous vasculitis)
painful, raised purple lesions on limbs, sometimes also on face and neck, accompanied by fever (Sweet’s syndrome)
worsening of rheumatoid arthritis
unusual changes in urine
decreased bone density
inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
formation of blood cells outside the bone marrow (extramedullary hematopoiesis)

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

5. How to store Granulokine

Keep this medicine out of sight and reach of children.
Store in the 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 stated on the vial label (EXP) and on the carton after Exp. The expiry date refers to the last day of that month.
Do not use this medicine if you notice abnormal colouration, cloudiness or particles; it should be a clear, colourless liquid.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Granulokine contains

The active substance is filgrastim 30 million units in a 1 ml vial (0.3 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 pack
Granulokine is a clear, colourless solution for injection (injection)/sterile concentrate for solution for infusion 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
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Co Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Neupogen, except in Cyprus, Greece and Italy where it is called Granulokine.
More detailed information on this medicinal product 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 Luisa Battistotti Sassi, 1120133 – Milan
Tel.: 02-62.41.121

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

Package leaflet: information for the user

Granulokine 30 MU (0.6 mg/ml), 48 MU (0.96 mg/ml)

injectable solution in a pre-filled syringe
filgrastim
Please read this leaflet carefully before using this medicine because 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 give it to others, even if they have the same symptoms as you, because it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Granulokine is and what it is used for
What you need to know before using Granulokine
How to use Granulokine
Possible side effects
How to store Granulokine
Contents of the pack and other information
Instructions for injecting Granulokine

1. What Granulokine is and what it is used for

Granulokine is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins naturally produced in the body, but they can also be manufactured using biotechnology for use as medicines. Granulokine stimulates the bone marrow to produce a greater number of white blood cells.

A reduced number of white blood cells (neutropenia) may 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 may be used:

to increase the number of white blood cells after chemotherapy treatment, thereby helping to prevent infections;
to increase the number of white blood cells after a bone marrow transplant, thereby helping to prevent infections;
prior to high-dose chemotherapy, to stimulate the bone marrow to produce more stem cells, which can be collected and reinfused into the patient after treatment. These cells may be collected 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, thereby 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 to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Granulokine.
Before starting treatment with Granulokine, inform 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 natural rubber and may cause allergic reactions.
osteoporosis (a bone disease).

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

Loss of response to filgrastim
If you experience a loss of response or inability to maintain a response to treatment with filgrastim, your doctor will investigate possible reasons, including the potential development of antibodies that neutralize the activity of filgrastim.
Your doctor may wish to monitor you closely; see section 4 of the package leaflet.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a blood cancer (leukemia, myelodysplastic syndrome (MDS)). You should discuss with your doctor your risk of developing blood cancers and which tests should be performed.
If you have developed or are at risk of developing a blood cancer, you must not use Granulokine except on the advice of your doctor.
If you are a stem cell donor, your age must be between 16 and 60 years.
Pay special attention to other products that stimulate white blood cells
Granulokine belongs to a group of products that stimulate the production of white blood cells. Healthcare professionals must always record the exact product you are using.

Other medicines and Granulokine
Inform 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 or breastfeeding women.
Granulokine is not recommended during pregnancy.
It is important that you inform your doctor if:

you are pregnant or breastfeeding;
you suspect you may be pregnant; or
you are planning a pregnancy.

If you find out you are pregnant while being treated with Granulokine, inform your doctor.
Unless your doctor tells you otherwise, you must stop breastfeeding if you are using Granulokine.

Driving and using machines
Granulokine may have a minor effect on the ability to drive and use machines. This medicine may cause dizziness. You are advised to wait and observe how you feel after taking Granulokine before driving or operating machinery.

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 disorder, you (or your child) must not take this medicine. Patients with hereditary fructose intolerance (HFI) are unable to metabolize fructose, and its accumulation may cause serious side effects.
Before taking this medicine, inform your doctor if you (or your child) have hereditary fructose intolerance (HFI) or if your child feels unwell, vomits, or has unpleasant reactions such as bloating, stomach cramps, or diarrhea after consuming sweet foods or drinks.

4. How to use Granulokine

Use this medicine exactly as instructed by your doctor. 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 given as a daily injection into the tissue just beneath the skin (subcutaneous injection).
It may also be administered as a slow daily injection into a vein (intravenous infusion). The usual dose typically
depends on your condition and body weight. Your doctor will tell you how much Granulokine you should take.
Patients receiving bone marrow transplantation after chemotherapy:
You will normally receive your first dose of Granulokine at least 24 hours after chemotherapy and
at least 24 hours after bone marrow transplantation.
You or your caregiver may be trained to administer the subcutaneous injections so that you can continue
treatment at home. However, you must not attempt to do this before receiving proper training from a healthcare professional.
How long should I take Granulokine?
You will need to take Granulokine until your white blood cell count has returned to normal. To monitor your white blood cell count,
you will have periodic blood tests. Your doctor will tell you how long you should continue taking Granulokine.
Use in children
Granulokine is used to treat children undergoing chemotherapy or suffering from severe reduction in white blood cells (neutropenia).
The dosage in children undergoing chemotherapy is the same as that used in adults.
If you use more Granulokine than you should
Do not increase the dose prescribed by your doctor. If you think you have injected more than you should have, contact your doctor as soon as possible.
If you forget to use Granulokine
If you have missed an injection or injected too little medicine, contact your doctor as soon as possible.
Do not take a double dose to make up for a forgotten dose.
If you have any questions about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately during treatment:

if you experience allergic reactions, including weakness, drop in blood pressure, difficulty breathing, and swelling of the face (anaphylaxis), skin rash and episodes of itching (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnea).
if you experience cough, fever, and breathing difficulties (dyspnea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
if you develop kidney damage (glomerulonephritis). Kidney damage has been observed in patients taking Granulokine. Inform your doctor immediately if you experience swelling of the face or ankles, blood in the urine, brown-colored urine, or if you notice that you are urinating less than usual.
if you experience one or a combination of the following side effects:
- swelling or edema, which may be associated with reduced urination, difficulty breathing, abdominal swelling and feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly. They may indicate a condition called "capillary leak syndrome," which causes leakage of fluid from small blood vessels into body tissues and requires urgent medical treatment.
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 known as "blood poisoning"), a serious infection with a systemic inflammatory response that can be life-threatening and requires urgent medical treatment.
if you experience pain in the upper left part of the abdomen, pain under the left rib cage, or pain at the tip of the shoulder, as this may indicate a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).
if you are being treated for chronic severe 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 pain in the muscles or bones (musculoskeletal pain), which can be relieved by taking common painkillers (analgesics). In patients undergoing stem cell donation or bone marrow transplantation, graft-versus-host disease (GvHD) may occur – this is a reaction of donor cells against the recipient; 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, eyes, lungs, vagina, joints.

In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a reduction in platelet count (thrombocytopenia), which reduces 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):

reduction in platelets, reducing the blood’s ability to clot (thrombocytopenia)
reduction in red blood cells (anemia)
headache
diarrhea
vomiting
nausea
unusual hair loss or thinning (alopecia)
tiredness (fatigue)
ulceration and swelling of the lining cells of the digestive tract, from mouth to anus (mucositis)
fever (pyrexia)

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

inflammation of the lungs (bronchitis)
upper respiratory tract infection
urinary tract infection
decreased appetite
sleep problems (insomnia)
dizziness
reduced sensation, especially in the skin (hypoesthesia)
tingling or numbness in hands or feet (paresthesia)
low blood pressure (hypotension)
high blood pressure (hypertension)
cough
coughing up blood (hemoptysis)
mouth and throat pain (oropharyngeal pain)
nosebleed (epistaxis)
constipation
oral pain
enlarged liver (hepatomegaly)
rash
redness of the skin (erythema)
muscle spasm
pain when urinating (dysuria)
chest pain
pain
general tiredness (asthenia)
general feeling of discomfort (malaise)
swelling of hands and feet (peripheral edema)
increase in certain enzymes in the blood
changes in blood chemistry values
transfusion reactions

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

increase in 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 may cause gout (hyperuricemia) (increased uric acid in the blood)
liver damage caused by blockage of small veins within the liver (veno-occlusive disease)
inadequate lung function causing breathlessness (respiratory failure)
swelling 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 uptake in the lungs (hypoxia)
irregular skin rashes (maculopapular rash)
disease causing decreased bone density, making bones weaker, more fragile and more likely to break (osteoporosis)
injection site reactions

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)
joint pain and swelling, similar to gout (pseudogout)
a change in fluid regulation in the body that may cause swelling (fluid volume disorders)
inflammation of blood vessels in the skin (cutaneous vasculitis)
painful, raised purple lesions on limbs, sometimes also on face and neck with fever (Sweet’s syndrome)
worsening of rheumatoid arthritis
uncommon changes in urine
decreased bone density
inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via 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 the 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 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 colouration, turbidity, or particles; it should be a clear, colourless liquid.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents 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 pack
Granulokine is a clear, colourless injectable solution (injectable)/sterile concentrate for infusion solution 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
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands
Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands
Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Co Dublin
Ireland
Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium
This medicinal product is authorised in the Member States of the European Economic Area and in
the United Kingdom (Northern Ireland) under the following names:
Neupogen, except in Cyprus, Greece and Italy where it is called Granulokine.
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (AIFA): https://www.aifa.gov.it/

7. Instructions for the injection of Granulokine

This section contains information on how to administer a Granulokine injection.
Important: Do not attempt to inject Granulokine yourself unless you have been shown how to do so by your doctor or nurse.
Granulokine is administered into the tissue just 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 injection of Granulokine?

Remove a blister pack containing a syringe from the refrigerator and allow it to reach 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 not heat Granulokine in any other way (e.g., in a microwave or in warm water).
Do not shake the pre-filled syringe.
Place the blister pack in your hand and remove the paper from the blister.
Discard the blister and place the pre-filled syringe in the palm of your hand.
Do not remove the needle cap until you are ready to administer the injection.
Check the expiry date on the label of the pre-filled syringe (EXP). Do not use it if the date printed has passed.
Check the appearance of Granulokine. It should be a clear, colourless liquid. Do not use if it is discoloured, cloudy, or if particles are visible.
Wash your hands thoroughly.
Find a clean, well-lit, comfortable surface and have everything you need within reach.

How do I prepare the Granulokine injection?

Two diagrams show two hands separating or joining components of a medical device with directional arrows and an exposed needle

Before administering the Granulokine injection, you must perform the following steps:

To avoid bending the needle, hold the pre-filled syringe securely by the middle glass section. Gently remove the needle cap without twisting, as shown in figures 1 and 2.
Do not touch the needle or push the plunger.
You may notice a small air bubble in the pre-filled syringe. Do not remove the air bubble before administering the injection. Injecting the solution with the air bubble is harmless.
The pre-filled syringe is now ready for use.

Where should I give myself the injection?

Stylized diagram of a human body highlighting with gray areas the region

The most suitable sites for self-injection are the upper thighs and the abdomen. If someone else is giving you the injection, the back of the upper arms may also be used.
You should change the injection site if you notice redness or tenderness in the area.

How should I give the injection?

Clean the skin with an alcohol-soaked cotton ball and gently lift the skin between your thumb and index finger without squeezing it.
Insert the needle completely into the skin as demonstrated by your nurse or doctor.
Push the plunger slowly and steadily, keeping the skin lifted, until the syringe is empty.
Remove the needle and release the skin.
If you see a small drop of blood, gently wipe it away with a cotton ball or gauze. Do not rub the injection site. If needed, you may cover the injection site with an adhesive bandage.
Use each syringe for only one injection. Do not reuse any remaining Granulokine in the syringe.

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

Disposal of used syringes

Do not recap 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 regular household waste bins. Your pharmacist will advise you on the proper disposal of used or unused syringes.

Local representative of the Marketing Authorization Holder:
Amgen S.r.l.
Via Luisa Battistotti Sassi, 1120133 – Milan
Tel.: 02-62.41.121

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