Neupogen

Patient Information Leaflet

Neupogen, 300 micrograms/ml (30 million IU/ml), solution for injection
filgrastim
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm other people, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Neupogen is and what it is used for
2. Important information before using Neupogen
3. How to use Neupogen
4. Possible side effects
5. How to store Neupogen
6. Contents of the pack and other information

1. What Neupogen is and what it is 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 naturally produced in the body, which can be manufactured using biotechnological methods and used as medicines. Neupogen stimulates the bone marrow to produce more white blood cells.
A decrease in the number of white blood cells (neutropenia) may occur for several reasons. Neutropenia reduces the body's ability to fight infections. Neupogen stimulates the bone marrow to rapidly produce new white blood cells.
Neupogen may 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;
• prior to high-dose chemotherapy, to stimulate the bone marrow to produce a greater number of stem cells, which can be collected from the patient and later reinfused after completion of treatment. Stem cells may be collected from the patient himself/herself or from a donor. The transplanted stem cells return to the bone marrow and produce blood cells;
• to increase the number of white blood cells in patients 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 this with your doctor, pharmacist or
nurse.
Before starting treatment, inform your doctor if the patient has:

• sickle cell anaemia; Neupogen may cause a worsening of the disease.
• osteoporosis (a bone disorder).

Immediately tell your doctor if, during treatment with Neupogen, the patient experiences:

• sudden signs of hypersensitivity such as: rash, itching 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 appearing brown, or urine output less than usual (glomerulonephritis),
• pain in the upper left part of the abdomen, pain on the left side under the ribs, or pain at the top of the left shoulder [these may be symptoms of an enlarged spleen (splenomegaly) or possibly rupture of the spleen],
• unusual bleeding or bruising [these may be symptoms of reduced platelet count (thrombocytopenia) and reduced blood clotting ability],
• in patients with cancer and in healthy donors, symptoms of aortic inflammation (the large blood vessel carrying blood from the heart to the rest of the body) have been rarely observed. Symptoms may include: fever, abdominal pain, malaise, back pain and increased inflammatory markers. If the patient experiences such symptoms, inform the doctor immediately.

Loss of response to filgrastim
If the patient experiences a loss of response or inability to maintain response to filgrastim treatment, the doctor will investigate the reasons, including possible development of neutralising antibodies against 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 cancers [leukaemia, myelodysplastic syndrome (MDS)]. Discuss with the doctor the risk of developing blood cancers and which tests should be performed. If the patient develops blood cancers or there is a likelihood of their occurrence, Neupogen should not be used unless otherwise directed by the doctor.
Stem cell donors must be between 16 and 60 years of age.
Exercise particular caution when using other white blood cell stimulating products
Neupogen belongs to a group of medicines that stimulate the production of white blood cells. The treating doctor should always clearly record the brand name of the medicine administered to the patient.

Neupogen and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Pregnancy and breastfeeding
Studies with Neupogen have not been conducted in pregnant or breastfeeding women.
Use of Neupogen during pregnancy is not recommended.
It is important to inform the doctor:

• if the patient is pregnant or breastfeeding,
• if she suspects she may be pregnant, or
• if she is planning to have a child.

If the patient becomes pregnant while using Neupogen, she should inform her doctor.
Unless otherwise advised by the doctor, breastfeeding should be discontinued during treatment with Neupogen.

Driving and operating machinery
Neupogen may have a minor influence on the ability to drive and operate machinery. This medicine may cause dizziness. It is recommended that the patient waits and observes how they feel after taking Neupogen before driving or operating machinery.

Neupogen contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per 0.3 mg/ml vial, meaning the medicine is considered "sodium-free".

Neupogen contains sorbitol
The medicine contains 50 mg of sorbitol per ml.
Sorbitol is a source of fructose. If the patient has previously been diagnosed with hereditary fructose intolerance, a rare genetic disorder, the patient must not take this medicine. In patients with hereditary fructose intolerance, the body cannot break down the fructose contained in this medicine, which may lead to severe adverse reactions.
Inform the doctor before taking this medicine if the patient has hereditary fructose intolerance or if the patient cannot consume sweet foods or drinks for longer periods due to nausea, vomiting or unpleasant adverse effects such as bloating, stomach cramps or diarrhoea.

3. How to use Neupogen

This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult
the doctor, nurse, or pharmacist.
How Neupogen is administered and what is the dose
Neupogen is usually administered daily by injection into the tissue just under the skin
(subcutaneous injection). The medicine may also be given daily by slow injection into a vein
(intravenous infusion). The dose depends on the type of condition and the patient's body weight.
The doctor will inform the patient of the dose to be administered.
Patients undergoing bone marrow transplantation after chemotherapy:
The first dose of Neupogen is usually given at least 24 hours after chemotherapy
or at least 24 hours after bone marrow transplantation.
How long to use Neupogen
Neupogen should be used until the white blood cell count returns to normal. Blood tests will be
performed regularly to monitor the white blood cell count. The doctor will inform the patient
how long Neupogen should be used.
Use in children
Neupogen is used in children receiving chemotherapy or suffering from severe neutropenia
(a significant decrease in white blood cells). The dosing in children receiving chemotherapy
is the same as in adults.
Use of a higher than recommended dose of Neupogen
If a dose higher than recommended is suspected, contact the doctor immediately.
Missed dose of Neupogen
If a dose is missed, inform the doctor as soon as possible.
If there are any further doubts concerning the use of this medicine, consult the doctor, nurse, or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should immediately inform your doctor if, during treatment:

• an allergic reaction occurs, including weakness, sudden drop in blood pressure, breathing difficulties, facial swelling (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnoea).
• cough, fever, and breathing problems (dyspnoea) occur, as these may be symptoms of acute respiratory distress syndrome.
• kidney damage occurs (glomerulonephritis). Kidney damage has been observed in patients receiving Neupogen. Immediate contact with a doctor is necessary if the patient develops facial or ankle swelling, blood in the urine, or urine is darker than usual or passed in smaller amounts than normal.
• any of the following adverse reactions occur, either individually or in combination:
  • swelling or puffiness, which may be associated with reduced urination, difficulty breathing, abdominal swelling or feeling of fullness, and general fatigue. These symptoms usually develop rapidly. They may indicate a condition called "capillary leak syndrome," which causes blood to leak from small blood vessels into the patient's body and requires immediate medical intervention.
• any combination of the following symptoms occurs:
  • fever or chills or feeling intensely cold, rapid heartbeat, confusion, disorientation, shortness of breath, severe pain or discomfort, and cold, clammy or moist skin. These may be symptoms of a condition called "sepsis" (also known as blood poisoning), a serious infection leading to systemic inflammation, which may be life-threatening and requires immediate medical attention.
• pain occurs in the upper left part of the abdomen, pain on the left side under the ribs, or pain at the top of the shoulder, as these may indicate spleen disorders [enlargement of the spleen (splenomegaly) or rupture of the spleen].
• blood appears in the urine in severe chronic neutropenia. The doctor may recommend regular urine testing if this adverse reaction occurs or if protein is present in the urine (proteinuria).

A common adverse reaction following administration of Neupogen is muscle or bone pain (musculoskeletal pain), which can usually be relieved with commonly used painkillers. In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease may occur—this is a reaction of donor cells against the recipient's body; symptoms and signs of this disease include rash on the palms of the hands or soles of the feet, and ulcers and pain in the mouth, intestines, liver, skin, eyes, lungs, vagina, or joints.
In healthy stem cell donors, increased white blood cell count (leukocytosis) and decreased platelet count, leading to impaired blood clotting (thrombocytopenia), have been observed; these will be monitored by the doctor.

Very common adverse reactions (may affect more than 1 in 10 people):

• decreased platelet count, reducing blood clotting ability (thrombocytopenia)
• decreased red blood cell count (anaemia)
• headache
• diarrhoea
• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue
• pain and inflammation of the mucous membrane from the mouth to the anus (mucositis)
• fever

Common adverse reactions (may affect up to 1 in 10 people):

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• decreased appetite
• sleep disturbances (insomnia)
• dizziness
• reduced sensation, especially in the skin (hypoesthesia)
• tingling or numbness in hands or feet (paraesthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (haemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleeds
• constipation
• pain in the mouth
• enlarged liver (hepatomegaly)
• rash
• skin redness (erythema)
• muscle cramps
• pain during urination (dysuria)
• chest pain
• pain-related complaints
• general weakness (asthenia)
• general malaise
• swelling of hands and feet (peripheral oedema)
• increased activity of certain enzymes in the blood
• changes in blood biochemical test results
• transfusion reaction

Uncommon adverse reactions (may affect up to 1 in 100 people):

• increased white blood cell count (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 (hyperuricaemia) (increased uric acid levels in 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)
• lung swelling and/or fluid accumulation in the lungs (pulmonary oedema)
• inflammation of lung tissue (interstitial lung disease)
• abnormal lung X-ray findings (lung infiltrate)
• bleeding from the lungs (pulmonary haemorrhage)
• impaired oxygen uptake in the lungs (hypoxia)
• raised skin rash (maculopapular rash)
• disease causing reduced bone density, weakening, fragility, and increased risk of fractures (osteoporosis)
• injection site reaction

Rare adverse reactions (may affect up to 1 in 1000 people):

• severe bone, chest, intestinal, or joint pain (sickle cell anaemia with crisis)
• sudden, life-threatening allergic reaction (anaphylactic reaction)
• joint pain and swelling resembling gout (pseudogout)
• change in the body's fluid regulation, possibly leading to oedema (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• purple, raised, painful skin ulcers on limbs, sometimes on the face and neck, accompanied by fever (Sweet's syndrome)
• worsening of symptoms of rheumatoid arthritis
• unusual changes in urine
• decreased bone mineral density
• inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
• blood cell formation outside the bone marrow (extramedullary haematopoiesis)

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor or nurse. Adverse reactions can be reported directly to:
Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Neupogen

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Keep the vials in the outer cardboard container to protect from light.
Accidental freezing does not affect the quality of the medicine.
Do not use this medicine after the expiry date stated on the vial and carton
after: Expiry or EXP. The expiry date refers to the last day of the stated month.
Do not use this medicine if you notice discolouration, cloudiness, or particles. The solution should
be clear and colourless.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures will help protect
the environment.

6. Contents of the pack and other information

What Neupogen contains

• The active substance is filgrastim with a strength of 300 micrograms/ml (30 million IU/ml).
• The other ingredients are: glacial acetic acid, sodium hydroxide 1 N, sorbitol (E420), polysorbate 80, water for injections.

What Neupogen looks like and contents of the pack
Neupogen is a clear, colourless solution for injection (injection)/concentrate for solution for infusion (sterile concentrate) contained in a vial.
Neupogen is available in packs containing five vials of 1 ml each.
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
For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Poland
Amgen Biotechnologia Sp. z o.o.
ul. Puławska 145
02-715 Warsaw
Tel.: +48 22 581 3000
[email protected]
This medicinal product is authorised 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.
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 Biocidal Products (www.urpl.gov.pl/).

Information intended exclusively for healthcare professionals:

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 Product Information Leaflet.