What is it and how is it used?
Zarzio contains the active substance filgrastim. It belongs to a group of proteins called cytokines, and is very similar to the granulocyte-colony stimulating factor (G-CSF) produced by the human body. Filgrastim stimulates the bone marrow to produce more white blood cells that help fight infection. If the number of white blood cells is too low (neutropenia), the risk of infection increases.
Anticancer chemotherapy
Zarzio is used to reduce the duration of neutropenia and the occurrence of febrile neutropenia (with fever) which can be caused by the use of cytotoxic anticancer chemotherapy in children and adults. It is not used in patients with chronic myeloid leukaemia (CML) and myelodysplastic syndromes (MDS).
Bone marrow transplantation
Zarzio is used to reduce the duration of neutropenia after high-dose chemotherapy and total body irradiation (radiotherapy) followed by bone marrow transplantation, in children and adults at increased risk of prolonged severe neutropenia.
Peripheral blood stem cell mobilisation
Zarzio is used to stimulate the bone marrow to release (mobilisation) peripheral blood progenitor cells (PBPC, a type of stem cells) into the blood, so that they eventually grow and develop into all types of blood cells: white blood cells, red blood cells and platelets.
If you are a patient with cancer these PBPCs will be removed from your blood and returned after your chemotherapy and/or radiotherapy. As chemotherapy and/or radiotherapy can depress the activity of your bone marrow, this will help to speed up its recovery.
If you donate stem cells for another person, the PBPCs will be removed from your blood and given to the recipient after he/she has received their chemotherapy and/or radiotherapy.
Severe chronic neutropenia
Zarzio is used in children and adults to increase the number of white blood cells and reduce the occurrence and duration of infections related to specific forms of severe chronic neutropenia: congenital (inborn), cyclic (recurring), or idiopathic (without known cause).
HIV infection neutropenia
Zarzio is used to treat persistent neutropenia in patients with advanced HIV infection, in order to reduce the risk of bacterial infections, when other treatments are not appropriate.
What do you have to consider before using it?
Do not use Zarzio
- if you are allergic (hypersensitive) to filgrastim or to any of the other ingredients of Zarzio (listed in section 6. ‘What Zarzio contains’).
Take special care with Zarzio
Please tell your doctor:
- if you have osteoporosis.
- if you have sickle cell anaemia (disorder of the red blood cells leading to a sickle-shaped form of the red blood cells).
- if you have specific blood disorders, such as myelodysplastic syndromes (MDS) or chronic myeloid leukaemia (CML).
- if you act as a donor for another person and are treated with anticoagulants (blood thinning medicines) or you have bleeding problems.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Pregnancy and breast-feeding
It is important to tell your doctor if you are pregnant, think you may be pregnant or plan to get pregnant, as the doctor may decide that you should not use this medicine. Filgrastim could affect your ability to become or stay pregnant.
Your doctor may decide that you should not use filgrastim if you are breast-feeding, as it is not known whether it passes into milk.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Zarzio has no influence on the ability to drive and use machines.
Important information about some of the ingredients of Zarzio
This medicine contains sorbitol (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
How is it used?
The amount of Zarzio you need depends on your bodyweight and the condition you are treated for.
Anticancer chemotherapy
The usual dose is 0.5 million units (MU) per kg bodyweight each day. For example, if you weigh 60 kg, your daily dose will be 30 MU. The first dose should not be administered less than 24 hours following cytotoxic chemotherapy. Your treatment can last up to 14 days. In some disease types, however, longer treatment of up to about 1 month may be required.
Bone marrow transplantation
The usual starting dose is 1 MU per kg bodyweight each day. For example, if you weigh 60 kg, your daily dose will be 60 MU. You will normally receive your first dose at least 24 hours after your chemotherapy, but within 24 hours of receiving your bone marrow transfusion. Your doctor will then test your blood to tell how well your treatment is working and how long it should last.
Peripheral blood stem cell mobilisation
- If you are donating stem cells for yourself, the usual dose is 1 MU per kg bodyweight each day. Zarzio will be given for 5 - 7 consecutive days. Treatment with Zarzio should be maintained until the last stem cell collection.
- If you are donating stem cells for yourself after chemotherapy, the usual dose is 0.5 MU per kg bodyweight each day. Zarzio will be given until the expected lowest level of white blood cells is passed and has recovered to the normal range.
- If you are acting as a stem cell donor for another person, the usual dose is 1 MU per kg bodyweight each day. Zarzio treatment will last for 4 - 5 consecutive days.
Your doctor will perform regular blood tests to determine the best time to collect the stem cells.
Severe chronic neutropenia
The usual starting dose is between 0.5 and 1.2 MU per kg bodyweight each day in a single or divided dose. Your doctor will then test your blood to see how well your treatment is working and to find the dose that is best for you. Long-term treatment with Zarzio is required for neutropenia.
HIV infection neutropenia
The usual starting dose is between 0.1 and 0.4 MU per kg bodyweight each day. Your doctor will test your blood at regular intervals to see how well the treatment is working. Once the number of white cells in your blood have returned to normal it may be possible to reduce the dose frequency to less than once per day. Your doctor will continue to test your blood regularly and will recommend the best dose for you. Long-term treatment with Zarzio may be required to maintain a normal number of white cells in your blood.
Children and adolescents
The dose recommendations are the same as those for adults receiving chemotherapy.
How Zarzio is used
Always use Zarzio exactly as your doctor has told you. You should check with your doctor, nurse or pharmacist if you are not sure. This medicine is given by injection into the tissue just under the skin (subcutaneous injection), or through an intravenous infusion (“a drip”).
Your doctor may decide that it would be more convenient for you to inject Zarzio yourself. Your doctor or nurse will show you how to inject yourself. Do not try to inject yourself if you have not been trained.
Instructions on how to inject yourself with Zarzio can be found at the end of this leaflet.
If you use more Zarzio than you should
If you have used more Zarzio than you should, contact your nurse, doctor or pharmacist immediately.
If you forget to use Zarzio
If you have forgotten a dose of Zarzio, you should contact your doctor to discuss when you should inject the next dose.
If you stop using Zarzio
Your doctor will tell you when you can stop using Zarzio. It is quite normal to have several courses of treatment with Zarzio.
What are possible side effects?
Like all medicines, Zarzio can cause side effects, although not everybody gets them.
Tell your doctor immediately
- if you experience a cough, fever and difficulty breathing since you may develop severe pulmonary side effects like pneumonia and respiratory distress;
- if you get pain in the upper left side of your stomach or pain at the tip of your shoulder since this may relate to a problem with your spleen;
- if you have sudden difficulty breathing or dizziness, swelling of your face or throat, skin weals or rash. As this may be a serious allergic reaction, stop your injection and get medical help immediately.
Side effects may occur with certain frequencies, which are defined as follows:
- very common: affects more than 1 user in 10
- common: affects 1 to 10 users in 100
- uncommon: affects 1 to 10 users in 1,000
- rare: affects 1 to 10 users in 10,000
- very rare: affects less than 1 user in 10,000
- not known: frequency cannot be estimated from the available data.
Very common side effects
- bone, joint and muscle pain
- elevations in blood levels of uric acid and certain enzymes
- decreases in blood glucose
- leukocytosis (an abnormally high number of white blood cells in the blood)
- low level of blood platelets (which increases risk of bleeding or bruising)
- low level of red blood cells (which can make the skin pale and cause weakness and breathlessness)
- headache
- nose bleed
- enlarged spleen
Common side effects
- diarrhoea
- injection site pain
- hair loss
- rash
- enlarged liver
- inflammation of blood vessels of the skin
- loss of calcium from the bones (osteoporosis)
- spleen disorder
Uncommon side effects
- decrease in blood pressure
- allergic-type reactions, including anaphylaxis (dizziness, severe drop in blood pressure, difficulty in breathing), angioedema (painful swelling of the face or throat), difficulty in breathing, low
blood pressure, skin rash, nettle rash; these reactions can occur at the start of the treatment or throughout the treatment
- worsening of rheumatoid arthritis or arthritic symptoms
- blood or protein in the urine
Rare side effects
- vascular disorders, including venoocclusive disease (a disease which affects the liver) and water retention, which can cause swelling in the limbs
Very rare side effects
- difficulties in passing urine
- Sweet's syndrome (plum-coloured, raised, painful lesions on the limbs, sometimes the face and neck, with fever)
- water retention in the lungs, bleeding in the lungs, coughing up of blood, lack of oxygen, inflammation of the lungs (which can cause breathlessness, cough, raised temperature); in some cases, this could lead to respiratory failure or adult respiratory distress syndrome (ARDS, a condition causing increased shortness of breath, in very ill patients), which may be fatal
- sickle cell crises (acute collapse of red blood cells) in patients with sickle cell disease
- rupture of the spleen
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
How should it be stored?
Keep out of the reach and sight of children.
Do not use Zarzio after the expiry date which is stated on the carton and on the syringe label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
The syringe can be removed from the refrigerator and left at room temperature for a single period of maximum 72 hours (but not above 25°C). At the end of this period, the product should not be put back in the refrigerator and should be disposed of.
Keep the pre-filled syringe in the outer carton in order to protect from light.
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 to protect the environment.
What is it?
Zarzio is a solution for injection or infusion (drip into a vein) in a pre-filled syringe. It contains the active substance filgrastim (30 or 48 million units).
Zarzio is a ‘biosimilar’ medicine. This means that Zarzio is similar to a biological medicine that is already authorised in the European Union (EU) and contains the same active substance (also known as the ‘reference medicine’). The reference medicine for Zarzio is Neupogen. For more information on biosimilar medicines, see the question-and-answer document here.
What is it used for?
Zarzio is used to stimulate the production of white blood cells in the following situations: - to reduce the duration of neutropenia (low levels of neutrophils, a type of white blood cell) and the occurrence of febrile neutropenia (neutropenia with fever) in patients receiving chemotherapy (cancer treatment) that is cytotoxic (cell-killing);
- to reduce the duration of neutropenia in patients undergoing treatment to destroy the bone marrow cells before a bone marrow transplant (such as in some patients with leukaemia) if they are at a risk of long-term, severe neutropenia;
- to increase levels of neutrophils and reduce the risk of infections in patients with neutropenia who have a history of severe, repeated infections;
- to treat persistent neutropenia in patients with advanced human immunodeficiency virus (HIV) infection, to reduce the risk of bacterial infections when other treatments are not appropriate. Zarzio can also be used in people who are about to donate blood stem cells for transplant, to help release these cells from the bone marrow.
The medicine can only be obtained with a prescription.
How is it used?
Zarzio is given by injection under the skin or infusion into a vein. How it is given, the dose and the duration of treatment depend on why it is being used, the patient’s body weight and the response to treatment. Zarzio is usually given in a specialised treatment centre, although patients who receive it by injection under the skin may inject themselves once they have been trained appropriately. For more information, see the Package Leaflet.
How does it work?
The active substance in Zarzio, filgrastim, is very similar to a human protein called granulocyte colony stimulating factor (G-CSF). Filgrastim is produced by a method known as ‘recombinant DNA technology’: it is made by a bacterium that has received a gene (DNA), which makes it able to produce filgrastim. The replacement acts in the same way as naturally produced G-CSF by encouraging the bone marrow to produce more white blood cells.
How has it been studied?
Zarzio was studied to show that it is comparable to the reference medicine, Neupogen. Four studies looked at the levels of neutrophils in the blood in a total of 146 healthy volunteers who received Zarzio or Neupogen. The studies looked at the effects of single and repeated administration of various doses of the medicines, either injected under the skin or infused into a vein. The main measure in these studies was the neutrophil count over the first 10 days of treatment.
What benefits has it shown during the studies?
Zarzio and Neupogen brought about similar increases in blood neutrophil counts in healthy volunteers over the course of the studies. This was considered sufficient to demonstrate that the benefits of Zarzio are comparable to those of the reference medicine.
What is the risk associated?
The most common side effect with Zarzio (seen in more than 1 patient in 10) is musculoskeletal pain (pain in the muscles and bones). Other side effects may be seen in more than 1 patient in 10, depending on the condition that Zarzio is being used for. For the full list of all side effects reported with Zarzio, see the Package Leaflet.
Zarzio should not be used in people who may be hypersensitive (allergic) to filgrastim or any of the other ingredients.
Why has it been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that, in accordance with EU requirements, Zarzio has been shown to have a comparable quality, safety and efficacy profile to Neupogen. Therefore, the CHMP’s view was that, as for Neupogen, the benefit outweighs the identified risk. The Committee recommended that Zarzio be given marketing authorisation.
Further information
The European Commission granted a marketing authorisation valid throughout the EU for Zarzio to Sandoz GmbH on 06 February 2009.
Name
Zarzio 48 MU/0.5 ml solution for injection or infusion in
pre-filled syringe
Composition
Each ml of solution contains 96 million units (MU) [equivalent to 960 micrograms (μg)] filgrastim*. Each pre-filled syringe contains 48 MU (equivalent to 480 μg) filgrastim in 0.5 ml.
* recombinant methionylated human granulocyte-colony stimulating factor (G-CSF) produced in E. coli by recombinant DNA technology.
Excipient: Each ml of solution contains 50 mg sorbitol (E420).
For a full list of excipients, see section 6.1.
Pharmaceutical Form
Solution for injection or infusion in pre-filled syringe
Clear, colourless to slightly yellowish solution.
