30 ME/0.5 ml and 48 ME/0.5 ml injection or infusion solution, solution, in a pre-filled syringe
Filgrastim
What Zarzio is and what it is used for
Zarzio is a growth factor for white blood cells (granulocyte colony-stimulating factor) and belongs to a group of proteins called cytokines. Growth factors are proteins that are produced naturally in the body, but they can also be manufactured with biotechnology to be used in medicines. Marzio works by stimulating the bone marrow so that it forms more white blood cells.
A decrease in the number of white blood cells ( neutropenia ) can occur for various reasons and weakens the body’s ability to fight infection. Marzio stimulates the bone marrow to rapidly produce new white blood cells.
Marzio can be used:
- to increase the number of white blood cells after treatment with chemotherapy to prevent infection,
- to increase the number of white blood cells after a bone marrow transplant to prevent infection,
- before high-dose chemotherapy to make the bone marrow produce more stem cells that can be collected and returned to you after treatment. These can be taken from you or a donor. The stem cells then go back to the bone marrow and produce blood cells,
- to increase the number of white blood cells if you have severe chronic neutropenia to prevent infection,
- in patients with advanced HIV infection to reduce the risk of infection.
What you need to know before you use Zarzio
Do not use Zarzio
- if you are allergic to filgrastim or any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Zarzio.
Inform your doctor before starting treatment if you have :
- osteoporosis _
- sickle cell anemia because Zarzio can cause sickle cell crisis.
During treatment with Zarzio, inform your doctor immediately if you:
- have pain in the upper left part of the abdomen (abdominal pain), pain under the left rib cage or in the tip of the left shoulder blade [these may be symptoms of an enlarged spleen ( splenomegaly ) or possibly a ruptured spleen ]
- notice abnormal bleeding or bruising [these may be symptoms of low platelet count ( thrombocytopenia ), which impairs the blood’s ability to clot]
- get 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, wheezing, or difficulty breathing, as these may be signs of a severe allergic reaction (hypersensitivity).
- get swelling of the face or ankles, blood in the urine, or brown-colored urine, or if you notice that you urinate less than usual ( glomerulonephritis ).
Inflammation of the aorta (the large blood vessel that carries blood from the heart to the body) has been reported at a frequency of “rare” in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Tell your doctor if you experience these symptoms.
Decreased response to filgrastim
If you feel that you no longer respond to the filgrastim treatment or your response to treatment decreases, the doctor will investigate the reasons for this, i.a. whether you have developed antibodies that neutralize the effects of filgrastim.
The doctor may want 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 [MSD]). You should talk to the doctor about your risk of developing blood cancer and what tests should be done. If you develop or are at risk of developing blood cancer, you should not use Zarzio unless your doctor tells you to.
If you are a stem cell donor, you must be between 16 and 60 years old.
Be especially careful with other products that stimulate white blood cells
Marzio belongs to a group of drugs that stimulate the production of white blood cells. Healthcare professionals should always record exactly which product they use.
Other medicines and Zarzio
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Zarzio has not been tested on pregnant or lactating women.
Zarzio is not recommended during pregnancy.
You must tell your doctor if you:
- are pregnant or breastfeeding
- think you might be pregnant
- planning to have children.
Inform the doctor if you become pregnant during treatment with Zarzio.
Unless your doctor tells you otherwise, you must stop breastfeeding if you are using Zarzio.
Driving ability and use of machinery
Marzio may have a minor influence on the ability to drive and use machines. This medicine may cause dizziness. It is wise to wait and see how you feel after taking Zarzio and before driving or using machines.
Zarzio contains sorbitol
Zarzio contains sorbitol (E420).
Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance, a rare, hereditary disease, you (or your child) should not use this medicine. Patients with hereditary fructose intolerance cannot break down fructose, which can cause serious side effects.
Consult a doctor before using this medicine if you (or your child) have hereditary fructose intolerance, or if your child can no longer eat sweet foods or drinks without feeling sick, vomiting, or experiencing discomforts such as bloating, stomach cramps, or diarrhea.
How to use Zarzio
Always use this medicine as directed by your doctor. Ask your doctor or pharmacist if you are unsure.
How is Zarzio given and how much should I take?
Zarzio is usually given as a daily injection into a tissue just under the skin (so-called subcutaneous injection ). It can also be given as a slow injection into the vein (so-called intravenous infusion ). The usual dose varies depending on your illness and weight. The doctor will tell you how much Zarzio you should take.
Patients undergoing bone marrow transplantation after chemotherapy:
You will normally receive your first dose of Zarzio at least 24 hours after chemotherapy and at least 24 hours after you have had a bone marrow transplant.
You, or the people caring for you, can be trained in how to give a subcutaneous injection so that you can continue your treatment at home. However, you should not attempt to do this unless you have first been properly trained by healthcare professionals.
How long do I need to take Zarzio?
You need to take Zarzio until the white blood cell count is normal. Blood samples will be taken regularly to check the number of white blood cells in the body. The doctor will tell you how long you need to take Zarzio.
Use for children
Zarzio is used to treat children who are receiving chemotherapy or who have very low white blood cell counts ( neutropenia ). The dose for children receiving chemotherapy is the same as for adults.
If you use too much Zarzio
Do not increase the dose your doctor has given you. If you think you have injected more Zarzio than you should, contact your doctor as soon as possible.
If you forget to use Zarzio
If you have missed an injection or injected too little, contact your doctor as soon as possible. Do not take a double dose to make up for a missed dose.
If you have any further questions about this medicine, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately during treatment:
- if you have an allergic reaction with weakness, drop in blood pressure, difficulty breathing, swelling of the face ( anaphylaxis ), skin rash, itchy rash ( urticaria ), swelling of the face, lips, mouth, tongue or throat ( angioedema ) or shortness of breath ( dyspnoea ).
- if you suffer from cough, fever, and difficulty breathing ( dyspnoea ), as these may be signs of acute respiratory distress syndrome (ARDS).
- if you get pain in the upper left part of the abdomen (abdominal pain), pain under the left rib cage or at the tip of the shoulder blade, as this may be due to problems with the spleen [enlargement of the spleen ( splenomegaly ) or ruptured spleen ].
- if you are being treated for severe chronic neutropenia and have blood in the urine ( haematuria ). The doctor may test the urine regularly if you experience this side effect or if the protein is detected in the urine ( proteinuria ).
- if you experience one or more of the following side effects:
- swelling or fluid accumulation, which may be associated with urinating less often than usual, breathing difficulties, swollen abdomen, and feeling of over-satiation, and a general feeling of tiredness. These symptoms often develop quickly.
- These symptoms may be signs of a condition called “capillary leak syndrome” which causes blood to leak from small blood vessels into the body. This condition must be treated immediately.
- if you experience any of the following symptoms:
- fever or chills or feeling very cold, fast heart rate, confusion or disorientation, shortness of breath, extreme pain or discomfort, and clammy or sweaty skin.
- These can 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 must be treated immediately.
- if you get kidney damage ( glomerulonephritis ). Kidney damage has been seen in patients receiving filgrastim. Contact a doctor immediately if you develop swelling of the face or ankles, blood in the urine, or brown-colored urine, or if you notice that you urinate less than usual.
A common side effect when using filgrastim is a pain in the muscles or bones (musculoskeletal pain), which can be relieved with common painkillers ( analgesics ). In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease (GvHD) may occur – this is a reaction of the donor cells against the patient receiving the transplant; signs and symptoms are rashes on the palms of the hands and soles of the feet and ulcers in the mouth, gut, liver, skin or eyes, lungs, vagina, and joints. A side effect that is very common in healthy stem cell donors is an increased number of white blood cells ( leukocytosis ) and a decreased number platelets , which impair the blood’s ability to clot ( thrombocytopenia ), your doctor will check this.
Very common side effects ( seen in more than 1 in 10 people)
- reduced number of platelets, which reduces the blood’s ability to clot ( thrombocytopenia )
- the low number of red blood cells ( anemia )
- headache
- diarrhea
- vomiting
- nausea
- abnormal hair loss or thinning ( alopecia )
- fatigue (exhaustion)
- soreness and swelling of the lining of the digestive tract that runs from the mouth to the anus (mucositis)
- fever ( pyrexia ).
Common side effects ( seen in up to 1 in 10 people)
- inflammation of the lung ( bronchitis )
- upper respiratory tract infection
- urinary tract infection
- decreased appetite
- insomnia _ _
- dizziness
- reduced sensitivity, especially in the skin ( hypesthesia )
- tingling or numbness in the hands or feet ( paresthesia )
- low blood pressure ( hypotension )
- high blood pressure ( hypertension )
- cough
- coughing up blood (hemoptysis)
- pain in the mouth and throat ( oropharyngeal pain)
- nosebleeds ( epistaxis )
- constipation
- pain in the mouth
- enlarged liver ( hepatomegaly )
- rash
- skin redness ( erythema )
- muscle spasm
- pain when urinating ( dysuria )
- chest pain
- pain
- a general feeling of weakness ( asthenia )
- general malaise
- swollen hands and feet (peripheral edema )
- increase of certain enzymes in the blood
- changes in the chemical composition of the blood
- transfusion reaction
Uncommon side effects ( seen in up to 1 in 100 people)
- increased number of white blood cells ( leukocytosis )
- allergic reaction (hypersensitivity)
- rejection of transplanted bone marrow ( graft versus host disease)
- high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased levels of uric acid in the blood)
- liver damage due to blockage of the small veins in the liver (veno-occlusive disease)
- lungs not working properly leading to breathlessness (respiratory failure)
- swelling and/or fluid in the lungs ( pulmonary edema )
- pneumonia (interstitial lung disease)
- abnormalities on chest X-ray (pulmonary infiltration)
- bleeding in the lung (pulmonary hemorrhage)
- reduced oxygen uptake in the lung ( hypoxia )
- patchy skin rash (drug rash)
- a disease that makes the bones less dense, so that they become weaker, more fragile, and break more easily ( osteoporosis )
- injection site reaction
Rare side effects ( seen in up to 1 in 1,000 people):
- severe pain in the bones, chest, intestines, or joints (sickle cell crisis)
- sudden life-threatening allergic reaction ( anaphylactic reaction )
- pain and swelling in the joints similar to gout (pseudogout)
- changes in how the body regulates fluid which can lead to swelling (fluid volume disturbance)
- inflammation of the blood vessels in the skin ( cutaneous vasculitis )
- plum-colored, raised, painful sores on the arms and legs and sometimes on the face and neck with fever (Sweet’s syndrome)
- aggravated rheumatoid arthritis
- unusual changes in the urine
- decreased bone density
- inflammation of the aorta (the large blood vessel that transports blood from the heart to the body), see section 2.
How to store Zarzio
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the carton and the syringe label after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2–8 °C).
Store the pre-filled syringe in the outer carton. Light sensitive.
Accidental freezing does not damage Zarzio.
The syringe can be taken out of the refrigerator and left at room temperature for a single period of a maximum of 8 days (but not above 25 ºC). At the end of this period, the product must not be put back in the refrigerator but must be discarded.
Do not use this medicine if you notice discoloration, cloudiness, or particles, the liquid should be clear and colorless to slightly yellowish.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is filgrastim. Marzio 30 ME/0.5 ml solution for injection or infusion, in the pre-filled syringe: A pre-filled syringe contains 30 ME filgrastim in 0.5 ml corresponding to 60 ME/ml. Marzio 48 ME/0.5 ml solution for injection or infusion, in the pre-filled syringe: A pre-filled syringe contains 48 ME filgrastim in 0.5 ml corresponding to 96 ME/ml.
- Other ingredients are glutamic acid, sorbitol (E420), polysorbate 80, and water for injections.
Appearance and package sizes of the medicine
Zarzio is a clear, colorless slightly yellowish solution for injection or infusion, in a pre-filled syringe.
Zarzio is available in packs containing 1, 3, 5, or 10 pre-filled syringes with an injection needle and with or without a needle guard.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Sandoz GmbH
Biochemistr. 10
6250 Kundl
Austria
Manufacturer
Sandoz GmbH
Biochemistr. 10
6336 Langkampfen
Austria