Prospect: information for the user

Zarzio30MU/0.5ml injectable solution or for infusion in pre-filled syringe
Zarzio48MU/0.5ml injectable solution or for infusion in pre-filled syringe

filgrastim

Read this prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospect. See section 4.

1.What is Zarzio and how is it used

2.What you need to know before starting to use Zarzio

3.How to use Zarzio

4.Possible adverse effects

5.Storage of Zarzio

6.Contents of the package and additional information

Zarzio is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medications called cytokines. Growth factors are proteins that are produced naturally in the body but can also be manufactured through biotechnology for use as medications. Zarzio works by stimulating the bone marrow to produce more white blood cells.

A reduction in the number of white blood cells (neutropenia) can occur for various reasons and makes your body less able to fight off infections. Zarzio stimulates the bone marrow to rapidly produce new white blood cells.

Zarzio can be used:

• to increase the number of white blood cells after chemotherapy treatment to help prevent infections;
• to increase the number of white blood cells after a bone marrow transplant to help prevent infections;
• before undergoing high-dose chemotherapy so that the bone marrow can produce more stem cells that can be collected and returned to the body after treatment. These can be collected from yourself or a donor. The stem cells will return to the bone marrow and produce blood cells;
• to increase the number of white blood cells if you have severe chronic neutropenia to help prevent infections;
• in patients with advanced HIV infection to help reduce the risk of infections.

No use Zarzio

• if you are allergic to filgrastim or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Zarzio.

Inform your doctor before starting treatmentif you have:

• osteoporosis (bone disease);
• anemia of sickle cell disease, as Zarzio may cause sickle cell crises.

Inform your doctor immediately during treatment with Zarzio, if:

• you feel pain in the upper left side of the abdomen, pain in the left lower part of the chest, or pain in the left shoulder tip [these may be symptoms of spleen enlargement (splenomegaly) or possible rupture].
• you have unusual bleeding or bruising (ecchymoses) [these may be symptoms of decreased platelet count (thrombocytopenia), resulting in reduced blood clotting ability].
• you present sudden signs of allergy, such as rash, itching, or urticarial hives on the skin, swelling of the face, lips, tongue, or other parts of the body, difficult breathing, or a hissing sound when breathing (stridor), as they may be signs of severe allergic reaction (hypersensitivity).
• you present swelling in the face or ankles, blood in the urine, or if your urine is brown or if you notice that you urinate less than usual (glomerulonephritis).
• you present symptoms of aortic inflammation (the large blood vessel that carries blood from the heart to the rest of the body); this has been reported in rare cases in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general discomfort, back pain, and increased inflammatory markers. Inform your doctor if you present these symptoms.

Loss of response to filgrastim

If you experience loss of response to filgrastim treatment or if it does not persist, your doctor will investigate the reasons, for example, if you have produced antibodies that neutralize the activity of filgrastim.

Your doctor may wish to monitor you closely; see section4of the leaflet.

If you are a patient with chronic severe neutropenia, you may be at risk of developing blood cancer (leukemia, myelodysplastic syndrome [MDS]). You should consult with 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, do not use Zarzio unless your doctor tells you to.

If you are a stem cell donor, you must be between16and60years old.

Be especially careful with other products that stimulate white blood cells.

Zarzio belongs to a group of medications that stimulate the production of white blood cells. The healthcare professional attending to you must always record the exact product you are using in your medical history.

Other medications and Zarzio

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Pregnancy, breastfeeding, and fertility

Zarzio has not been tested in pregnant women or breastfeeding women.

Zarzio is not recommended for use during pregnancy.

It is essential that you inform your doctor if:

• you are pregnant or breastfeeding,
• you think you may be pregnant, or
• you plan to become pregnant.

If you become pregnant during treatment with Zarzio, inform your doctor.

Unless your doctor tells you otherwise, you should stop breastfeeding if you use Zarzio.

Driving and operating machinery

The influence of Zarzio on your ability to drive and use machines is small. This medication may cause dizziness. It is advisable to wait and see how you feel after using Zarzio and before driving or operating machinery.

Zarzio contains sorbitol and sodium

Zarzio contains sorbitol (E420).

Sorbitol is a source of fructose. If you (or your child) suffer from hereditary fructose intolerance (HFI), a rare genetic disorder, you should not receive this medication. Patients with HFI cannot break down fructose, which may cause severe adverse effects.

Consult your doctor before receiving this medication if you (or your child) suffer from HFI or cannot take sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhea.

This medication contains less than 1mmol of sodium (23mg) per dose volume; this is, essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor, nurse, or pharmacist again.

How is Zarzio administered and what dose should I use?

Zarzio is usually administered as a daily subcutaneous injection into the tissue located just below the skin. It can also be administered as a slow daily intravenous infusion. The usual dose varies depending on your condition and weight. Your doctor will indicate the amount of Zarzio you should use.

Patients undergoing a bone marrow transplant after chemotherapy:

You will usually receive the first dose of Zarzio at least 24 hours after chemotherapy and at least 24 hours after the bone marrow transplant.

You, or the people who care for you, may receive training on how to administer subcutaneous injections so that you can continue treatment at home. However, do not attempt it until a healthcare professional has taught you correctly how to do it.

For how long should I use Zarzio?

You should use Zarzio until your white blood cell count is normal. You will have periodic blood tests to monitor the number of white blood cells in your body. Your doctor will indicate for how long you will need to use Zarzio.

Use in children

Zarzio is used to treat children who receive chemotherapy or have a very low white blood cell count (neutropenia). The dose for children receiving chemotherapy is the same as for adults.

If you use more Zarzio than you should

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

If you forgot to use Zarzio

If you forgot a dose, or the dose injected is too small, contact your doctor as soon as possible. Do not use a double dose to compensate for missed doses.

If you have any other questions about using this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor immediatelyduring treatment:

• if you have an allergic reaction that includes weakness, decreased blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, tongue, or throat (angioedema), and difficulty breathing (dyspnea).
• if you have cough, fever, and difficulty breathing (dyspnea), as they may be signs of acute respiratory distress syndrome (ARDS).
• if you have upper left abdominal pain, lower left chest pain, or shoulder tip pain, as it may be a problem with the spleen (splenomegaly) or spleen rupture.
• if you are being treated for chronic severe neutropenia and have blood in your urine (hematuria). Your doctor may perform regular urine tests if you experience this side effect or have protein in your urine (proteinuria).
• if you experience any or a combination of the following side effects:

• inflammation or swelling, which may be associated with urinating less frequently, difficulty breathing, swelling, and a feeling of fullness in the abdomen, and a general feeling of fatigue. These symptoms usually develop very quickly.

These may be symptoms of a condition called "capillary leak syndrome" that can cause blood to escape from small blood vessels into other parts of your body and requires urgent medical attention.

• if you experience a combination of any of the following symptoms:

• fever, chills, or feeling very cold, rapid heart rate, confusion or disorientation, difficulty breathing, severe pain or discomfort, and sweaty or moist skin.

These may be symptoms of a condition called "sepsis" (or "septicemia"), a severe infection that causes a systemic inflammatory response that can be life-threatening and requires urgent medical attention.

• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients treated with filgrastim. Call your doctor immediately if you experience swelling in your face or ankles, blood in your urine, or if your urine is dark or if you notice that you urinate less than usual.

A common side effect of filgrastim is muscle or bone pain (musculoskeletal pain), which can be relieved by taking common pain relievers. Patients undergoing a stem cell or bone marrow transplant may experience graft-versus-host disease (GVHD). This is a reaction of the donor cells against the recipient, whose signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and lesions in the mouth, intestine, liver, skin, or eyes, lungs, vagina, and joints. In healthy stem cell donors, a very common observation is an increase in white blood cells (leukocytosis) and a decrease in platelets, reducing blood clotting ability (thrombocytopenia), both of which will be monitored by your doctor.

Very common side effects(may affect more than1in 10people)

• low platelet count, reducing blood clotting ability (thrombocytopenia)
• low red blood cell count (anemia)
• headache
• diarrhea
• vomiting
• nausea
• unusual hair loss (alopecia)
• fatigue (fatigue)
• irritation and swelling of the digestive tract mucosa from mouth to anus (mucosal inflammation)
• fever (pyrexia)

Common side effects(may affect up to1in 10people)

• inflammation of the lungs (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• loss of appetite
• sleep problems (insomnia)
• dizziness
• numbness or tingling in the hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• mouth and throat pain (orofacial pain)
• nasal bleeding (epistaxis)
• constipation
• mouth pain
• enlarged liver (hepatomegaly)
• rash
• skin redness (erythema)
• muscle spasms
• painful urination (dysuria)
• chest pain
• pain
• generalized weakness (asthenia)
• general feeling of illness
• swelling of the hands and feet (peripheral edema)
• increase in some blood enzymes
• changes in blood biochemistry parameters
• transfusion reaction

Rare side effects(may affect up to1in 1,000people):

• intense bone, chest, intestine, or joint pain (sickle cell anemia crisis)
• potentially life-threatening allergic reaction (anaphylactic reaction)
• joint pain and swelling similar to gout (pseudogout)
• change in the way the body regulates fluid volume that can cause swelling (fluid volume alterations)
• inflammation of the skin blood vessels (cutaneous vasculitis)
• painful, dark red ulcers with inflammatory halo on extremities and sometimes face and neck, accompanied by fever (Sweet syndrome)
• worsening of rheumatoid arthritis
• abnormal urine test results
• bone density reduction
• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see section 2
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis)

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the syringe label after CAD and EXP, respectively. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C).

Store the preloaded syringe in the outer packaging to protect it from light.

Accidental freezing will not cause damage to Zarzio.

The syringe may be removed from the refrigerator and left at room temperature for a single period of up to 8 days (but at a temperature not exceeding 25 °C). After this period, the product should not be re-refrigerated and should be discarded.

Do not use this medication if you observe discoloration, turbidity, or particles; it should be a transparent liquid, between colorless and slightly yellowish.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Zarzio

• The active ingredient is filgrastim.

Zarzio30MIU/0.5ml injectable solution or for infusion in pre-filled syringe:each pre-filled syringe contains30MIU of filgrastim in0.5ml, whichcorresponds to60MIU/ml.

Zarzio48MIU/0.5ml injectable solution or for infusion in pre-filled syringe:each pre-filled syringe contains48MIU of filgrastim in0.5ml, whichcorresponds to96MIU/ml.

• The other components are glutamic acid, sorbitol(E 420), polisorbate80, sodium hydroxide and water for injection preparations.See section2 “Zarzio contains sorbitol and sodium”.

Aspect of the product and content of the package

Zarzio is a transparent and colorless to slightly yellowish injectable solution or for infusion in pre-filled syringe.

Zarzio is available in packages of1,3,5or10pre-filled syringes with injection needle and safety needle protector.

Only some package sizes may be marketed.

Marketing Authorization Holder

SandozGmbH

Biochemiestr.10

6250Kundl

Austria

Responsible for manufacturing

SandozGmbH

Biochemiestr.10

6336Langkampfen

Austria

Novartis Pharmaceutical Manufacturing GmbH

Biochemiestrasse 10

6336 Langkampfen

Austria

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet: {MM/YYYY}

For detailed information about this medicinal product, please visit the website of theEuropean Medicines Agency:http://www.ema.europa.eu/.

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Self-injection instructions

This section contains information on how to administer a Zarzio injection yourself.It is essential that you do not attempt to administer the injection without first having been instructed by your doctor or nurse.Zarzio is supplied with a safety needle protector, which your doctor or nurse will teach you how to use. If you are unsure about administering the injection yourself or have any questions, consult your doctor or nurse.

Warning: Do not use if the syringe has fallen onto a hard surface or has fallen after removing the needle cap.

1. Wash your hands.
2. Remove a syringe from the package and remove the needle cap for injection. Syringes have graduation rings to allow partial use if necessary. Each graduation ring corresponds to a volume of0.1ml. If partial use of a syringe is necessary, remove the unwanted solution before injection.
3. Clean the skin at the injection site with an alcohol swab.
4. Form a fold in the skin by pinching it between your thumb and index finger-

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This information is intended for healthcare professionals:

The solution should be visually inspected before use. Only solutions that are transparent and particle-free should be used. Accidental exposure to freezing temperatures does not adversely affect the stability of Zarzio.

Zarzio does not contain preservatives: due to the potential risk of microbiological contamination, Zarzio syringes are for single use only.

Pre-dilution before administration (optional)

Zarzio can be diluted, if necessary, in a glucose solution of50mg/ml(at5%). Zarzio should not be diluted with sodium chloride solutions.

It is not recommended to dilute to final concentrations <0.2MIU/ml(2micrograms/ml).

In patients treated with filgrastim diluted to concentrations <1.5MIU/ml(15micrograms/ml), human serum albumin (HSA) should be added to a final concentration of2mg/ml.

Example: if the final injection volume is20ml and the total dose of filgrastim is less than30MIU(300micrograms), 0.2ml of a solution of human serum albuminof200mg/ml(at20%) Ph.Eur.

Diluted in a glucose solutionof50mg/ml(at5%), filgrastim is compatible with glass and various plastics, including polyvinyl chloride, polyolefin (a copolymer of polypropylene and polyethylene), and polypropylene.

After dilution: it has been demonstrated that, during use, the diluted solution for infusion remains physico-chemically stable for24hours at2–8 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times during use and the conditions prior to it are the responsibility of the user and normally should not exceed24hours at2–8 °C, unless the dilution was performed in validated and controlled aseptic conditions.

Use of the pre-filled syringe with safety needle protector

The safety needle protector covers the needle after the injection has been made to prevent accidental needle sticks. This does not affect the way the syringe is used. Slowly and uniformly push the plunger until the entire dose has been administered and the plunger cannot move any further. Remove the syringe while maintaining the pressure on the plunger. The safety needle protector will cover the needle once the plunger is released.

Disposal

The disposal of unused medicinal product or waste material should be in accordance with local requirements.