Ziextenzo 6 mg solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Ziextenzo 6 mg solution for injection in pre-filled syringe

pegfilgrastim

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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it could harm them.
• If you get any side effects, talk to your doctor, pharmacist, or nurse, even if the side effect is not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Ziextenzo is and what it is used for

Ziextenzo contains the active substance pegfilgrastim. Pegfilgrastim is a protein produced by biotechnology in the bacterium E. coli. Pegfilgrastim belongs to a group of proteins called cytokines, and is very similar to a natural protein (granulocyte colony-stimulating factor) produced by our body.

Ziextenzo is used to reduce the duration of neutropenia (low white blood cell count) and the incidence of febrile neutropenia (low white blood cell count and fever) that can occur as a result of cytotoxic chemotherapy (medicines that destroy rapidly dividing cells). White blood cells are important because they help fight infections. These cells are sensitive to the effects of chemotherapy, which can cause their numbers to drop. If the number of white blood cells becomes too low, there may not be enough to fight bacteria, increasing the risk of developing an infection.

Your doctor has prescribed Ziextenzo to stimulate your bone marrow (the part inside the bone where blood cells are produced) to produce more white blood cells to help you fight infections.

2. What you need to know before using Ziextenzo

Do not use Ziextenzo

• if you are allergic to pegfilgrastim, 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 Ziextenzo:

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), redness and flushing, skin rash, or itching in areas of the skin.

• if you experience cough, fever, and difficulty breathing. This may be a sign of acute respiratory distress syndrome (ARDS).

• if you experience any one or a combination of the following adverse effects:

• swelling that may be associated with reduced frequency of urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue.

These may be symptoms of a condition called "Capillary Leak Syndrome," which can cause blood to leak from small blood vessels into other areas of your body. See section 4.

• if you have pain in the upper left side of the abdomen or pain at the tip of the shoulder. This may be a sign of a spleen problem (splenomegaly).
• if you recently had a severe lung infection (pneumonia), fluid in the lungs (pulmonary edema), lung inflammation (pulmonary interstitial disease), or an abnormal chest X-ray result (pulmonary infiltration).
• if you are aware of any blood cell count disorders (e.g., increased white blood cell count or anemia) or a reduced platelet count, which may impair the blood's ability to clot (thrombocytopenia). Your doctor may want to monitor you more closely.
• if you have sickle cell anemia. Your doctor may monitor your condition more closely.
• if you are a patient with breast cancer or lung cancer, combination treatment with Ziextenzo, chemotherapy, and/or radiotherapy may increase the risk of developing a pre-leukemic blood disorder called myelodysplastic syndrome (MDS) or a blood neoplasm called acute myeloid leukemia (AML). Symptoms may include fatigue, fever, easy bruising, or bleeding.
• if you experience sudden signs of allergy such as skin rash, itching, or hives, swelling of the face, lips, tongue, or other body parts, shortness of breath, wheezing, or difficulty breathing, as these may be signs of a severe allergic reaction.
• if you have symptoms of inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), which has rarely been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general malaise, back pain, and elevated inflammatory markers. Inform your doctor if you experience these symptoms.

Your doctor will perform regular blood and urine tests, as pegfilgrastim may damage the small filters in the kidneys (glomerulonephritis).

Severe skin reactions (Stevens-Johnson syndrome) have been reported with the use of Ziextenzo. Stop using Ziextenzo and seek immediate medical attention if you notice any of the symptoms described in section 4.

You should discuss with your doctor the risk of developing blood cancer. If you have or may develop blood cancer, you should not use Ziextenzo unless advised by your doctor.

Loss of response to pegfilgrastim

If you experience a loss of response or are unable to maintain a response to pegfilgrastim treatment, your doctor will investigate possible causes, including whether you have developed antibodies that may neutralize the activity of pegfilgrastim.

Other medicines and Ziextenzo

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine. Pegfilgrastim has not been used in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you think you may be pregnant; or
• you are planning to become pregnant.

If you become pregnant while being treated with Ziextenzo, please inform your doctor.

Unless your doctor advises otherwise, you should stop breastfeeding while using Ziextenzo.

Driving and using machines

The effect of Ziextenzo on the ability to drive and use machines is negligible or none.

Ziextenzo contains sorbitol (E 420) and sodium.

This medicine contains 30 mg of sorbitol in each pre-filled syringe equivalent to 50 mg/ml.

This medicine contains less than 1 mmol of sodium (23 mg) per 6 mg dose; hence, it is essentially "sodium-free."

3. How to use Ziextenzo

Ziextenzo is indicated in patients over 18 years of age.

Follow exactly the administration instructions for Ziextenzo provided by your doctor. If you have any doubts, ask your doctor or pharmacist. The usual dose is one 6 mg subcutaneous injection (under the skin) using a pre-filled syringe, to be administered at the end of each chemotherapy cycle, starting 24 hours after your last dose of chemotherapy.

Self-injection of Ziextenzo

Your doctor may consider it more convenient for you to self-inject Ziextenzo. Your doctor or nurse will teach you how to do this. Do not attempt it if you have not been trained.

For further instructions on how to self-inject Ziextenzo, read the section at the end of this leaflet.

Do not shake Ziextenzo vigorously, as this may affect its activity.

If you use more Ziextenzo than you should

If you use more Ziextenzo than you should, inform your doctor, pharmacist, or nurse.

If you forget to use Ziextenzo

If you are self-injecting and have forgotten to administer your dose of Ziextenzo, contact your doctor to determine when the next dose should be administered.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Contact your doctor immediately if you experience any of the following adverse effects, or a combination of them:

• swelling that may be associated with reduced urination, difficulty breathing, abdominal swelling and bloating, and a general feeling of fatigue. These symptoms usually develop very rapidly.

These may be symptoms of a condition that occurs infrequently (affecting up to 1 in 100 people), called "capillary leak syndrome," which can cause blood to leak from small blood vessels into other parts of the body and requires urgent medical attention.

Very common adverse effects (may affect more than 1 in 10 patients):

• bone pain. Your doctor will advise you on what you can take to relieve the pain.
• nausea and headache.

Common adverse effects (may affect up to 1 in 10 patients):

• pain at the injection site.
• general pain, joint pain, and muscle pain.
• some changes in your blood may occur, which will be detected through periodic blood tests. The number of white blood cells may temporarily increase. The number of platelets may decrease, which could lead to bruising.

Uncommon adverse effects (may affect up to 1 in 100 patients):

• allergic-type reactions, including redness, flushing, skin rash, and inflamed, itchy skin.
• severe allergic reactions, including anaphylaxis (weakness, low blood pressure, difficulty breathing, facial swelling).
• enlargement of the spleen.
• rupture of the spleen. Some cases of spleen rupture have been fatal. It is important that you contact your doctor immediately if you experience pain in the upper left part of the abdomen or left shoulder, as these symptoms could indicate a problem with your spleen.
• respiratory problems. If you develop cough, fever, or difficulty breathing, consult your doctor.
• cases of Sweet's syndrome (painful, inflamed, purplish skin lesions on the limbs, and sometimes on the face and neck, accompanied by fever) have been reported, although other factors may be involved.
• cutaneous vasculitis (inflammation of the blood vessels in the skin).
• damage to the small filters within the kidneys (glomerulonephritis).
• redness at the injection site.
• coughing up blood (haemoptysis).
• haematological disorders (myelodysplastic syndrome [MDS] or acute myeloid leukaemia [AML]).

Rare adverse effects (may affect up to 1 in 1,000 patients):

• inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2.
• bleeding from the lung (pulmonary haemorrhage).
• Stevens-Johnson syndrome, which may appear as red, target-like or circular skin lesions, often with central blisters, typically on the trunk, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes; it may be preceded by fever and flu-like symptoms. Stop using Ziextenzo and contact your doctor or seek immediate medical attention if you develop these symptoms. See section 2.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report adverse effects directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ziextenzo

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

Do not use this medicine after the expiry date which is stated on the carton and on the label of the syringe after EXP. The expiry date refers to the last day of the month indicated.

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

Ziextenzo may be kept outside the refrigerator at room temperature (provided it does not exceed 35 °C) for a maximum of 120 hours. Once a syringe has been removed from the refrigerator and has reached room temperature (not exceeding 35 °C), it must be used within 120 hours or discarded.

Do not freeze. Ziextenzo may be used if accidental freezing occurs, for a period of less than 24 hours.

Keep the container in the outer packaging to protect it from light.

Do not use this medicine if you notice that the solution is not completely clear or contains particles.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Ziextenzo

• The active substance is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 ml of solution.
• The other components are glacial acetic acid, sorbitol (E 420), polysorbate 20, sodium hydroxide and water for injections. See section 2 “Ziextenzo contains sorbitol (E 420) and sodium”.

Appearance of the product and contents of the pack

Ziextenzo is a clear, colourless to slightly yellowish injectable solution (injection) in a pre-filled syringe (6 mg/0.6 ml).

Each pack contains 1 glass pre-filled syringe with a rubber plunger stopper (bromobutyl rubber, latex-free), a plunger rod, a 29-gauge stainless steel needle, and a needle cap (thermoplastic elastomer, latex-free). The syringes are supplied with an automatic needle safety guard.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Manufacturer

Sandoz GmbH

Biochemiestr. 10

6336 Langkampfen

Austria

Novartis Pharmaceutical Manufacturing GmbH

Biochemiestrasse 10

6336 Langkampfen

Austria

Further information about this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: .

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

This leaflet is available on the European Medicines Agency's website in all languages of the European Union/European Economic Area.

Instructions for using the Ziextenzo pre-filled syringe with needle shield

To help prevent possible infections and to ensure you use the medicine correctly, it is important that you follow these instructions.

Read ALL instructions before injecting yourself. It is important that you do not attempt to self-inject until a doctor, nurse, or pharmacist has shown you how to do so. The pack contains the pre-filled syringe sealed individually in a plastic blister.

After injecting the medicine, the needle shield is activated to cover the needle. The purpose of the needle shield is to prevent accidental needlestick injuries to healthcare professionals, caregivers, and patients after the injection.

Important safety information

Caution: Keep the pre-filled syringe out of sight and reach of children.

1. Do not open the carton until you are ready to use the pre-filled syringe.

2. Do not use the pre-filled syringe if the blister seal is broken, as it may not be safe to use.

3. Do not use the pre-filled syringe if there is liquid in the blister. Do not use the pre-filled syringe if the needle cap is missing or not properly in place. In such cases, return the entire product package to the pharmacy.

4. Never leave the pre-filled syringe unattended where others could handle it.

5. Do not shake the pre-filled syringe.

6. Avoid touching the wings of the needle shield before use. If touched, the needle shield may activate prematurely.

7. Do not remove the needle cap until immediately before administering the injection.

8. The pre-filled syringe is not reusable. Immediately dispose of the used syringe in a sharps container after use.

9. Do not use if the syringe has been dropped onto a hard surface or dropped after removing the needle cap.

Storage of the Ziextenzo pre-filled syringe

1. Store the pre-filled syringe in its blister packaging inside the carton to protect it from light.

2. Store in the refrigerator at 2 °C to 8 °C. Do not freeze.

3. Before use, remove the pre-filled syringe from the refrigerator and allow Ziextenzo to reach room temperature (up to a maximum of 35 °C) for approximately 15–30 minutes.

4. Do not use the pre-filled syringe after the expiry date stated on the carton or syringe label. If expired, return the complete package to the pharmacy.

Injection site

Preparing the ready-to-use Ziextenzo pre-filled syringe

1. Remove the carton containing the pre-filled syringe in its blister packaging from the refrigerator and leave it unopened for approximately 15–30 minutes to allow it to reach room temperature.

2. When ready to use the pre-filled syringe, open the blister pack and wash your hands thoroughly with soap and water.

3. Clean the injection site with an alcohol swab.

4. Remove the pre-filled syringe from the blister pack by holding it in the middle section, as shown below. Do not touch the plunger. Do not touch the needle cap.

1. Check that the transparent plastic needle shield is properly positioned over the glass syringe barrel. If the transparent needle shield covers the needle cap (as illustrated below), the syringe shield has been activated and this syringe must not be used; instead, use a new syringe. The figure below shows a syringe ready for use.

1. Examine the pre-filled syringe. The liquid should be clear, ranging in color from colorless to slightly yellowish. A small air bubble in the liquid may be visible, which is normal. Do not use the pre-filled syringe if other particles or discoloration are observed.
2. Do not use the syringe if it is broken or has been activated. Return the Ziextenzo pre-filled syringe and its packaging to the pharmacy.

How to use the Ziextenzo pre-filled syringe

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