Ziextenzo

Package leaflet: Information for the user

Ziextenzo 6 mg solution for injection in pre-filled syringe

pegfilgrastim
Please 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 yours, because it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. 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 using biotechnology in a bacterial cell called Escherichia coli. It belongs to a group of proteins known as 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 number of white blood cells) and the occurrence of febrile neutropenia (low number of white blood cells with fever) that may be caused by cytotoxic chemotherapy (medicines that destroy rapidly growing cells). White blood cells are important because they help the body fight infections. These cells are highly sensitive to the effects of chemotherapy; this can cause a reduction in the number of these cells in the body. If the number of white blood cells drops to a low level, there may not be enough left to fight bacteria, and you may be at increased risk of developing an infection.
Your doctor has prescribed Ziextenzo to stimulate the bone marrow (the part of the bones that produces blood cells) to produce more white blood cells, helping your body to 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 have an allergic reaction including weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), flushing and redness, rash, or itchy skin areas.
• if you have cough, fever, and difficulty breathing. This may be a sign of Acute Respiratory Distress Syndrome (ARDS).
• if you experience one or more of the following side effects:
  • swelling or bloating, which may be associated with reduced fluid passage, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These could be symptoms of a condition called "Capillary Leak Syndrome" that causes leakage of blood from small vessels in the body. See section 4.
• if you have pain in the upper left side of the abdomen or shoulder tip pain. These could be signs of a spleen problem (splenomegaly).
• if you have recently had a serious lung infection (pneumonia), fluid in the lungs (pulmonary edema), lung inflammation (pulmonary interstitial disease), or an abnormal finding on X-ray (pulmonary infiltration).
• if you know you have abnormal blood cell counts (e.g. elevated white blood cells or anemia) or decreased platelet levels, which reduces the blood's ability to clot (thrombocytopenia). Your doctor may wish to monitor you closely.
• if you have sickle cell anaemia. Your doctor may wish to monitor you closely.
• if you have breast or lung cancer, Ziextenzo in combination with chemotherapy and/or radiotherapy may increase the risk of a pre-cancerous blood condition called myelodysplastic syndrome (MDS) or a blood cancer called acute myeloid leukaemia (AML). Symptoms may include fatigue, fever, and easy bruising or bleeding.
• if you suddenly develop signs of allergy such as rash, hives, or skin itching, swelling of the face, lips, tongue, or other body parts, shortness of breath, wheezing, or difficulty breathing—these could be signs of a serious allergic reaction.
• if you have symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, malaise, back pain, and elevated markers of inflammation. Inform your doctor if you experience any of these symptoms.

Your doctor will regularly check your blood and urine, as pegfilgrastim may damage the tiny filters in your kidneys (glomerulonephritis).
Severe skin reactions (Stevens-Johnson syndrome) have been observed with the use of Ziextenzo. If you notice any of the symptoms described in section 4, stop using Ziextenzo and seek immediate medical help.
Discuss with your doctor the risks of developing blood cancer. If you have or are likely to develop blood cancer, you should not use Ziextenzo unless otherwise instructed by your doctor.
Loss of response to pegfilgrastim
If you experience a reduced response or failure to maintain response to pegfilgrastim treatment, your doctor will investigate possible causes, including the possibility that you have developed antibodies that neutralize the activity of pegfilgrastim.
Other medicines and Ziextenzo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine. Pegfilgrastim has not been studied in pregnant women. It is important that you inform your doctor if:

• you are pregnant;
• you suspect you may be pregnant; or
• you are planning a pregnancy.

If you become pregnant during treatment with Ziextenzo, inform your doctor.
Unless otherwise advised by your doctor, you must stop breastfeeding while using Ziextenzo.
Driving and using machines
Ziextenzo does not affect or has a negligible effect on the ability to drive or operate machinery.
Ziextenzo contains sorbitol (E420) and sodium
This medicine contains 30 mg of sorbitol per pre-filled syringe, equivalent to 50 mg/mL.
This medicine contains less than 1 mmol (23 mg) of sodium per 6 mg dose, i.e. essentially 'sodium-free'.

3. How to use Ziextenzo

Ziextenzo is intended for adults aged 18 years and older.
Use Ziextenzo exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The usual dose is one subcutaneous injection (an injection under the skin) of 6 mg, to be administered using a pre-filled syringe at least 24 hours after the last dose of chemotherapy, at the end of each chemotherapy cycle.

How to self-administer the Ziextenzo injection
Your doctor may decide that it is better for you to self-inject Ziextenzo. Your doctor or nurse will show you how to administer the injection. Do not attempt to self-inject unless you have been properly instructed.
Refer to the section at the end of this leaflet for further instructions on how to self-administer the Ziextenzo injection.
Do not shake Ziextenzo vigorously, as this may impair its activity.

If you use more Ziextenzo than you should
If you use more Ziextenzo than prescribed, contact your doctor, pharmacist, or nurse immediately.

If you forget to inject Ziextenzo
If you are self-injecting and have missed your dose of Ziextenzo, contact your doctor to determine when to administer the next injection.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Inform your doctor immediately if you experience any one or a combination of the following side effects:

• swelling or puffiness, which may be associated with less frequent urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly.

These could be symptoms of an uncommon condition (may affect up to 1 in 100 people) called "Capillary Leak Syndrome", which causes blood to leak from small blood vessels into the body and requires urgent medical treatment.

Very common side effects (may affect more than 1 in 10 people):

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

Common side effects (may affect up to 1 in 10 people):

• pain at the injection site.
• general discomfort and joint and muscle pain.
• some blood changes may occur, but these will be detected during routine blood tests. White blood cell levels may rise temporarily. Platelet levels may decrease, leading to bruising.

Uncommon side effects (may affect up to 1 in 100 people):

• allergic-type reactions, including flushing and redness, skin rash (reddening of the skin), and itchy skin swellings.
• severe allergic reactions, including anaphylaxis (weakness, drop in 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 feel pain in the upper left part of the abdomen or left shoulder, as this may indicate spleen problems.
• breathing problems. If you have cough, fever, and difficulty breathing, contact your doctor.
• cases of Sweet’s syndrome (purple-colored, raised and painful skin lesions on the limbs, and sometimes on the face and neck, associated with fever) have been reported, although other factors may have contributed.
• cutaneous vasculitis (inflammation of the blood vessels in the skin).
• damage to the tiny filters within the kidneys (glomerulonephritis).
• redness at the injection site.
• coughing up blood (haemoptysis).
• blood disorders (myelodysplastic syndrome [MDS] or acute myeloid leukaemia [AML]).

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

• 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 lungs (pulmonary haemorrhage).
• Stevens-Johnson syndrome, which may present as reddish or roundish patches, often with central blisters, located on the trunk, skin peeling, mouth ulcers, and ulcers in the throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. If you develop these symptoms, stop using Ziextenzo and contact your doctor or seek immediate medical help. See also section 2.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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./EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C).
You may remove Ziextenzo from the refrigerator and keep it at room temperature (not above 35 °C) for up to
120 hours. Once the syringe has been removed from the refrigerator and has reached room temperature (not
above 35 °C), it must be used within 120 hours or must be discarded.
Do not freeze. Ziextenzo may be used if it has been accidentally frozen once for less than 24 hours.
Keep the container in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that it is cloudy or if particles are visible.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ziextenzo contains

• 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 (E420), polysorbate 20, sodium hydroxide and water for injections. See section 2 “Ziextenzo contains sorbitol (E420) and sodium”.

Description of the appearance of Ziextenzo 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 pre-filled glass syringe with a rubber plunger stopper (bromobutyl rubber, latex-free), a plunger rod, a 29-gauge stainless steel needle attached and a needle cap (thermoplastic elastomer, latex-free). The syringes are supplied with an automatic needle protection device.

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

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa
Тел.: +359 2 970 47 47 Tél/Tel: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf: +45 63 95 10 00 Tel: +35699644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz farmacevtska družba d.d.
Sandoz d.o.o.
Tel: +386 1 580 29 02
Tel: +385 1 23 53 111

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 20 0600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
Sandoz Pharmaceuticals d.d. Sandoz GmbH
Τηλ: +357 22 69 0690 Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

Instructions for Use of Ziextenzo Prefilled Syringe with Needle Protection

To help prevent possible infections and ensure correct use of the medicine, it is important
that you follow these instructions.
Read ALL instructions completely before administering your injection. It is important that you do not attempt to
administer the injection yourself unless you have been properly trained by your doctor, nurse, or pharmacist.
The package contains a single prefilled syringe sealed individually in a plastic blister.

Ziextenzo Prefilled Syringe with Needle Protection

After the medicine has been injected, the needle safety device will automatically activate to cover
the needle. The needle protection is designed to protect healthcare providers, caregivers, and patients
from accidental needlestick injuries after injection.

Additional Supplies Needed for Injection:

• Alcohol swab
• Cotton ball or gauze pad
• Sharps disposal container

Important Safety Information
Caution: Keep the prefilled syringe out of sight and reach of children.

1. Do not open the box until you are ready to use the prefilled syringe.
2. Do not use the prefilled syringe if the blister seal is broken, as it may not be safe to use.
3. Do not use the prefilled syringe if there is liquid inside the blister. Do not use the prefilled syringe if the needle cap is missing or not securely attached. In any of these cases, return the entire product package to the pharmacy.
4. Never leave the prefilled syringe unattended where it could be tampered with by others.
5. Do not shake the prefilled syringe.
6. Be careful not to touch the wings of the needle safety device before use. Touching them may cause premature activation of the needle safety device.
7. Do not remove the needle cap until immediately before administering the injection.
8. The prefilled syringe is not reusable. Dispose of the syringe immediately after use in a sharps disposal container.
9. Do not use the syringe if it has fallen on a hard surface or has been dropped after removing the needle cap.

Storage of Ziextenzo Prefilled Syringe

1. Store the blister-packaged prefilled syringe in the original carton to protect the medicine from light.
2. Store in the refrigerator at a temperature between 2 °C and 8 °C. Do not freeze.
3. Before use, remove the prefilled 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 prefilled syringe after the expiry date stated on the carton or on the syringe label. If the syringe has expired, return the entire package to the pharmacy.

Injection Site

The injection site is the location on the body where you will administer the prefilled syringe.

• The recommended site is the front of the thighs. You may also use the lower abdominal area, but not the area within 5 centimeters around the navel.
• Choose a different site each time you administer an injection.
• Do not inject into areas where the skin is tender, bruised, red, scaly, or hardened. Avoid injecting into areas with scars or stretch marks.

If someone else is administering the injection, the outer upper arm may also be used.

Preparing Ziextenzo Prefilled Syringe for Use

1. Remove the carton containing the blister-packaged prefilled syringe from the refrigerator and leave it closed for approximately 15–30 minutes until it reaches room temperature.
2. When ready to use the prefilled syringe, open the blister and wash your hands thoroughly with soap and water.
3. Clean the injection site with an alcohol swab.
4. Remove the prefilled syringe from the blister by holding it in the center as shown below. Do not grasp the plunger. Do not grasp the needle cap.

5. Check that the transparent plastic needle shield is positioned over the glass syringe barrel. If the transparent needle shield covers the needle cap (as shown below), the syringe’s needle safety device has been activated. DO NOT USE this syringe; obtain a new one. The following image shows a syringe ready for use.

Activated Device – DO NOT USE

In this configuration, the needle safety device is ACTIVATED – DO NOT USE the prefilled syringe
Ready-to-Use Device
In this configuration, the needle safety device is NOT ACTIVATED and the prefilled syringe is ready for use

6. Inspect the prefilled syringe. The liquid should be clear, ranging in color from transparent to slightly yellowish. A small air bubble may be visible in the liquid. This is normal. Do not use the prefilled syringe if you notice particles and/or discoloration.
7. Do not use the syringe if it is damaged or activated. Return the Ziextenzo prefilled syringe and packaging to the pharmacy.

How to Use Ziextenzo Prefilled Syringe
1

Carefully remove the needle cap by pulling it straight off. Discard the needle cap. A small drop of liquid at the tip of the needle may be visible. This is normal.

Pinch the skin gently at the injection site and insert the needle as shown. Push the needle fully in to ensure the complete dose is administered.

Holding the prefilled syringe as shown, press the plunger slowly and fully until the plunger head is completely between the wings of the needle safety device.
Keep the plunger fully depressed while holding the syringe in place for 5 seconds.

Keep the plunger fully depressed while carefully removing the needle straight out from the injection site, then release the skin.

Slowly release the plunger and allow the syringe’s needle safety device to automatically cover the exposed needle.
A small amount of blood may appear at the injection site. You may apply a cotton ball or gauze pad to the site and press for 10 seconds. Do not rub the injection site. If needed, you may cover the injection site with an adhesive bandage.

For Healthcare Professionals Only

The trade name of the administered product must be clearly recorded in the patient’s medical record. Remove and retain the label from the prefilled syringe.
Rotate the plunger to position the label where it can be easily removed.

Disposal Instructions

Dispose of the used syringe in a sharps disposal container (a puncture-resistant, closable container).
Do not dispose of any medicine via wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer in use. This will help protect the environment.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.