PELGRAZ 6 mg INJECTABLE SOLUTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the User

Pelgraz 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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

1. What is Pelgraz and what is it used for

Pelgraz 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.

Pelgraz 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 cells that help fight infections. These cells are sensitive to the effects of chemotherapy, which can cause their numbers to decrease. If the number of white blood cells becomes too low, there may not be enough to fight off bacteria, which can lead to a higher risk of infection.

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

2. What you need to know before you use Pelgraz

Do not use Pelgraz

• if you are allergic to pegfilgrastim, filgrastim, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor, pharmacist, or nurse before using Pelgraz if:

• you experience an allergic reaction that includes weakness, decreased blood pressure, difficulty breathing, swelling of the face (anaphylaxis), redness and flushing, skin rash, and itching.
• you have a latex allergy. The needle cap of the pre-filled syringe contains a latex derivative that can cause severe allergic reactions.
• you experience cough, fever, and difficulty breathing. This may be a sign of Acute Respiratory Distress Syndrome (ARDS).
• you experience any or a combination of the following side effects:
• • swelling that may be associated with decreased urination frequency, difficulty breathing, swelling, and feeling of abdominal fullness and a general feeling of

fatigue.

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

• if you have pain in the upper left abdomen or pain in the tip of the shoulder. This may be a sign of a problem with the spleen (splenomegaly).
• you have recently had a severe lung infection (pneumonia), fluid in the lungs (pulmonary edema), inflammation of the lungs (interstitial lung disease), or an abnormal chest X-ray result (pulmonary infiltration).
• you are aware of any changes in your blood cell count (e.g., increased white blood cell count or anemia) or a decrease in your platelet count, which can reduce the ability of your blood to clot (thrombocytopenia). Your doctor may want to monitor you more closely.
• you have sickle cell anemia. Your doctor may monitor your condition more closely.
• you are a cancer patient with breast or lung cancer, the combined treatment of Pelgraz with chemotherapy and/or radiotherapy may increase the risk of developing a pre-cancerous hematological disorder called myelodysplastic syndrome (MDS) or a hematological malignancy called acute myeloid leukemia (AML). Symptoms may include fatigue, fever, easy bruising or bleeding.
• you have signs of a sudden allergic reaction, 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, may be signs of a severe allergic reaction.
• Symptoms of inflammation of the aorta (the large blood vessel that carries blood from the heart to the body), this has rarely been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general discomfort, back pain, and elevated inflammatory markers (e.g., C-reactive protein and white blood cell count). Tell your doctor if you experience these symptoms.

Your doctor will perform regular blood and urine tests since Pelgraz may damage the small filters within the kidneys (glomerulonephritis).

Severe skin reactions (Stevens-Johnson syndrome) have been reported with the use of Pelgraz. Stop using Pelgraz and seek medical attention immediately 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 develop or may develop blood cancer, you should not use Pelgraz, unless your doctor advises you to.

Loss of response to pegfilgrastim

If you experience a loss of response or if you do not achieve a response to treatment with pegfilgrastim, your doctor will investigate the causes, including whether you have developed antibodies that may neutralize the activity of pegfilgrastim.

Children and adolescents

The safety and efficacy of Pelgraz in children and adolescents have not been established. Consult your doctor or pharmacist before taking any medicine.

Other medicines and Pelgraz

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine. Pelgraz 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 plan to become pregnant.

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

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

Driving and using machines

Pelgraz has no or negligible influence on the ability to drive and use machines.

Pelgraz contains sorbitol (E420) 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; this is essentially "sodium-free".

3. How to use Pelgraz

Pelgraz is indicated in patients over 18 years of age.

Follow the instructions for administration of Pelgraz exactly as prescribed by your doctor. Consult your doctor or pharmacist if you have any doubts. The usual dose is a single subcutaneous injection of 6 mg (under the skin), with a pre-filled syringe, which should be administered at the end of each chemotherapy cycle, at least 24 hours after your last dose of chemotherapy.

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

Self-injection of Pelgraz

Your doctor may consider it more convenient for you to inject Pelgraz yourself. Your doctor or nurse will teach you how to do this. Do not attempt to do this unless you have received special training from your doctor or nurse.

The instructions for self-injection of Pelgraz are below, but the correct treatment of your condition requires close and constant cooperation with your doctor.

If you are unsure about how to administer the injection or have any doubts, ask your doctor or nurse for help and information.

How do I give myself a Pelgraz injection?

You will need to inject the medicine into the tissue under the skin. This is called a subcutaneous injection.

Equipment needed

To give yourself a subcutaneous injection, you will need:

• a pre-filled syringe of Pelgraz;
• alcohol swab.

What should I do before giving myself a subcutaneous injection of Pelgraz?

1. Take the pre-filled syringe out of the refrigerator.
2. Do not remove the needle cap from the syringe until you are ready to inject.
3. Check the expiration date on the label of the pre-filled syringe (EXP). Do not use it if it has passed the last day of the month indicated or if it has been stored out of the refrigerator for more than 15 days or is expired.
4. Check the appearance of Pelgraz. It should be a clear, colorless liquid. Do not use it if there are particles.
5. To make the injection more comfortable, let the pre-filled syringe sit at room temperature for 30 minutes or hold the pre-filled syringe gently in your hand for a few minutes. Do not heat Pelgraz in any other way (e.g., do not heat it in the microwave or in hot water).
6. Wash your hands carefully.
7. Find a comfortable, well-lit place and put everything you need within reach (the pre-filled syringe and the alcohol swab).

How do I prepare my Pelgraz injection?

Before injecting Pelgraz, you must do the following:

Never use a pre-filled syringe that has been dropped onto a hard surface.

Step 1: Check the integrity of the system

1. Make sure the system is intact and not damaged. Do not use the medicine if it appears damaged (if the syringe or needle cap is broken) or has loose components, or if the needle cap is in the open position as shown in Image 9, because this indicates that the system has already been activated. In general, the medicine should not be used if it does not match Image 1. If so, the medicine should be discarded in a container for disposing of hazardous biological waste.

Image 1

Step 2: Remove the needle cap

1. Remove the needle cap as shown in Image 2. Hold the needle cap with one hand, with the needle pointing away from you and without touching the plunger rod. Remove the needle cap with the other hand. After doing so, discard the needle cap in a container for disposing of hazardous biological waste.
2. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before injection. Injecting the solution with an air bubble is not harmful.
3. The pre-filled syringe is now ready to use.

Image 2

Where should I inject myself?

The best places to inject are:

• the top of the thighs, and
• the abdomen, except for the area around the navel (see Image 3).

Image 3

If someone else is going to give you the injection, they can also use the back of the arms (see Image 4)

Image 4

It is best to change the injection site each time to avoid the risk of pain at one site.

How do I give myself the injection?

Disinfect the injection site using an alcohol swab and pinch the skin between your thumb and index finger without squeezing it (see Image 5).

Image 5

Step 3: Insert the needle

• Pinch the skin lightly at the injection site with one hand;
• With the other hand, insert the needle into the injection site at an angle of 45-90 degrees (see Images 6 and 7).

Image 6

Image 7

Pre-filled syringe with needle safety guard

• Insert the needle fully into the skin as shown by your nurse or doctor (see Image 6).
• Gently pull back on the plunger to check if you have accidentally injected into a blood vessel. If you see blood in the syringe, remove the needle and insert it into another location.
• Inject only the dose that your doctor has prescribed, following the instructions below.

Stage 4: Injection

Place your thumb on the end of the plunger. Press the plunger rod and push firmlyto ensure that the syringe is empty (see Image 8). Hold the skin firmly until the injection is complete.

Image 8

Step 5: Protection against accidental needle sticks

The safety system is activated when the plunger is pushed to the end:

• Without moving the syringe, slowly lift your thumb off the end of the plunger;
• The plunger will rise with your thumb, and the spring will retract the needle from the injection site into the needle safety guard (see Image 9).

Image 9

Remember

If you have any problems, ask your doctor or nurse for help and information.

Disposal of used syringes

Dispose of the syringe as instructed by your doctor, pharmacist, or nurse.

If you use more Pelgraz than you should

If you use more Pelgraz than you should, contact your doctor, pharmacist, or nurse.

If you forget to use Pelgraz

If you are self-injecting and have forgotten to administer your dose of Pelgraz, contact your doctor to decide when you should inject the next dose.

If you stop using Pelgraz

Your doctor will tell you when to stop using Pelgraz. It is quite normal to have a series of treatment cycles with Pelgraz.

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

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

Immediately inform your doctor if you experience any or a combination of the following adverse effects:

• Swelling that may be associated with urinating less frequently, difficulty breathing, swelling, and a feeling of abdominal fullness and a general feeling of tiredness. These symptoms usually develop very quickly.

These may be symptoms of a disease that occurs infrequently (which may affect up to 1 in 100 people) called "capillary leak syndrome" and may cause blood to leak from a small blood vessel to other parts of your body and require urgent medical attention.

Very Common Adverse Effects(may affect more than 1 in 10 patients):

• Bone pain. Your doctor will inform you about what you can take to calm the pain.

• Nausea and headache.

Common Adverse Effects(may affect up to 1 in 10 patients):

• Pain at the injection site.

• General pain and pain in the joints and muscles.

• Chest pain not caused by heart disease or heart attack.

• Some changes may occur in your blood, which will be detected through periodic blood tests. The number of white blood cells may increase for a short period. The number of platelets may decrease, which can cause bruising.

Uncommon Adverse Effects(may affect up to 1 in 100 patients):

• Allergic reactions, including redness and flushing, rash, and skin inflammation with itching.
• 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 were fatal. It is essential that you contact your doctor immediately if you notice pain in the upper left part of your abdomen or in the left shoulder, as they may be related to a problem with your spleen.

• Respiratory problems. If you have a cough, fever, and difficulty breathing, consult your doctor.
• Cases of Sweet's syndrome (painful, inflamed, purple-colored lesions on the extremities and sometimes on the face and neck, accompanied by fever) have occurred, but may be related to other factors.

• Cutaneous vasculitis (inflammation of the skin blood vessels).

• Damage to the small filters inside the kidneys (glomerulonephritis).

• Redness at the injection site.

• Abnormal blood test results (lactate dehydrogenase, uric acid, and alkaline phosphatase).
• Abnormal blood test results related to the liver (alanine aminotransferase, aspartate aminotransferase).
• Coughing up blood (hemoptysis).
• Hematological disorders (myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML]).

Rare Adverse Effects (may affect 1 in 1,000 people):

• Inflammation of the aorta (the large blood vessel that carries blood from the heart to the body) see section 2.
• Bleeding from the lung (pulmonary hemorrhage)
• Stevens-Johnson syndrome, which may appear as reddish spots with a target-like or circular appearance, often with central blisters on the trunk, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Stop using Pelgraz if you develop these symptoms and contact your doctor or seek immediate medical attention. See also section 2.

Reporting Adverse Effects

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

5. Storage of Pelgraz

Keep this medicine out of sight and reach of children.

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

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

Pelgraz may be at room temperature (not above 25°C ± 2°C) for a single period of up to 15 days. If Pelgraz is left at room temperature for more than 15 days, it should be discarded. For any doubts about storage, ask your doctor, nurse, or pharmacist.

Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours does not negatively affect the stability of Pelgraz.

Store the pre-filled syringe in the box to protect it from light.

Do not use this medicine if you observe that the solution is not totally transparent or contains particles.

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Pelgraz Composition

• The active ingredient is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 ml of solution.
• The other components are sodium acetate, sorbitol (E420), polysorbate 20, and water for injectable preparations. (See section 2).

Product Appearance and Package Contents

Pelgraz is a clear, colorless injectable solution in a pre-filled syringe with a safety needle guard. Each pre-filled syringe contains 0.6 mg of solution.

Pelgraz is available in packages with 1 pre-filled syringe, with a pre-attached safety needle guard in a blister pack and an alcohol swab.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice, Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IS / LT / LV / LX/ MT / NL / NO / PT / PL / RO / SE / SI / SK / ES

Accord Healthcare S.L.U. Tel: +34 93 301 00 64

IT

Accord Healthcare Italia

Tel: +39 02 94323700

EL

Win Medica Pharmaceutical S.A.

Tel: +30 210 7488 821

Date of Last Revision of this Prospectus: 06/2023

Other Sources of Information

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

This information is intended only for doctors or healthcare professionals:

Pelgraz does not contain any preservative. Due to the possible risk of microbial contamination, Pelgraz syringes are for single use.

Do not freeze. Accidental exposure to freezing temperatures for up to 24 hours does not affect the stability of Pelgraz. If the exposure has been longer than 24 hours or has been frozen more than once, DO NOT use Pelgraz.

To improve the traceability of granulocyte colony-stimulating factors, the name of the medicine (Pelgraz) and the batch number of the administered syringe should be clearly recorded in the patient's file.

Use of the pre-filled syringe with safety needle guard

The safety needle guard covers the needle after injection to prevent needlestick injuries. This does not affect the normal functioning of the syringe. Press the plunger rod and push firmlyat the end of the injection to ensure that the syringe has been completely emptied. Hold the skin firmly until the injection is complete. Keep the syringe still and slowly lift your thumb from the plunger head. The plunger rod will move up with your thumb, and the spring will retract the needle from the site, within the safety needle guard.

Do not use a pre-filled syringe if it has been dropped onto a hard surface.

Disposal

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.