Package Insert: Information for the User

Pelgraz 6 mg injectable solution in pre-filled syringe

pegfilgrastim

Read the entire package insert carefully before starting to use the medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may 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 are not listed in this package insert. See section 4.

Pelgraz contains the active ingredient pegfilgrastim. Pegfilgrastim is a protein produced by biotechnology in the bacteriumE. 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 may be caused by cytotoxic chemotherapy (medicines that destroy rapidly dividing cells). White blood cells are important cells that contribute to fighting infections. These cells are sensitive to the effects of chemotherapy, which can cause their number to decrease. If the white blood cell count drops too low, there may not be enough to fight off bacteria, which implies a higher risk of contracting an 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 that will help you fight off infections.

Do not use Pelgraz

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

Warnings and precautions

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

• you experience an allergic reaction that includes weakness, decreased blood pressure, difficulty breathing, facial swelling (anaphylaxis), redness and flushing, skin rash, and itching in areas of the skin.
• you have a latex allergy. The cap of the pre-filled syringe contains a latex derivative that may 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 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 fatigue.

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

• if you have pain in the upper left abdominal area or pain in the shoulder tip. This may be a sign of a spleen problem (splenomegaly).
• you 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 alteration in your blood cell count (e.g., an increase in white blood cells or anemia) or a decrease in your platelet count, which may reduce your blood's ability to clot (thrombocytopenia). Your doctor may want to monitor you more closely.
• you have sickle cell anemia. Your doctor may closely monitor your condition.
• if you are a breast cancer or lung cancer patient, the combined treatment of Pelgraz with chemotherapy and/or radiation therapy may increase the risk of developing a pre-cancerous hematological condition called myelodysplastic syndrome (MDS) or a hematological malignancy called acute myeloid leukemia (AML). Symptoms may include fatigue, fever, easy bruising, or bleeding.
• you experience sudden signs of allergy, such as skin rash, itching, or urticaria, facial swelling, lip, tongue, or other body part swelling, shortness of breath, wheezing, or difficulty breathing, which may be signs of a severe allergic reaction.
• symptoms of aorta inflammation (the large blood vessel that carries blood from the heart to the body), which is rarely 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). Inform your doctor if you experience these symptoms.

Your doctor will perform regular blood and urine tests since Pelgraz may damage the small filters within your 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 consult with your doctor about the risk of developing blood cancer. If you develop or may develop blood cancer, do not use Pelgraz, except if your doctor advises you to.

Loss of response to pegfilgrastim

If you experience a loss of response or if you are unable to maintain 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 have not yet been established in children and adolescents. Consult your doctor or pharmacist before taking any medication.

Other medications and Pelgraz

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication. Pelgraz has not been used in pregnant women. It is essential to inform your doctor if:

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

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

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

Driving and operating machines

Pelgraz has no or negligible influence on your ability to drive and operate machines.

Pelgraz contains sorbitol (E420) and sodium

This medication contains 30 mg of sorbitol in the pre-filled syringe, equivalent to 50 mg/ml.

This medication contains less than 1 mmol of sodium (23 mg) per 6 mg dose; this is essentially "sodium-free".

Pelgraz is indicated in patients aged 18 years or older.

Follow exactly the administration instructions of Pelgraz indicated by your doctor. Consult with your doctor or pharmacist if you have doubts. The usual dose is a subcutaneous injection of 6 mg (under the skin), with a preloaded injector, which must be administered at the end of each chemotherapy cycle from 24 hours after your last chemotherapy dose.

Do not shake Pelgraz strongly as it may affect its activity.

Pelgraz Self-Administration

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

The instructions on how to administer Pelgraz yourself are below, but the correct treatment of your disease requires the close and constant cooperation of your doctor.

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

How do I administer the Pelgraz injection myself?

You will have to administer the injection into the tissue under the skin. This is what is called a subcutaneous injection.

Equipment you need

To administer a subcutaneous injection yourself, you will need:

• a preloaded injector of Pelgraz;
• alcohol swab.

What should I do before administering a subcutaneous injection of Pelgraz?

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

How do I prepare my Pelgraz injection?

Before injecting Pelgraz, you should do the following:

• Choose a clean, well-lit area to administer the medication.
• Check the expiration date on the packaging. Do not use it if it has passed the expiration date.
• Gather an alcohol swab and a sharps container

Remember

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

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-administering 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 other questions about the use of this medication, ask your doctor or pharmacist.

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

Inform your doctor immediately if you experience any of the following side effects:

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

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

Very common side effects(can affect more than 1 in 10 patients):

• bone pain. Your doctor will inform you about what you can take to alleviate the pain.

• nausea and headache.

Common side effects(can 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.

• you may experience some changes in your blood, which will be detected through periodic blood tests. You may have an increase in white blood cells for a short period of time. You may have a decrease in platelets, which can cause bruising.

Uncommon side effects(can affect up to 1 in 100 patients):

• allergic reactions, which include redness and flushing/flushes, appearance of hives, and skin inflammation with itching.
• severe allergic reactions, which include anaphylaxis (weakness, fall in blood pressure, difficulty breathing, facial swelling).

• enlargement of the spleen.

• spleen rupture. Some cases of spleen rupture were fatal. It is essential that you contact your doctor immediately if you notice pain in the upper left abdomen or left shoulder, as it 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 syndrome (painful, inflamed, violaceous lesions on the extremities and, in some cases, on the face and neck, accompanied by fever) have been reported, but may be related to other factors.

• cutaneous vasculitis (inflammation of skin blood vessels).

• damage to the small filters within the kidneys (glomerulonephritis).

• redness at the injection site.

• abnormal results from blood tests (lactate dehydrogenase, uric acid, and alkaline phosphatase).
• abnormal results from blood tests related to the liver (alanine aminotransferase, aspartate aminotransferase).
• coughing up blood (hemoptysis).
• hematological disorders (myelodysplastic syndrome [MDS] or acute myeloid leukemia [AML]).

Rare side effects (can affect 1 in 1,000 people):

• aortic inflammation (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 can appear as red spots with a target-like appearance or circular, 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 of 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 about 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. The expiration date is the last day of the month indicated.

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

Pelgraz can 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 must be discarded. For all doubts about storage, ask your doctor, nurse, or pharmacist.

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

Store the preloaded syringe in the box to protect it from light.

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

Medicines should not be thrown away 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.

• 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), polisorbate 20 and water for injection. (See section 2).

Appearance of the product and contents of the pack

Pelgraz is a clear, colourless injectable solution in a pre-filled syringe with a needle for injection. Each pre-filled syringe contains 0.6 ml of solution.

Pelgraz is available in a pack containing 1 pre-filled syringe, in an individual carton and an alcohol swab.

Marketing authorisation holder and responsible person for manufacturing

Marketing authorisation holder

Accord Healthcare S.L.U.

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

Edifici Est 6th floor,

08039 Barcelona,

Spain

Responsible person for manufacturing

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 authorisation 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

Revision date of this leaflet:06/2023

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

This information is intended solely for doctors or healthcare professionals:

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

Do not freeze. Accidental exposure to freezing temperatures for up to 24 hours does not affect the stability of Pelgraz. If exposure has been for more 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 pre-filled syringe administered should be clearly recorded in the patient's file.

Elimination

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