Dyrupeg

Package leaflet: Information for the user

Dyrupeg 6 mg solution for injection in pre-filled syringe

pegfilgrastim
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before 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 give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Dyrupeg is and what it is used for

Dyrupeg 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.
Dyrupeg 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), which may be caused by cytotoxic chemotherapy (drugs that destroy rapidly growing cells), in adults aged 18 years and older. 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 decrease 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 Dyrupeg to stimulate the bone marrow (the part of the bone that produces blood cells) to produce more white blood cells, helping your body to fight infections.

2. What you need to know before using Dyrupeg

Do not use Dyrupeg
 if you are allergic to pegfilgrastim, filgrastim, or to any of the other ingredients of this
medicinal product (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Dyrupeg:

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing, facial swelling (anaphylaxis), redness, skin rash, or itchy skin areas.
   if you have cough, fever, and difficulty breathing. These may be signs 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, a feeling of fullness, and general fatigue. These could be symptoms of a condition called "Capillary Leak Syndrome," which causes blood to leak from small blood vessels in the body. See section 4.
     if you have pain in the upper left part of the abdomen or shoulder tip pain. These may be signs of a spleen problem (splenomegaly).
     if you have recently had a severe lung infection (pneumonia), fluid in the lungs (pulmonary edema), lung inflammation (interstitial lung disease), or an abnormal X-ray finding (pulmonary infiltration).
     if you know you have abnormal blood cell counts (e.g., elevated white blood cells or anemia) or reduced platelet levels, which impair the body’s ability to clot (thrombocytopenia). Your doctor may wish to monitor you closely.
     if you have sickle cell anemia. Your doctor may wish to monitor you closely.
     if you have breast or lung cancer, Dyrupeg 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 leukemia (AML). Symptoms may include fatigue, fever, and easy bruising or bleeding.
     if you suddenly develop signs of allergy such as skin rash, hives, or itching, swelling of the face, lips, tongue, or other body parts, shortness of breath, wheezing, or difficulty breathing: these could be signs of a severe allergic reaction.
     Inflammation of the aorta (the large blood vessel carrying blood from the heart to the body) has been rarely reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Inform your doctor if you experience any of these symptoms.

Your doctor will regularly monitor your blood and urine, as Dyrupeg may damage the tiny filters in your kidneys (glomerulonephritis).
Severe skin reactions (Stevens-Johnson syndrome) have been observed with the use of Dyrupeg. If you notice any of the symptoms described in section 4, stop using Dyrupeg and seek immediate medical attention.
You should discuss with your doctor the risks of developing blood cancer. If you have or may have blood cancer, you must not use Dyrupeg unless specifically 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.

Children and adolescents
Dyrupeg is not recommended for use in children and adolescents due to insufficient data on safety and efficacy.

Other medicines and Dyrupeg
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Dyrupeg has not been studied in pregnant women. Therefore, your doctor may decide not to use this medicine. It is important that you inform your doctor if:
 you are pregnant;
 you suspect you are pregnant; or
 you are planning a pregnancy.
If you become pregnant while being treated with Dyrupeg, inform your doctor.
Unless otherwise instructed by your doctor, you must stop breastfeeding while using Dyrupeg.

Driving and using machines
Dyrupeg does not alter or alters negligibly the ability to drive vehicles or operate machinery.

Dyrupeg contains sorbitol (E420)
This medicinal product contains 30 mg of sorbitol per pre-filled syringe, equivalent to 50 mg/mL.

Dyrupeg contains sodium
This medicinal product contains less than 1 mmol (23 mg) of sodium per 6 mg dose, i.e., essentially “sodium-free.”

Dyrupeg contains polysorbate 20 (E432)
This medicinal product contains 0.02 mg of polysorbate 20 in each pre-filled syringe. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Dyrupeg

Use Dyrupeg exactly as your doctor has told you. If you have any doubts, consult your doctor or
pharmacist. The recommended dose is one subcutaneous injection (an injection under the skin) of 6 mg using
a pre-filled syringe, which must be administered at least 24 hours after the last dose of
chemotherapy at the end of each chemotherapy cycle.
How to self-administer the Dyrupeg injection
Your doctor may consider it appropriate for you to self-administer the Dyrupeg injection. Your doctor or
nurse will show you how to give yourself the Dyrupeg injection. Do not attempt to inject yourself unless
you have been properly instructed on how to do so.
Refer to the section at the end of this leaflet for instructions on how to self-administer the Dyrupeg injection.

Dyrupeg alone.

Do not shake Dyrupeg vigorously, as this may compromise its activity.
If you use more Dyrupeg than you should
If you use more Dyrupeg than you should, contact your doctor, pharmacist, or nurse.
If you forget an injection of Dyrupeg
If you perform self-injection and have missed a dose of Dyrupeg, contact your doctor to determine when to administer the next dose.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Inform your doctor immediately if you experience any one or a combination of the following side effects:
 swelling or oedema, which may be associated with reduced frequency of urination,
breathing difficulties, 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 pain and joint and muscle aches.
 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 hot flushes, skin rash (reddening of the skin), and itchy skin swellings.
 severe allergic reactions including anaphylaxis (weakness, drop in blood pressure, breathing difficulties, 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 side of your 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-coloured, raised and painful skin lesions on limbs and sometimes on face and neck, associated with fever), although other factors may have contributed.
 cutaneous vasculitis (inflammation of the skin blood vessels).
 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 lung (pulmonary haemorrhage).
 Stevens-Johnson syndrome, which may present as reddish patches or round spots, often with central blisters, located on the trunk, skin peeling, mouth ulcers, and sores in the throat, nose, genitals and eyes, and may be preceded by fever and flu-like symptoms. If you develop these symptoms, stop using Dyrupeg and contact your doctor or seek immediate medical assistance. 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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dyrupeg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the syringe after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C).
You may remove Dyrupeg from the refrigerator and store it at room temperature (not above 25 °C) for up to three days. Once a syringe has been removed from the refrigerator and has reached room temperature (not above 25 °C), it must be used within three days.
Do not freeze. Dyrupeg may still be used if it has been accidentally frozen once for less than 72 hours.
Keep the pre-filled syringe in its outer packaging to protect it 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Dyrupeg contains
 The active substance is pegfilgrastim. Each pre-filled syringe contains 6 mg of pegfilgrastim in 0.6 mL of solution.
 The other ingredients are sodium acetate, sorbitol (E420), polysorbate 20 (E432), and water for injections. See section 2, "Dyrupeg contains sorbitol (E420), polysorbate 20 (E432) and sodium".

Description of the appearance of Dyrupeg and contents of the pack
Dyrupeg is a clear, colourless injectable solution in a pre-filled syringe (6 mg/0.6 mL).
Each pack contains one pre-filled glass syringe with a rubber plunger stopper, a plunger rod, a fixed stainless steel needle, and a needle cap. The syringe is provided in a blister tray.
The syringe is supplied with an automatic needle protection device.

Marketing Authorisation Holder and Manufacturer
CuraTeQ Biologics s.r.o.,
Trtinova 260/1,
Prague, 19600,
Czech Republic

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

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

Instructions for use:

Parts Guide
Before use	After use
Plunger Base for finger support Label of the syringe Barrel of the syringe Safety shield of the syringe Safety spring of the needle Grey needle cap inserted	Used plunger Label of the syringe Used barrel of the syringe Used needle Used safety spring of the needle Grey needle cap removed
Caution: Avoid contact with the plunger and the needle during syringe preparation. The safety device is normally activated by pressure on the syringe plunger.

Important
Before using a pre-filled syringe of Dyrupeg with automatic needle protection device,
please read these important instructions:

• It is important that you do not attempt to perform the injection unless you have received adequate instructions from your doctor or healthcare professional.
• Dyrupeg is administered as an injection into the tissue just beneath the skin (subcutaneous injection). Do not remove the needle cap from the pre-filled syringe until you are ready to inject. Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare professional. Do not attempt to activate the pre-filled syringe before the injection. Do not attempt to remove the transparent safety shield from the pre-filled syringe. Do not attempt to remove the detachable label from the barrel of the pre-filled syringe before administering the injection.

Contact your doctor or healthcare professional if you have any questions.

Step 1: Preparation
A	Remove the pre-filled syringe from its packaging and gather the necessary materials for injection: alcohol swabs, a cotton ball or gauze, a bandage, and a sharps disposal container (not included).
For a more comfortable injection, allow the pre-filled syringe to reach room temperature for about 30 minutes before injecting. Wash your hands thoroughly with soap and water. Place the new pre-filled syringe and the required injection materials on a clean, well-lit work surface. Do not attempt to warm the syringe using a heat source such as hot water or a microwave oven. Do not expose the pre-filled syringe to direct sunlight. Do not shake the pre-filled syringe excessively. Keep the pre-filled syringe out of sight and reach of children.
B	Warning/Precaution: Check that there are no fragments or melted material inside the packaging. If in doubt, DO NOT open this package; instead, use another package.
C	Warning/Precaution: DO NOT lift the product by the plunger or needle cap. Hold the safety shield of the pre-filled syringe to remove the pre-filled syringe from the blister tray.
D	Remove the pre-filled syringe from the blister tray as illustrated.
Do not use the pre-filled syringe if: •The medicine is cloudy or contains particles. It should be a clear, colorless liquid. •Any parts appear cracked or broken. •The gray needle cap is missing or not securely attached. •The expiration date printed on the label has passed the last day of the month indicated. In any of these cases, contact your doctor or healthcare provider.
Medicine
Step 2: Preparation
A	Wash your hands thoroughly. Prepare and clean the injection site.
Upper arm Abdomen Upper thigh
You may use: •The upper thigh. •The abdomen, except for an area of 5 centimeters around the navel. •The outer upper arm (only if someone else is administering the injection). Clean the injection site with an alcohol swab. Allow the skin to dry. Do not touch the injection site before injecting. Do not inject into areas where the skin is tender, bruised, red, or hardened. Avoid injecting into areas with scars or stretch marks.
B	Carefully pull off the gray needle cap, moving it away from your body.
Warning/Precaution: DO NOT twist the needle cap and do not touch the needle or plunger. Remove the needle cap straight off as shown, and handle the safety shield to avoid injury or bending.
C	Lift the injection site to create a stable surface.
Warning/Precaution: It is important to keep the skin lifted during injection.
Step 3: Injection
A	Hold the skin lifted. INSERT the needle into the skin. Push the plunger down while holding the grips.
Warning/Precaution: Do not touch the cleaned area of the skin.
B	PUSH the plunger with slow, steady pressure until you feel or hear a "click". Push all the way until the click is heard. To activate the safety feature, the full dose must be administered.
Precaution: It is important to push all the way to the "click" to deliver the full dose. CLICK
C	RELEASE the thumb. Then REMOVE the syringe from the skin.
After releasing the plunger, the safety shield of the pre-filled syringe will automatically cover the injection needle securely. Warning/Precaution: Do not recap used pre-filled syringes. If the safety shield does not activate or only partially activates, discard the product—without replacing the needle cap.

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 prefilled syringe label.

Rotate the plunger to move the label to a position where it can be removed.

Step 4: Finish
A	Dispose of the used prefilled syringe and other materials in a sharps disposal container.

Medicines must be disposed of in accordance with local regulations. Ask your pharmacist
how to dispose of medicines you no longer use. These measures will help protect the environment.
Keep the syringe and the sharps disposal container out of sight and reach of children.
Warnings:
Do not reuse the pre-filled syringe.