Azacitidine Stada

Package Leaflet: Information for the User

Azacitidine STADA, 25 mg/mL, Powder for Suspension for Injection

Azacitidinum

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

Keep this package leaflet, you may need to read it again.
In case of any doubts, consult a doctor, pharmacist, or nurse.
If the patient experiences any side effects, including those not listed in this package leaflet, inform the doctor, pharmacist, or nurse.
See section 4.

Table of Contents of the Package Leaflet:

• 1. What is Azacitidine STADA and what is it used for
• 2. Important information before using Azacitidine STADA
• 3. How to use Azacitidine STADA
• 4. Possible side effects
• 5. How to store Azacitidine STADA
• 6. Contents of the pack and other information

1. What is Azacitidine STADA and what is it used for

What is Azacitidine STADA

Azacitidine STADA is an anti-cancer medicine belonging to a group of medicines called "antimetabolites". Azacitidine STADA contains the active substance azacitidine.

What is Azacitidine STADA used for

Azacitidine STADA is used in adults who are not eligible for stem cell transplantation to treat:

• high-risk myelodysplastic syndromes (MDS)
• chronic myelomonocytic leukemia (CMML)
• acute myeloid leukemia (AML)

These diseases affect the bone marrow and can cause problems with normal blood cell production.

How Azacitidine STADA works

Azacitidine STADA works by preventing the growth of cancer cells. Azacitidine is incorporated into the genetic material of cells [ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)]. It is thought to work by changing the way genes are activated and deactivated, as well as disrupting the production of RNA and DNA. It is believed that these actions repair the maturation and growth disorders of young blood cells in the bone marrow that cause myelodysplastic disorders and kill cancer cells in leukemia. If you have any questions about how Azacitidine STADA works or why it has been prescribed, ask your doctor or nurse.

2. Important information before using Azacitidine STADA

When not to use Azacitidine STADA

• if you are allergic (hypersensitive) to azacitidine or any of the other ingredients of this medicine (listed in section 6)
• if you have advanced liver cancer
• if you are breastfeeding

Warnings and precautions

Before starting treatment with Azacitidine STADA, discuss with your doctor, pharmacist, or nurse if you:

• have a low platelet, red blood cell, or white blood cell count
• have kidney disease
• have liver disease
• have a history of heart disease, heart attack, or any lung disease

Azacitidine STADA may cause a severe immune reaction called "differentiation syndrome" (see section 4).
Blood tests
Before starting treatment with Azacitidine STADA and at the beginning of each treatment period (so-called "cycle"), blood tests will be performed. The purpose of these tests is to check if you have a sufficient number of blood cells and if your liver and kidneys are working properly.

Children and adolescents

Azacitidine STADA is not recommended for use in children and adolescents under 18 years of age.

Azacitidine STADA and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Azacitidine STADA may affect the way some other medicines work. Also, some other medicines may affect the way Azacitidine STADA works.

Pregnancy, breastfeeding, and fertility

Pregnancy
Do not use Azacitidine STADA during pregnancy, as it may harm the baby. Women who can become pregnant should use effective contraception during treatment with Azacitidine STADA and for 6 months after stopping treatment with this medicine.
Tell your doctor immediately if you become pregnant during treatment with Azacitidine STADA.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, consult your doctor or pharmacist before using this medicine.
Breastfeeding
Do not breastfeed while using Azacitidine STADA. It is not known if this medicine passes into human milk.
Fertility
Men should not father a child during treatment with Azacitidine STADA. Men should use effective contraception during treatment with Azacitidine STADA and for 3 months after stopping treatment with Azacitidine STADA.
Consult your doctor if you wish to preserve sperm before starting this treatment.

Driving and using machines

If you experience side effects such as fatigue, do not drive, use tools, or operate machinery.

3. How to use Azacitidine STADA

Before administering Azacitidine STADA to the patient, the doctor will give another medicine to prevent nausea and vomiting at the start of each treatment cycle.

• The recommended dose is 75 mg per square meter of body surface area. The doctor will choose the correct dose of Azacitidine STADA for you, depending on your overall condition, height, and weight. The doctor will monitor your progress and may change the dose if necessary.
• Azacitidine STADA is given daily for one week, followed by a 3-week rest period. This "treatment cycle" is repeated every 4 weeks. You will usually receive at least 6 cycles of treatment.

Azacitidine STADA is given as a subcutaneous injection by a doctor or nurse.
It can be injected under the skin of the thigh, abdomen, or arm.
If you have any further doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Azacitidine STADA can cause side effects, although not everybody gets them.

Tell your doctor immediately if you notice any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and easy bruising.These may be symptoms of liver failure, which can be life-threatening.
• Swelling of the legs and feet, back pain, decreased urine output, increased thirst, rapid heartbeat, dizziness, and nausea, vomiting, or loss of appetite, as well as feelings of disorientation, anxiety, or fatigue.These may be symptoms of kidney failure, which can be life-threatening.
• Fever. The cause may be an infection due to a low white blood cell count, which can be life-threatening.
• Chest pain or shortness of breath, which may be accompanied by fever.The cause may be a lung infection called "pneumonia" and can be life-threatening.
• Bleeding. Such as blood in the stool due to bleeding in the stomach or intestine or bleeding in the head. These may be symptoms of a low platelet count.
• Difficulty breathing, swelling of the lips, itching, or rash.The cause may be an allergic reaction (hypersensitivity).

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

• Low red blood cell count (anemia). You may feel tired and pale.
• Low white blood cell count. This may be accompanied by fever. You are also more susceptible to infections.
• Low platelet count (thrombocytopenia). You are more susceptible to bleeding and bruising.
• Constipation, diarrhea, nausea, vomiting.
• Pneumonia.
• Chest pain, shortness of breath.
• Fatigue.
• Reaction at the injection site, including redness, pain, or skin reaction.
• Loss of appetite.
• Joint pain.
• Bruising.
• Rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Sleep disturbances (insomnia).
• Nosebleeds.
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

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

• Bleeding in the brain.
• Blood infection caused by bacteria (sepsis). The cause may be a low white blood cell count in the blood.
• Bone marrow failure. This can lead to a low number of red and white blood cells and platelets.
• A type of anemia where the number of red and white blood cells and platelets is low.
• Urinary tract infection.
• Viral infection causing cold sores.
• Bleeding gums, bleeding in the stomach or intestine, bleeding from the anus due to hemorrhoids (hemorrhoidal bleeding), eye bleeding, bleeding under the skin or in the skin (hematomas).
• Blood in the urine.
• Ulcers in the mouth or tongue.
• Skin changes at the injection site. These include swelling, hard lumps, bruising, bleeding in the skin (hematomas), rash, itching, and skin color changes.
• Redness of the skin.
• Skin infection (cellulitis).
• Nose and throat infection or sore throat.
• Nose or sinus pain, or sinusitis (sinus infection).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath when moving.
• Throat and larynx pain.
• Nausea.
• Numness.
• General feeling of being unwell.
• Anxiety.
• Disorientation.
• Hair loss.
• Kidney failure.
• Dehydration.
• White patches on the tongue, inside the cheeks, and sometimes on the palate, gums, and tonsils (oral thrush).
• Fainting.
• Drop in blood pressure when standing up (orthostatic hypotension), leading to dizziness when changing position to standing or sitting.
• Drowsiness.
• Bleeding at the injection site.
• A disease affecting the intestines, which can cause fever, vomiting, and abdominal pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• Muscle spasms.
• A raised, itchy rash on the skin (hives).
• Fluid around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Large, plum-colored, raised, painful spots on the skin, with fever.
• Painful skin ulcers (necrotizing fasciitis).
• Inflammation of the membrane surrounding the heart (pericarditis).

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

• Dry cough.
• Painless swelling of the fingertips (clubbing).
• Tumor lysis syndrome - a complication of metabolism that can occur during cancer treatment, as well as sometimes without treatment. These complications are caused by the product of dying cancer cells and can include: changes in blood chemistry; high levels of potassium, phosphorus, uric acid, and low levels of calcium leading to kidney problems, heart rhythm problems, seizures, and sometimes death.

Frequency not known(frequency cannot be estimated from the available data)

• Infection of the deep skin layers, which can spread quickly, causing skin and tissue damage, and can be life-threatening (necrotizing fasciitis).
• A severe immune reaction (differentiation syndrome), which can cause fever, cough, difficulty breathing, rash, decreased urine output, low blood pressure (hypotension), swelling of the hands or feet, and sudden weight gain.
• Inflammation of the blood vessels in the skin, which can lead to a rash (cutaneous vasculitis).

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Azacitidine STADA

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton.
The expiry date refers to the last day of the month.
Your doctor, pharmacist, or nurse is responsible for storing Azacitidine STADA. They are also responsible for preparing Azacitidine STADA and disposing of any unused remains properly.
Unopened vials of the medicine - no special storage precautions.
For immediate use
The prepared suspension should be administered within 60 minutes.
For later use
If the product was prepared with unchilled water for injection, the prepared suspension should be stored in the refrigerator (2°C–8°C) immediately after preparation and stored in the refrigerator for no more than 24 hours.
If the product was prepared with chilled (2°C–8°C) water for injection, the prepared suspension should be stored in the refrigerator (2°C–8°C) immediately after preparation and stored in the refrigerator for no more than 36 hours (in a vial) or 30 hours (in a syringe).
Allow the syringe filled with the prepared suspension to reach room temperature (20°C–25°C) for up to 30 minutes before administration. If more than 30 minutes have passed, discard the suspension and prepare a new dose.
If the suspension contains large particles, discard it.

6. Contents of the pack and other information

What Azacitidine STADA contains

The active substance is azacitidine. One vial contains 100 mg of azacitidine. After reconstitution with 4 mL of water for injection, the reconstituted suspension contains 25 mg/mL of azacitidine.
Excipient: mannitol.

What Azacitidine STADA looks like and contents of the pack

Azacitidine STADA is a white powder for suspension for injection and is supplied in a clear, colorless glass vial (Type I) with a capacity of 30 mL, containing 100 mg of azacitidine. The vials may be packaged in protective polypropylene vials or directly packaged in a clean cardboard box.
Each pack contains one vial of Azacitidine STADA.

Marketing authorization holder and manufacturer

Marketing authorization holder:

STADA Arzneimittel AG
Stadatrasse 2-18
61118 Bad Vilbel
Germany

Manufacturer/Importer:

Pharmadox Healthcare Ltd
KW20A Kordin Industrial Park
Paola, PLA3000
Malta
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Czech Republic
AZACITIDIN STADA Arzneimittel AG
Hungary
Azacitidine Stada Arzeimittel 25 mg/mL por szuszpenziós injekcióhoz
Netherlands
Azacitidine STADA Arzneimittel 25 mg/mL, poeder voor suspensie voor injectie
Poland
Azacitidine STADA
Romania
AZACITIDINA STADA 25mg/mL pulbere pentru suspensie injectabilă
Slovakia
Azacitidine STADA Arzneimittel
Bulgaria
Azacitidine STADA Arzneimittel 25 mg/mL powder for suspension for injection

Date of last revision of the package leaflet: 02/2024

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Information intended for healthcare professionals only:

Recommendations for safe handling
Azacitidine STADA is a cytotoxic medicinal product, and as with other potentially toxic compounds, caution should be exercised when handling the azacitidine suspension. Follow the procedures for proper handling and disposal of anti-cancer medicinal products.
In case of contact with the prepared azacitidine, wash the skin immediately with soap and water. In case of contact with mucous membranes, rinse them thoroughly with water.
Incompatibilities
The medicinal product should not be mixed with other medicines, except for those listed below (see "Preparation procedure").
Preparation procedure
Azacitidine STADA should be prepared with water for injection. The shelf-life of the prepared medicinal product can be extended by dissolving the product with chilled (2°C–8°C) water for injection.
Details on storage of the prepared product are given below.

• 1. Obtain the following products: vial(s) of azacitidine, vial(s) of water for injection, non-sterile surgical gloves, alcohol swabs, 5 mL syringe(s) for injection with needle(s).
• 2. Draw 4 mL of water for injection into the syringe. Ensure that the air has been removed from the syringe.
• 3. Insert the needle of the syringe containing 4 mL of water for injection through the rubber stopper of the azacitidine vial and then slowly inject the water for injection into the vial.
• 4. After removing the syringe and needle, vigorously shake the vial until a uniform, cloudy suspension is obtained. After preparation, each mL of suspension contains 25 mg of azacitidine (100 mg/4 mL). The prepared product is a uniform, cloudy suspension without agglomerates. Discard the suspension if it contains large particles or agglomerates. Do not filter the suspension after preparation, as this may remove the active substance. Note that some adapters, needles, and closed systems contain filters. Therefore, such components should not be used to administer the medicinal product after preparation.
• 5. Clean the rubber stopper and insert a new needle with a syringe into the vial. Then, turn the vial upside down, ensuring that the needle tip is below the level of the liquid. Draw the plunger to withdraw the required amount of medicinal product for the correct dose. Ensure that the air has been removed from the syringe. Then, withdraw the needle with the syringe from the vial and discard the needle.
• 6. Firmly attach a new injection needle (recommended 25 G) to the syringe. Do not flush the needle before injection to reduce the frequency of local reactions at the injection site.
• 7. If more than 1 vial is needed, repeat all the above steps to prepare the suspension. For doses requiring more than 1 vial, divide the dose evenly, e.g., 150 mg dose = 6 mL, 2 syringes with 3 mL each. Due to retention in the vial and needle, it may not be possible to withdraw the entire suspension from the vial.
• 8. The contents of the syringe with the dose must be resuspended immediately before administration. The temperature of the suspension at the time of injection should be around 20°C–25°C. To resuspend, vigorously rotate the syringe between your hands until a uniform, cloudy suspension is obtained. Discard the suspension if it contains large particles or agglomerates.

Storage of the product after preparation
For immediate use
The Azacitidine STADA suspension can be prepared immediately before use, and the prepared suspension should be administered within 60 minutes. If more than 60 minutes have passed, discard the prepared suspension and prepare a new dose.
For later use
If the product was prepared with unchilled water for injection, the prepared suspension should be stored in the refrigerator (2°C–8°C) immediately after preparation and stored in the refrigerator for no more than 24 hours. If more than 24 hours of refrigerated storage have passed, discard the suspension and prepare a new dose.
If the product was prepared with chilled (2°C–8°C) water for injection, the prepared suspension should be stored in the refrigerator (2°C–8°C) immediately after preparation and stored in the refrigerator for no more than 36 hours (in a vial) or 30 hours (in a syringe). If the refrigerated storage time is longer than 36 hours (in the case of storage in a vial) or 30 hours (in the case of storage in a syringe), discard the suspension and prepare a new dose.
Allow the syringe filled with the prepared suspension to reach room temperature (20°C–25°C) for up to 30 minutes before administration. If more than 30 minutes have passed, discard the suspension and prepare a new dose.
Calculating the individual dose
The total dose can be calculated based on body surface area (BSA) as follows:
total dose = dose (mg/m²) x BSA (m²)
The following table is an example of how to calculate individual doses of azacitidine based on an average BSA of 1.8 m².

Method of administration
Do not filter the suspension after preparation.
The prepared Azacitidine STADA should be injected subcutaneously (insert the needle at an angle of 45-90°) using a 25 G injection needle in the arm, thigh, or abdomen.
Doses above 4 mL should be injected at two different sites.
Change the injection site. New injections should be given at least 2.5 cm from the previous site and never in sensitive, bruised, red, or hardened areas.
Dispose of any unused product or waste in accordance with local regulations.