Azacitidine Sandoz

Leaflet accompanying the packaging: patient information

Azacitidine Sandoz, 100 mg, powder for suspension for injection

Azacitidine

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

• Keep this leaflet, so you can read it again if you need to.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

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

What is Azacitidine Sandoz

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

What is Azacitidine Sandoz used for

Azacitidine Sandoz is used in adults who cannot receive a stem cell transplant to treat:

• myelodysplastic syndromes (MDS) with a high risk;
• chronic myelomonocytic leukemia (CMML)
• acute myeloid leukemia (AML)

These are diseases that affect the bone marrow and can cause problems with the normal production of blood cells.

How Azacitidine Sandoz works

Azacitidine Sandoz works by preventing the growth of cancer cells. Azacitidine is incorporated into the genetic material of cells (RNA and DNA). It is thought that its action involves changing the way genes are activated and deactivated, and disrupting the production of RNA and DNA. It is believed that these actions correct the disturbances in the maturation and growth of young blood cells in the bone marrow, causing myelodysplastic disorders, and that they kill cancer cells in leukemia. If you have any questions about how Azacitidine Sandoz works or why it has been prescribed, consult your doctor or nurse.

2. Important information before using Azacitidine Sandoz

When not to use Azacitidine Sandoz

Warnings and precautions

Before starting treatment with Azacitidine Sandoz, discuss it with your doctor, pharmacist, or nurse if you have:

• a low platelet count, red blood cells, or white blood cells;
• kidney disease;
• liver disease
• a history of heart disease or heart attack, or any lung disease.

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

Children and adolescents

Azacitidine Sandoz should not be used in children and adolescents under 18 years of age.

Azacitidine Sandoz and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. Azacitidine Sandoz may affect the way some other medicines work. Some other medicines may also affect the way Azacitidine Sandoz works.

Pregnancy, breastfeeding, and fertility

Pregnancy Do not use Azacitidine Sandoz during pregnancy, as it may harm the baby. Women who can become pregnant should use effective contraception during treatment with Azacitidine Sandoz and for 6 months after stopping treatment with Azacitidine Sandoz. If you become pregnant during treatment, consult your doctor immediately. 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 Sandoz. It is not known if this medicine passes into breast milk. Fertility Men should not father a child during treatment with Azacitidine Sandoz. Men should use effective contraception during treatment with Azacitidine Sandoz and for 3 months after stopping treatment with this medicine. Consult your doctor before starting treatment if you want to store sperm.

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 Sandoz

Before administering Azacitidine Sandoz 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 decide on the dose based on the patient's overall condition, height, and weight. The doctor will monitor progress and may change the dose if necessary.
• Azacitidine Sandoz is given daily for one week, followed by a 3-week break. This treatment cycle is repeated every 4 weeks. Patients usually receive at least 6 treatment cycles.

This medicine 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 questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

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

• Drowsiness, tremors, jaundice, abdominal distension, and easy bruising.These may be symptoms of liver failure and can be life-threatening.
• Swelling of the legs and feet, back pain, decreased urine output, increased thirst, fast 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 and 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)

• Decreased red blood cell count (anemia). You may feel tired and pale.
• Decreased white blood cell count. This may be accompanied by fever. You are also more susceptible to infections.
• Low platelet count (thrombocytopenia). You are more prone 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.
• Purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Sleep disorders (insomnia).
• Nosebleeds.
• Muscle pain.
• Weakness.
• Weight loss.
• Low potassium levels in the blood.

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

• Bleeding in the skull.
• 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 count of red and white blood cells and platelets.
• A type of anemia where the count of red and white blood cells and platelets is reduced.
• 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.
• Mouth or tongue ulcers.
• Skin changes at the injection site. These include swelling, hard lumps, bruising, bleeding in the skin (hematomas), rash, itching, and skin discoloration.
• Redness of the skin.
• Skin infection (cellulitis).
• Nose and throat infection or sore throat.
• Nose or sinus pain (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath when moving.
• Throat and larynx pain.
• Nausea.
• Indifference.
• General malaise.
• 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, lethargy.
• Bleeding at the catheter insertion site.
• A disease of the intestines that 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 accumulation around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Large, raised, painful spots of a plum color on the skin, with fever.
• Inflammation of the membrane surrounding the heart (pericarditis).

Rare side effects(may affect up to 1 in 1000 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 breakdown 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 disturbances, seizures, and sometimes death.

Frequency not known(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 any side effects not listed in the leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration 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 Sandoz

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 after EXP. The expiry date refers to the last day of the month. The doctor, pharmacist, or nurse is responsible for storing Azacitidine Sandoz. They are also responsible for preparing Azacitidine Sandoz and disposing of any unused remains. Unopened vials of the medicine: There are no special storage instructions. For immediate useAfter preparation, the suspension should be administered within 60 minutes. For later useIf the Azacitidine Sandoz suspension was prepared using uncooled water for injections, the prepared suspension should be stored in the refrigerator (2°C - 8°C) immediately after preparation and kept in the refrigerator for no longer than 24 hours. If the Azacitidine Sandoz suspension was prepared using cooled (2°C - 8°C) water for injections, the prepared suspension should be stored in the refrigerator (2°C - 8°C) immediately after preparation and kept in the refrigerator for no longer than 36 hours in the vial and 30 hours in the syringe at 2°C - 8°C. Before administration, allow the suspension to reach room temperature (20°C - 25°C) for up to 30 minutes. Do not use the medicine if the suspension contains large particles.

6. Contents of the pack and other information

What Azacitidine Sandoz contains

The active substance is azacitidine.

• 1 vial contains 100 mg of azacitidine. After preparation with 4 ml of water for injections, the suspension contains 25 mg/ml of azacitidine.
• The other ingredient is mannitol.

What Azacitidine Sandoz looks like and contents of the pack

Azacitidine Sandoz is a white powder for suspension for injection. The powder is in a glass vial with a rubber stopper and an aluminum seal with a plastic cap, containing 100 mg of azacitidine. The vial is packaged in a cardboard box. Pack size: 1 vial.

Marketing authorization holder and manufacturer

Marketing authorization holder Sandoz GmbH Biochemiestrasse 10 6250 Kundl Austria Manufacturer/Importer Pharmadox Healthcare Ltd KW20A Kordin Industrial Park Paola, PLA 3000 Malta Lek Pharmaceuticals d.d. Verovskova ulica 57 1526 Ljubljana Slovenia Salutas Pharma GmbH Otto-von-Guericke-Allee 1 39179 Barleben Germany

For more information about this medicine, contact:

Sandoz Polska Sp. z o.o. ul. Domaniewska 50 C 02-672 Warszawa tel. 22 209 70 00

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Netherlands Azacitidine Sandoz 25 mg/ml, powder for suspension for injection Austria Azacitidin Sandoz 25 mg/ml – Pulver zur Herstellung einer Injektionssuspension Belgium Azacitidin Sandoz 25 mg/ml poeder voor suspensie voor injectie Bulgaria Азацитидин Сандоз 25 mg/ml прах за инжекционна суспензия Czech Republic Azacitidin Sandoz Germany Azacitidin HEXAL 25 mg/ml Pulver zur Herstellung einer Injektionssuspension Denmark Azacitidine Sandoz Greece Azacitidine/Sandoz 25 mg/ml κόνις για ενέσιμο εναιώρημα Spain Azacitidina Sandoz 25mg/ml polvo para solucion inyectable EFG Finland Azacitidine Sandoz France AZACITIDINE SANDOZ 25 mg/ml poudre pour suspension injectable Croatia Azacitidin Sandoz 25 mg/ml prašak za suspenziju za injekciju Hungary Azacitidin Sandoz 25 mg/ml por szuszpenziós injekcióhoz Ireland Azacitidine Rowex 25 mg/ml Powder for suspension for injection Iceland Azacitidine Sandoz Italy Azacitidina Sandoz Norway Azacitidine Sandoz Poland Azacitidine Sandoz Portugal Azacitidina Sandoz Romania Azacitidină Sandoz 25 mg/ml pulbere pentru suspensie injectabilă Sweden Azacitidine Sandoz Slovenia Azacitidin Sandoz 25 mg/ml prašek za suspenzijo za injiciranje Slovakia Azacitidine Sandoz 25 mg/ml prášok na injekčnú suspenziu Ireland (Northern Ireland) Azacitidine Sandoz 25 mg/ml powder for suspension for injection Date of last revision of the leaflet:12/2023

Information intended for healthcare professionals only:

Recommendations for safe handling Azacitidine Sandoz 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 the proper handling and disposal of anti-cancer medicinal products. In case of contact with prepared azacitidine on the skin, wash it immediately with soap and water. In case of contact with mucous membranes, rinse them with water. Incompatibilities Do not mix this medicinal product with other medicinal products, except for those mentioned below (see "Preparation procedure"). Preparation procedure Azacitidine Sandoz should be prepared using water for injections. The shelf-life of the prepared medicinal product can be extended by preparing the product with cooled (2°C - 8°C) water for injections. Details of storage of the prepared product are given below.

• 1. Obtain the following products: Vial(s) of azacitidine, vial(s) of water for injections, non-sterile surgical gloves, alcohol swabs, 5 ml syringe(s) for injection with needle(s).
• 2. Draw 4 ml of water for injections into the syringe and ensure that the air has been removed from the syringe.
• 3. Insert the needle of the syringe containing 4 ml of water for injections through the rubber stopper of the vial of azacitidine, and then inject the water for injections 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 fluid level. Then, pull back the plunger to draw 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. Attach a new needle for subcutaneous injection (recommended 25 G) firmly 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. Up to 30 minutes before administration, leave the syringe filled with the prepared suspension to reach a temperature of approximately 20°C - 25°C. If more than 30 minutes have passed, discard the suspension and prepare a new dose. To resuspend, vigorously shake 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 prepared product For Azacitidine Sandoz prepared with uncooled water for injections, the chemical and physical stability of the prepared medicinal product has been demonstrated for 60 minutes at 25°C and for 24 hours at 2°C - 8°C, stored in the vial and syringe. The shelf-life of the prepared medicinal product can be extended by preparing the product with cooled (2°C - 8°C) water for injections. For Azacitidine Sandoz prepared with cooled (2°C - 8°C) water for injections, the chemical and physical stability of the prepared medicinal product has been demonstrated when stored at 2°C - 8°C for 36 hours in the vial and for 30 hours in the syringe at 2°C - 8°C. From a microbiological point of view, the prepared product should be used immediately. If not used immediately, the storage time and conditions before use are the responsibility of the user. The solution should not be stored for more than 24 hours at a temperature of 2°C to 8°C. Calculation of 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. Administration method Do not filter the suspension after preparation. The prepared Azacitidine Sandoz should be injected subcutaneously (insert the needle at an angle of 45 - 90°) using a 25 G 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. Any unused product or waste materials should be disposed of in accordance with local requirements.