Azacitidine Sandoz 25 mg/ml powder for injection solution EFG

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET

Package leaflet: information for the user

Azacitidine Sandoz 25 mg/ml powder for injectable suspension EFG

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is not a side effect listed in this leaflet. See section 4.

Contents of this leaflet

1. What Azacitidine Sandoz is and what it is used for
2. What you need to know 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 Azacitidina Sandoz is and what it is used for

What Azacitida Sandoz is

This medicine is an anticancer agent belonging to a group of medicines called "antimetabolites". This medicine contains the active substance "azacitidine".

What Azacitidina Sandoz is used for

Azacitidine is used in adults who cannot receive a stem cell transplant 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 in the normal production of blood cells.

How Azacitidina Sandoz works

Azacitidine 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 believed to act by altering the way cells turn genes on or off, through interference with the production of new RNA and DNA. These actions are thought to correct the problems in maturation and growth of healthy blood cells in the bone marrow caused by myelodysplastic disorders, and to kill cancer cells in leukemia.

Consult your doctor or nurse if you have any questions about how azacitidine works or why this medicine has been prescribed for you.

2. What you need to know before using Azacitidina Sandoz

Do not use Azacitidina Sandoz

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with azacitidine:

• If you have low platelet counts, red blood cells, or white blood cells.
• If you have kidney disease.
• If you have liver disease.
• If you have ever had heart disease or a myocardial infarction, or have a history of lung disease.

Azacitidine may cause a serious immune reaction called “differentiation syndrome” (see section 4).

Blood tests

Before starting treatment with azacitidine and at the beginning of each treatment period (called a “cycle”), you will have blood tests. These are performed to ensure that you have sufficient blood cells and that your liver and kidneys are functioning properly.

Children and adolescents

The use of azacitidine is not recommended in children and adolescents under 18 years of age.

Other medicines and Azacitidina Sandoz

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This is because azacitidine may affect how other medicines work. Likewise, other medicines may affect how azacitidine works.

Pregnancy, breastfeeding, and fertility

Pregnancy

You must not use azacitidine during pregnancy because it may harm the unborn baby.

If you are a woman of childbearing potential, you must use an effective method of contraception during treatment with azacitidine and for 6 months after stopping treatment with azacitidine.

Inform your doctor immediately if you become pregnant during treatment.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Breastfeeding

Azacitidina must not be used during breastfeeding. It is unknown whether this medicine is excreted in human milk.

Fertility

Men must not father a child while receiving treatment with azacitidine.

Men should use an effective method of contraception during treatment with azacitidine and for 3 months after stopping treatment with azacitidine.

Speak to your doctor if you wish to preserve your sperm before starting this treatment.

Driving and using machines

Do not drive or operate tools or machinery if you experience adverse effects such as fatigue.

3. How to use Azacitidine Sandoz

Before administering azacitidine, your doctor will give you another medicine to prevent nausea and vomiting at the beginning of each treatment cycle.

• The recommended dose is 75 mg/m2 body surface area. Your doctor will determine your dose of this medicine based on your general condition, height, and weight. Your doctor will monitor your progress and, if necessary, may adjust your dose.
• Azacitidine is administered daily for one week, followed by a three-week rest period. This “treatment cycle” will be repeated every four weeks. You will usually receive at least six treatment cycles.

A doctor or nurse will administer this medicine as an injection under the skin (subcutaneous route). It can be given under the skin of the thigh, abdomen, or upper arm.

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

4. Possible adverse effects

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

Immediately inform your doctor if you notice any of the following adverse effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and easy bruising. These may be symptoms of liver failure, which can be potentially fatal.
• Swelling of legs and feet, back pain, reduced urine output, increased thirst, rapid pulse, dizziness and nausea, vomiting or loss of appetite, and confusion, restlessness, or fatigue. These may be symptoms of kidney failure, which can be potentially fatal.
• Fever. This could be due to an infection resulting from low white blood cell counts, which can be potentially fatal.
• Chest pain or difficulty breathing, which may be accompanied by fever. This may be due to a lung infection known as "pneumonia" and can be potentially fatal.
• Bleeding. For example, blood in stools due to bleeding in the stomach or intestine, or bleeding inside the head. These may be symptoms of low platelet counts in the blood.
• Difficulty breathing, swelling of the lips, itching, or skin rash. These may be due to an allergic reaction (hypersensitivity).

Other adverse effects include:

Very common adverse effects (may affect more than 1 in 10 people)

• Decreased red blood cell count (anemia). You may feel tired and look pale.
• Decreased white blood cell count. This may be accompanied by fever. You are also more likely to develop infections.
• Low platelet count in the blood (thrombocytopenia). You are more prone to bleeding and bruising.
• Constipation, diarrhea, nausea, vomiting.
• Pneumonia.
• Chest pain, difficulty breathing.
• Tiredness (fatigue).
• Reaction at the injection site, including redness, pain, or a skin reaction.
• Loss of appetite.
• Joint pain.
• Bruising.
• Skin rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Trouble falling asleep (insomnia).
• Nosebleeds (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

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

• Bleeding inside the head.
• Blood infection caused by bacteria (sepsis). This may result from low white blood cell counts in the blood.
• Bone marrow failure. This may cause low levels of red and white blood cells and platelets.
• A type of anemia characterized by reduced red and white blood cells and platelets.
• Urinary tract infection.
• A viral infection causing herpes-like lesions.
• Bleeding from the gums, stomach or intestinal bleeding, bleeding in the back due to hemorrhoidal bleeding, bleeding in the eyes, bleeding under or into the skin (hematoma).
• Blood in the urine.
• Mouth or tongue ulcers.
• Skin changes at the injection site, including swelling, hard lump, bruising, bleeding into the skin (hematoma), rash, itching, and skin color changes.
• Skin redness.
• Skin infection (cellulitis).
• Nose and throat infection, or sore throat.
• Pain or excessive discharge from the nose or sinuses (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing during physical activity.
• Throat and larynx pain.
• Indigestion.
• Drowsiness (lethargy).
• Feeling unwell.
• Anxiety.
• Confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• White coating covering the tongue, inside of the cheeks, and sometimes the palate, gums, and tonsils (fungal infection in the mouth).
• Fainting.
• Drop in blood pressure upon standing (orthostatic hypotension), causing dizziness when standing up or sitting down.
• Sleepiness, drowsiness (somnolence).
• Bleeding from a catheter site.
• A condition affecting the intestine that may cause fever, vomiting, and stomach pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Tremors (chills).
• Muscle spasms.
• Itchy skin rash (urticaria).
• Fluid accumulation around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Painful, large, raised plum-colored spots on the skin and fever.
• Painful skin ulcers (pyoderma gangrenosum).
• Inflammation of the lining surrounding the heart (pericarditis).

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

• Dry cough.
• Painless swelling of the fingertips (clubbing).
• Tumor lysis syndrome – metabolic complications may occur during cancer treatment and sometimes even without treatment. These complications result from the breakdown products of dying tumor cells and may include: changes in blood biochemistry, high levels of potassium, phosphorus, uric acid, and low calcium levels, leading to changes in kidney function and heart rhythm, seizures, and sometimes death.

Frequency not known (cannot be estimated from available data)

• Severe skin infection affecting deep layers of the skin, spreading rapidly and damaging skin and tissue, which can be potentially fatal (necrotizing fasciitis).
• Severe immune reaction (differentiation syndrome) that may cause fever, cough, difficulty breathing, skin rash, reduced urine output, low blood pressure (hypotension), swelling of arms or legs, and rapid weight gain.
• Inflammation of blood vessels in the skin, which may cause skin rash (cutaneous vasculitis).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Azacitidine Sandoz

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 label of the vial after CAD/EXP. The expiry date refers to the last day of the month indicated.

Your doctor, pharmacist, or nurse is responsible for the storage of azacitidine, as well as for the proper preparation and disposal of unused medicine.

For unopened vials of this medicine:

This medicine does not require special storage conditions.

If used immediately

The suspension must be administered within 60 minutes of preparation.

If used later

If the azacitidine suspension is prepared using non-refrigerated water for injections, the suspension must be placed immediately in the refrigerator (between 2 °C and 8 °C) after preparation and may be stored in the refrigerator for up to 24 hours.

If the azacitidine suspension is prepared using water for injections that has been refrigerated (between 2 °C and 8 °C), the suspension must be placed immediately in the refrigerator (between 2 °C and 8 °C) after preparation and may be stored in the refrigerator for up to 36 hours when kept in the vial, or up to 30 hours between 2 °C and 8 °C when stored in a syringe.

The suspension should be allowed to reach room temperature (20 °C to 25 °C) for up to 30 minutes before administration.

Do not use this medicine if the suspension contains large particles.

6. Contents of the container and other information

Composition of Azacitidine Sandoz

• The active substance is azacitidine. One vial contains 100 mg of azacitidine. After reconstitution with 4 ml of water for injections, the reconstituted suspension contains 25 mg/ml of azacitidine.
• The other component is mannitol (E421).

Appearance of the product and contents of the pack

Azacitidine Sandoz is a white powder for injectable suspension supplied in a glass vial with a rubber stopper and an aluminium seal with a plastic cap, containing 100 mg of azacitidine. The vial is stored in a cardboard box.

Pack size: 1 vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Pharmadox Healthcare Ltd,

KW20A Kordin Industrial Park

Paola, PLA3000

Malta

or

LEK farmacevtska družba d.d. (Lek Pharmaceuticals d.d.)

Verovškova ulica 57

1526 Ljubljana

Slovenia

or

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1

Barleben, Saxony-Anhalt, 39179

Germany

Date of the most recent review of this leaflet: January 2024.

Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Recommendations for safe handling

Azacitidine is a cytotoxic medicine and, as with other potentially toxic compounds, caution should be exercised when handling and preparing azacitidine suspensions. Procedures for the proper handling and disposal of anticancer medicines should be followed.

If reconstituted azacitidine comes into contact with the skin, the affected area should be washed immediately and thoroughly with soap and water. If contact occurs with mucous membranes, they should be thoroughly rinsed with water.

Incompatibilities

This medicine must not be mixed with other medicinal products except those mentioned below (see “Reconstitution procedure”).

Reconstitution procedure

Azacitidine Sandoz must be reconstituted with water for injections. The shelf life of the reconstituted medicine can be extended by reconstituting it with refrigerated water for injections (between 2 °C and 8 °C). Below is information on the storage of the reconstituted medicine.

1. The following items should be assembled:

Vial(s) of azacitidine; vial(s) of water for injections; non-sterile surgical gloves; alcohol-impregnated wipes; 5 ml syringe(s) with needle(s).

2. Withdraw 4 ml of water for injections into the syringe, ensuring that any trapped air is purged from the syringe.

3. Insert the needle of the syringe containing the 4 ml of water for injections through the rubber stopper of the azacitidine vial; then inject the water for injections into the vial.

4. After removing the syringe and needle, the vial should be shaken vigorously until a uniform, cloudy suspension is obtained. After reconstitution, each ml of suspension contains 25 mg of azacitidine (100 mg/4 ml). The reconstituted product is a cloudy, homogeneous suspension without clumps. The product must be discarded if large particles or clumps are present. Do not filter the suspension after reconstitution, as this may remove the active substance. Note that some adapters, infusion needles, and closed systems contain filters; therefore, such systems must not be used for administering the medicine after reconstitution.

5. Clean the rubber stopper and insert a new syringe with a needle into the vial. Invert the vial, ensuring that the tip of the needle is below the liquid level. Then pull back the plunger to withdraw the required amount of medicine for the correct dose, ensuring that any trapped air in the syringe is purged. Then remove the syringe with the needle from the vial and discard the needle.

6. Firmly attach a new subcutaneous needle (25 gauge is recommended) to the syringe. The needle should not be purged before injection to reduce the incidence of local reactions at the injection site.

7. When more than one vial is required, repeat all the above steps for preparing the suspension. For doses requiring more than one vial, the dose should be divided equally, for example, a 150 mg dose = 6 ml; two syringes with 3 ml in each syringe. Due to retention in the vial and needle, it may not be possible to withdraw all the suspension from the vial.

8. The contents of the dosing syringe must be resuspended immediately before administration. Allow the syringe containing the reconstituted suspension to reach room temperature (approximately between 20 °C and 25 °C) for up to 30 minutes before administration. If the elapsed time exceeds 30 minutes, the suspension must be properly discarded and a new dose prepared. To resuspend, roll the syringe vigorously between the palms of the hands until a uniform, cloudy suspension is obtained. The product must be discarded if large particles or clumps are present.

Storage of the reconstituted medicine

When azacitidine is reconstituted using non-refrigerated water for injections, chemical and physical in-use stability of the reconstituted medicine has been demonstrated at 25 °C for 60 minutes and between 2 °C and 8 °C for 24 hours when stored in the vial and in the syringe.

The shelf life of the reconstituted medicine can be extended by reconstituting with refrigerated water (between 2 °C and 8 °C) for injections. When azacitidine is reconstituted using refrigerated water (between 2 °C and 8 °C) for injections, chemical and physical in-use stability of the reconstituted medicine has been demonstrated between 2 °C and 8 °C for 36 hours when stored in the vial and for 30 hours between 2 °C and 8 °C when stored in the syringe.

From a microbiological standpoint, the reconstituted product should be used immediately. If not used immediately, the responsibility for the storage times and conditions prior to use lies with the user and must not exceed 24 hours between 2 °C and 8 °C.

Calculation of an individual dose

The total dose, based on body surface area (BSA), can be calculated as follows:

Total dose (mg) = dose (mg/m²) × BSA (m²)

The following table is provided only as an example of how to calculate individual azacitidine doses based on an average BSA value of 1.8 m².

Administration method

Do not filter the suspension after reconstitution.

Reconstituted Azacitidina Sandoz must be injected subcutaneously (insert the needle at an angle of 45 to 90°) using a 25-gauge needle into the upper arm, thigh, or abdomen.

Doses exceeding 4 ml must be administered at two separate injection sites.

Injection sites should be rotated. New injections should be administered at least 2.5 cm away from the previous injection site and never into sensitive, bruised, red, or hardened areas.

Any unused medicine and all materials that have come into contact with it should be disposed of according to local regulations.