AZACITIDINE 25 mg /Ml Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Azacitidine Glenmark, 25 mg/ml, powder for suspension for injection
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Azacitidine Glenmark and what is it used for
   1. What is Azacitidine Glenmark
   2. What is Azacitidine Glenmark used for
   3. How does Azacitidine Glenmark work
4. Important information before using Azacitidine Glenmark
   1. When not to use Azacitidine Glenmark
   2. Warnings and precautions
   3. Children and adolescents
   4. Azacitidine Glenmark and other medicines
   5. Pregnancy, breastfeeding, and fertility
   6. Driving and using machines
5. How to use Azacitidine Glenmark
6. Possible side effects
   1. Tell your doctor immediately if the patient notices any of the following side effects:
   2. Reporting side effects
7. How to store Azacitidine Glenmark
8. Contents of the packaging and other information
   1. What Azacitidine Glenmark contains
   2. What Azacitidine Glenmark looks like and contents of the pack
   3. Marketing authorization holder
   4. Manufacturer/Importer
   5. To obtain more detailed information, please contact the local representative of the marketing authorization holder:
   6. Information intended for healthcare professionals only:
   7. Doses above 4 ml should be injected at two different sites.

Leaflet accompanying the packaging: information for the user

Azacitidine Glenmark, 25 mg/ml, 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.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including those 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 Glenmark and what is it used for
• 2. Important information before using Azacitidine Glenmark
• 3. How to use Azacitidine Glenmark
• 4. Possible side effects
• 5. How to store Azacitidine Glenmark
• 6. Contents of the packaging and other information

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

What is Azacitidine Glenmark

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

What is Azacitidine Glenmark used for

Azacitidine Glenmark 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 the production of blood cells.

How does Azacitidine Glenmark work

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

2. Important information before using Azacitidine Glenmark

When not to use Azacitidine Glenmark

• if the patient is allergic to azacitidine or any of the other ingredients of this medicine (listed in section 6),
• if the patient has advanced liver cancer,
• if the patient is breastfeeding.

Warnings and precautions

Before starting treatment with Azacitidine Glenmark, discuss it with your doctor, pharmacist, or nurse:

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

Azacitidine Glenmark may cause a severe immune reaction called "differentiation syndrome" (see section 4).
Blood tests
Before starting treatment with Azacitidine Glenmark 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 the patient has a sufficient number of blood cells and if the liver and kidneys are working properly.

Children and adolescents

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

Azacitidine Glenmark and other medicines

Tell your doctor or pharmacist about all medicines the patient is taking or has recently taken, as well as any medicines the patient plans to take. This is because Azacitidine Glenmark may affect the way some other medicines work. Also, some other medicines may affect the way Azacitidine Glenmark works.

Pregnancy, breastfeeding, and fertility

Pregnancy
Azacitidine Glenmark should not be used during pregnancy, as it may harm the baby. Women who may become pregnant should use effective contraception while taking Azacitidine Glenmark and for 6 months after the end of treatment. If the patient becomes pregnant during treatment, they should inform their doctor immediately.
Breastfeeding
Azacitidine Glenmark should not be used during breastfeeding. It is not known if this medicine passes into human milk.
Fertility
Men should not father a child while receiving Azacitidine Glenmark. Men should use effective contraception while taking Azacitidine Glenmark and for 3 months after the end of treatment with this medicine. The patient should consult their doctor if they wish to store sperm before starting this treatment.

Driving and using machines

If side effects such as fatigue occur, the patient should not drive vehicles, use tools, or operate machines.

3. How to use Azacitidine Glenmark

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

• The recommended dose is 75 mg per square meter of body surface area. The doctor will determine the correct dose of this medicine for the patient, depending on the patient's overall condition, height, and weight. The doctor will check the progress of the treatment and, if necessary, may change the dose.
• Azacitidine Glenmark is given daily for one week, followed by a rest period of 3 weeks. This "treatment cycle" will be repeated every 4 weeks. The patient will usually receive at least 6 cycles of treatment.

Azacitidine Glenmark is given to the patient as a subcutaneous injection by a doctor or nurse. It can be given under the skin of the thigh, abdomen, or arm.
If the patient has any further doubts about the use of this medicine, they should consult their doctor, pharmacist, or nurse.

4. Possible side effects

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

Tell your doctor immediately if the patient notices any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and easy bruising.These may be symptoms of liver failure and can be life-threatening.
• Swelling of the feet and ankles, back pain, decreased urine output, increased thirst, rapid heartbeat, dizziness, and nausea, vomiting, or decreased appetite, as well as disorientation, restlessness, 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 brain. 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). The patient may feel tired and be pale.
• Decreased white blood cell count. This may be accompanied by fever. The patient is also more susceptible to infections.
• Low platelet count (thrombocytopenia). The patient is 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 disorders (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 in which the number of red and white blood cells and platelets is reduced.
• Urinary tract infection.
• Viral infection causing herpes.
• Gingival bleeding, gastrointestinal bleeding, rectal bleeding 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 on exertion.
• Throat and larynx pain.
• Nausea.
• Weakness.
• General malaise.
• Anxiety.
• Disorientation.
• Hair loss.
• Kidney failure.
• Dehydration.
• White coating 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, weakness.
• Bleeding at the injection site.
• Intestinal disease, which may cause fever, vomiting, and abdominal pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• Muscle spasms.
• Urticaria (hives), a raised, itchy rash on the skin.
• 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, 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 - metabolic complications that can occur during cancer treatment, and sometimes without treatment. These complications are caused by the breakdown products 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 dysfunction, heart rhythm disturbances, seizures, and sometimes death.

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

• Infection of the deep layers of the skin, which can spread quickly, causing skin and tissue damage, and can be life-threatening (necrotizing fasciitis).
• 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 the formation of a rash (cutaneous vasculitis).

Reporting side effects

If any side effects occur, including those not listed in this leaflet, the patient should inform their doctor or pharmacist. 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; phone: +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, more information can be collected on the safety of the medicine.

5. How to store Azacitidine Glenmark

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or label after "EXP". The expiry date refers to the last day of the month stated.
The doctor, pharmacist, or nurse is responsible for storing Azacitidine Glenmark. They are also responsible for preparing Azacitidine Glenmark and disposing of any unused remains properly.
Unopened vials - no special storage precautions.
For immediate use
After preparation, the suspension should be administered within 45 minutes.
For later use
If the Azacitidine Glenmark suspension was prepared using unrefrigerated 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 longer than 8 hours.
If the Azacitidine Glenmark suspension was prepared using refrigerated (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 longer than 32 hours.
The suspension should be left at room temperature (20–25 °C) for 30 minutes before administration. If more than 30 minutes have passed, the suspension should be discarded and a new dose prepared.

6. Contents of the packaging and other information

What Azacitidine Glenmark contains

The active substance is azacitidine.
One vial contains 100 mg of azacitidine. After preparation by adding 4 ml of water for injection, the prepared suspension contains 25 mg/ml of azacitidine.
The other ingredient is mannitol.

What Azacitidine Glenmark looks like and contents of the pack

Azacitidine is a white powder for suspension for injection and is supplied in a vial made of colorless glass type I with a butyl rubber stopper and an aluminum seal (white for 100 mg) in a cardboard box.
Available pack sizes:
1 vial containing 100 mg of azacitidine.

Marketing authorization holder

Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
140 78 Prague 4
Czech Republic

Manufacturer/Importer

AqVida GmbH
Kaiser-Wilhelm-Strasse 89
20355 Hamburg
Germany

To obtain more detailed information, please contact the local representative of the marketing authorization holder:

Glenmark Pharmaceuticals Sp. z o.o.
Osmańska 14
02-823 Warsaw
Date of last revision of the leaflet:January 2024
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Information intended for healthcare professionals only:

Recommendations for safe handling
Azacitidine Glenmark is a cytotoxic medicinal product, and as with other potentially toxic compounds, caution should be exercised when handling the azacitidine suspension. The procedures for the safe handling and disposal of anti-cancer medicinal products should be followed.
In case of contact with the prepared azacitidine, it should be washed immediately with soap and water. In case of contact with mucous membranes, they should be rinsed thoroughly with water.
Female healthcare professionals who are pregnant should not prepare the medicinal product.
Incompatibilities
Do not mix the medicinal product with other medicinal products, except for those listed below (see "Preparation procedure").
Preparation procedure
Azacitidine Glenmark should be prepared using water for injection. The shelf-life of the prepared medicinal product can be extended if refrigerated (2°C-8°C) water for injection is used. Details on the 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; syringe(s) for injection with needle(s).
• 2. Draw the appropriate amount of water for injection into the syringe (table below). Ensure that the air has been removed from the syringe.

• 3. Insert the needle of the syringe containing water for injection through the rubber stopper of the azacitidine vial and slowly inject the water for injection into the vial.
• 4. After removing the syringe and needle from the vial, shake the vial vigorously 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, needle hubs, and closed systems contain filters; therefore, such systems should not be used to administer the medicinal product after preparation.

Storage of the product after preparation
For immediate use
The Azacitidine Glenmark suspension can be prepared immediately before use, and the prepared suspension should be administered within 45 minutes. If more than 45 minutes have passed, the prepared suspension should be discarded and a new dose prepared.
For later use
If unrefrigerated water for injection was used to prepare the product, the suspension should be stored in the refrigerator (2°C−8°C) immediately after preparation and stored in the refrigerator for no longer than 8 hours. If more than 8 hours of refrigerated storage have passed, the suspension should be discarded and a new dose prepared.
If refrigerated (2°C-8°C) water for injection was used to prepare the product, the prepared suspension should be stored in the refrigerator (2°C−8°C) immediately after preparation and stored in the refrigerator for no longer than 32 hours. If more than 32 hours of refrigerated storage have passed, the suspension should be discarded and a new dose prepared.
The suspension should be left at room temperature (20–25 °C) for 30 minutes before administration. If more than 30 minutes have passed, the suspension should be discarded and a new dose prepared.
Calculation of the individual dose
The total dose can be calculated based on the body surface area (BSA) as follows:
Total dose (mg) = 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 Glenmark 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.

The injection sites should be changed. New injections should be given at least 2.5 cm from the previous site and never in irritated, bruised, red, or indurated areas.
Any unused medicinal product or waste materials should be disposed of in accordance with local regulations.