Gerodaza

Leaflet included in the packaging: patient information

Gerodaza, 25 mg/ml, powder for suspension for injection

Azacitidine
You should carefully read the contents of this leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should ask your doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Gerodaza and what is it used for

What is Gerodaza

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

What is Gerodaza used for

Gerodaza 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 Gerodaza works

Gerodaza 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 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 repair the disturbances in the maturation and growth 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 Gerodaza works or why it has been prescribed, you should ask your doctor or nurse.

2. Important information before using Gerodaza

When not to use Gerodaza

Warnings and precautions

Before starting treatment with Gerodaza, you should discuss with your doctor, pharmacist, or nurse if you:

• have a low platelet count, red blood cells, or white blood cells,
• have kidney disease,
• have liver disease,
• have had heart disease, heart attack, or any lung disease in the past.

Gerodaza may cause a severe immune reaction called "tumor lysis syndrome" (see section 4).
Blood tests
Before starting treatment with Gerodaza 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

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

Gerodaza and other medicines

You should tell your doctor, pharmacist, or nurse about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Gerodaza may affect the way some medicines work. Similarly, some other medicines may affect the way Gerodaza works.

Pregnancy, breastfeeding, and fertility

Pregnancy
You should not use Gerodaza during pregnancy, as it may harm the baby.
Women who may become pregnant should use effective contraception during treatment with Gerodaza and for 6 months after stopping treatment with this medicine.
You should tell your doctor immediately if you become pregnant during treatment with Gerodaza.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, you should ask your doctor or pharmacist for advice before using this medicine.

Breastfeeding
You should not breastfeed while using Gerodaza.
It is not known whether this medicine passes into human milk.

Fertility
Men should not father a child during treatment with Gerodaza.
You should use effective contraception during and for 3 months after treatment with this medicine.
You should 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, you should not drive, use tools, or operate machinery.

3. How to take Gerodaza

Before administering Gerodaza 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 Gerodaza for you, depending on your overall condition, height, and weight.
  The doctor will check the progress of your treatment and may change the dose if necessary.
• Gerodaza is given daily for one week, followed by a rest period of 3 weeks.
  This "treatment cycle" is repeated every 4 weeks.
  You will usually receive at least 6 cycles of treatment.

Gerodaza is given as an injection under the skin by a doctor or nurse.
It can be given under the skin in the thigh, abdomen, or arm.

If you have any further questions about using this medicine, you should ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

You should tell your doctor immediately if you notice any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal bloating, and easy bruising.
  These may be symptoms of liver failure, which can be life-threatening.
• Swelling of the feet and ankles, back pain, decreased urine output, increased thirst, rapid heartbeat, dizziness, nausea, vomiting, or loss of appetite, and a feeling of disorientation, anxiety, or fatigue.
  These may be symptoms of kidney failure, which can be life-threatening.
• Fever.
  This may be due to an infection caused by a low white blood cell count, which can be life-threatening.
• Chest pain or shortness of breath, which may be accompanied by fever.
  This may be due to 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.
  This may be due to 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 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.
• Purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Sleep disturbances (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 brain.
• Blood infection caused by bacteria (sepsis).
  This may be due to 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 reduced.
• Urinary tract infection.
• Viral infection causing cold sores.
• 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 throat.
• 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 throat pain.
• Nose and sinus pain (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath on exertion.
• Throat and larynx pain.
• Nausea.
• Indigestion.
• General feeling of being unwell.
• Fear.
• Disorientation.
• Excessive 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 accumulation around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Large, purple, raised, painful patches 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 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 function disorders, 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, which can be life-threatening (necrotizing fasciitis).
• Severe immune reaction (tumor lysis syndrome), which can cause fever, cough, difficulty breathing, rash, decreased urine output, low blood pressure (hypotension), swelling of the face or arms and legs, and sudden weight gain.
• Inflammation of the blood vessels in the skin, which can cause a rash (vasculitis).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 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, you can help provide more information on the safety of this medicine.

5. How to store Gerodaza

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label after EXP.
The expiry date refers to the last day of the month stated.

The doctor, pharmacist, or nurse is responsible for storing Gerodaza.
They are also responsible for preparing Gerodaza and disposing of any unused remains properly.

Unopened vials of the medicine - no special storage instructions.

After preparation:

For the azacitidine solution prepared in uncooled water for injection, chemical and physical stability of the prepared medicinal product has been demonstrated for 45 minutes at 25°C and for 8 hours at 2°C to 8°C.

The shelf life of the prepared medicinal product can be extended by dissolving the product using cooled (2°C to 8°C) water for injection.
For the azacitidine solution prepared in cooled (2°C to 8°C) water for injection, chemical and physical stability of the prepared medicinal product has been demonstrated for 32 hours at 2°C to 8°C.

For microbiological reasons, the prepared product should be used immediately.
If the product is not used immediately, the user is responsible for the storage time and conditions before use, which should not exceed 8 hours at 2°C to 8°C for the product prepared in uncooled water for injection or 32 hours for the product prepared in cooled (2°C to 8°C) water for injection.

The suspension should be allowed to reach room temperature (20°C to 25°C) for a maximum of 30 minutes before administration.
If more than 30 minutes have passed, the suspension should be discarded and a new dose prepared.

If there are large particles in the suspension, it should be discarded.

6. Contents of the packaging and other information

What Gerodaza contains

• The active substance is azacitidine.
  One milliliter of the prepared suspension contains 25 mg of azacitidine.
  One vial contains 100 mg or 150 mg of azacitidine.
• The other ingredient is mannitol.

What Gerodaza looks like and contents of the pack

Gerodaza is a white lyophilized powder for suspension for injection, packaged in vials made of colorless glass type I, closed with a bromobutyl rubber stopper coated with ETFE (the top of the stopper is additionally coated with polymerized silicone RB2-40) and an aluminum seal (white for 100 mg and orange for 150 mg).

Pack size:

1 vial containing 100 mg of azacitidine.

1 vial containing 150 mg of azacitidine.

Not all pack sizes may be marketed.

Marketing authorization holder

G.L. Pharma GmbH

Schlossplatz 1

8502 Lannach

Austria

Manufacturer

AqVida GmbH

Kaiser-Wilhelm-Str. 89

20355 Hamburg

Germany

To obtain more detailed information, you should contact the representative of the marketing authorization holder:

G.L. PHARMA POLAND Sp. z o.o.

Jana Pawła II Avenue 61/313

01-031 Warsaw, Poland

Phone: 022/ 636 52 23; 636 53 02

biuro@gl-pharma.pl

Date of last revision of the leaflet: 12.02.2024

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Information intended exclusively for healthcare professionals:

Recommendations for safe handling

Gerodaza is a cytotoxic medicinal product, and, as with other potentially toxic compounds, caution should be exercised when handling and preparing the azacitidine suspension.
Proper procedures for handling and disposal of anticancer medicinal products should be followed.

In case of skin contact with the prepared azacitidine, the skin should be washed immediately with soap and water.
In case of contact with mucous membranes, they should be flushed with water.

Pregnant women in the healthcare staff should not prepare this medicinal product.

Incompatibilities

The medicinal product should not be mixed with other medicinal products, except for those mentioned below (see "Preparation procedure")

Preparation procedure

Azacitidine should be reconstituted in water for injection.
The shelf life of the prepared medicinal product can be extended by reconstituting the product using cooled (2°C to 8°C) water for injection.

Details on storage of the prepared product are given below.

• 1. You should have the following products: vial(s) of azacitidine, vial(s) of water for injection, non-sterile surgical gloves, alcohol swabs, injection syringe(s) with needle(s).
• 2. You should draw up the appropriate amount of water for injection into the syringe (see the table below).
  Make sure that the air has been removed from the syringe.

• 3. You should insert the needle of the syringe containing 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, you should vigorously shake the vial until a uniform, cloudy suspension is obtained.
  After preparation, each milliliter of the suspension contains 25 mg of azacitidine.
  The prepared product is a uniform, cloudy suspension without agglomerates.
  You should 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.
  Such devices should not be used to administer the medicinal product after preparation.

After preparation:

For the azacitidine solution prepared in uncooled water for injection, chemical and physical stability of the prepared medicinal product has been demonstrated for 45 minutes at 25°C and for 8 hours at 2°C to 8°C.

The shelf life of the prepared medicinal product can be extended by dissolving the product using cooled (2°C to 8°C) water for injection.
For the azacitidine solution prepared in cooled (2°C to 8°C) water for injection, chemical and physical stability of the prepared medicinal product has been demonstrated for 32 hours at 2°C to 8°C.

For microbiological reasons, the prepared product should be used immediately.
If the product is not used immediately, the user is responsible for the storage time and conditions before use, which should not exceed 8 hours at 2°C to 8°C for the product prepared in uncooled water for injection or 32 hours for the product prepared in cooled (2°C to 8°C) water for injection.

You should allow the syringe filled with the prepared suspension to reach room temperature (20°C to 25°C) for a maximum of 30 minutes before administration.
If more than 30 minutes have passed, the suspension should be discarded and a new dose prepared.

To resuspend, you should vigorously shake the syringe between your hands until a uniform, cloudy suspension is obtained.
You should discard the suspension if it contains large particles or agglomerates.

• 5. You should clean the rubber stopper and insert a new needle with syringe into the vial.
  Then, you should turn the vial upside down, making sure that the needle tip is below the level of the liquid.
  Next, you should draw up the required amount of medicinal product.
  Make sure that the air has been removed from the syringe.
  Then, you should withdraw the needle and syringe from the vial and discard the needle.
• 6. You should attach a new injection needle (recommended 25 G) firmly to the syringe.
  Do not flush the needle before injection to minimize the risk of local reactions at the injection site.
• 7. If more than one vial is needed, you should repeat all the above steps to prepare the suspension.
  Due to settling of the product on the vial walls and in the needle, it may not be possible to withdraw the entire suspension from the vial.
• 8. The contents of the syringe with the dose should be resuspended immediately before administration.
  For a maximum of 30 minutes before administration, you should allow the syringe filled with the prepared suspension to reach room temperature (20°C to 25°C).
  If more than 30 minutes have passed, the suspension should be discarded and a new dose prepared.

Calculation of individual dose

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

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.

Administration

Do not filter the suspension after preparation.

The prepared Gerodaza solution should be injected subcutaneously (insert the needle at an angle of 45° to 90°) using a 25 G needle in the arm, thigh, or abdomen.

Doses greater than 4 ml should be injected at two different sites.

You should change the injection site.
New injections should be given at least 2.5 cm away from the previous site and never in areas that are tender, bruised, red, or hardened.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.