Gerodaza

Package leaflet: Information for the patient

Gerodaza, 25 mg/ml, powder for suspension for injection
Azacitidinum
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, please consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Gerodaza is and what it is used for

What Gerodaza is
Gerodaza is an anticancer medicine belonging to a group of drugs known as "antimetabolites". Gerodaza contains the active substance called "azacitidine".

What Gerodaza is used for
Gerodaza is used in adults who are not eligible for hematopoietic stem cell transplantation, for the treatment of:

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

These diseases affect the bone marrow and may impair the normal production of blood cells.

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 mechanism of action involves altering the activation and deactivation of cellular genes, as well as interfering with the synthesis of RNA and DNA. These actions are thought to correct the impaired maturation and growth of young blood cells in the bone marrow that lead to myelodysplastic disorders, and to kill cancer cells in leukemia.

If you have any questions about how Gerodaza works or why this medicine has been prescribed, please consult your doctor or nurse.

2. Important information before using Gerodaza

When not to use Gerodaza

• if the patient is allergic (hypersensitive) to azacitidine or to 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 Gerodaza, discuss with your doctor, pharmacist or nurse if the patient:

• has low platelet counts, red blood cells or white blood cells,
• has kidney disease,
• has liver disease,
• has previously had heart disease, myocardial infarction (heart attack) or any lung disease.

Gerodaza may cause a serious immune reaction called "differentiation syndrome" (see section 4).
Blood tests
Blood tests will be performed before starting treatment with Gerodaza and at the beginning of each treatment period (so-called "cycle"). The purpose of these tests is to check whether the patient has sufficient blood cell counts and whether the liver and kidneys are functioning properly.

Children and adolescents
Gerodaza is not recommended for use in children and adolescents under 18 years of age.

Gerodaza and other medicines
Tell your doctor, pharmacist or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Gerodaza may affect the way some medicines work. Likewise, some other medicines may affect the way Gerodaza works.

Pregnancy, breastfeeding and fertility

Pregnancy
Do not use Gerodaza during pregnancy, as it may be harmful to the unborn child. Women who could become pregnant should use an effective method of contraception during treatment with Gerodaza and for 6 months after stopping treatment with this medicine. Inform your doctor immediately if pregnancy occurs during treatment with Gerodaza.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Breastfeeding
Do not breastfeed while taking Gerodaza. It is not known whether this medicine passes into human milk.

Fertility
Men should not father a child during treatment with Gerodaza. An effective method of contraception should be used during and for 3 months after the treatment period.
Patients should consult their doctor if they wish to preserve sperm before starting this treatment.

Driving and using machines
If side effects such as fatigue occur, do not drive, operate tools or handle machinery.

3. How to take Gerodaza

Before administering Gerodaza to the patient, the doctor will give an additional medicine to prevent nausea and vomiting at the beginning of each treatment cycle.

• The recommended dose is 75 mg per m² of body surface area. The doctor selects the appropriate dose of Gerodaza for the patient depending on the patient's general condition, height and body weight. The doctor monitors progress during treatment and may adjust the dose if necessary.
• Gerodaza is administered daily for one week, followed by a rest period lasting 3 weeks. This "treatment cycle" is repeated every 4 weeks. The patient usually receives at least 6 treatment cycles.

Gerodaza is given as a subcutaneous injection by a doctor or nurse. It may be administered subcutaneously in the thigh, abdomen, or arm.
If you have any further questions regarding the use of this medicine, please consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everyone gets them.
You should immediately tell your doctor 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 may be life-threatening.
• Swelling of the legs and feet, back pain, reduced urine output, increased thirst, rapid heartbeat, dizziness and nausea, vomiting or loss of appetite, and a feeling of disorientation, anxiety or fatigue. These may be symptoms of kidney failure, which may be life-threatening.
• Fever. This may be due to an infection caused by a low number of white blood cells, which may be life-threatening.
• Chest pain or shortness of breath, possibly accompanied by fever. This may be due to a lung infection called "pneumonia," which may be life-threatening.
• Bleeding. Such as blood in the stool due to bleeding in the stomach or intestine, or bleeding inside the head. 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 number of red blood cells (anaemia). The patient may feel tired and look pale.
• Decreased number of white blood cells. This may be accompanied by fever. The patient also has an increased susceptibility to infections.
• Low platelet count (thrombocytopenia). The patient has an increased risk of bleeding and bruising.
• Constipation, diarrhoea, 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.
• Pain in the nose and throat.
• Dizziness.
• Headache.
• Sleep problems (insomnia).
• Nosebleeds.
• Muscle pain.
• Weakness.
• Weight loss.
• Low blood potassium levels.

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

• Bleeding inside the skull.
• Blood infection caused by bacteria (sepsis). This may be due to a low number of white blood cells in the blood.
• Bone marrow failure. This may lead to low numbers of red and white blood cells and platelets.
• A type of anaemia in which the number of red and white blood cells and platelets is reduced.
• Urinary tract infection.
• Viral infection causing cold sores on the lips.
• Bleeding gums, bleeding in the stomach or intestine, bleeding from the anal area due to haemorrhoids (haemorrhoidal bleeding), eye bleeding, bleeding under or into the skin (haematomas).
• Blood in the urine.
• Ulceration of the mouth or tongue.
• Skin changes at the injection site. These include swelling, hard lumps, bruising, bleeding into the skin (haematomas), rash, itching and skin colour changes.
• Redness of the skin.
• Skin infection (cellulitis).
• Infection of the nose and throat or sore throat.
• Pain in the nose or nasal congestion, or sinus pain (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath during physical activity.
• Pain in the throat and larynx.
• Indigestion.
• Lethargy.
• General malaise.
• Anxiety.
• Disorientation.
• Excessive 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 upon standing (orthostatic hypotension), leading to dizziness when changing to a standing or sitting position.
• Drowsiness.
• Bleeding at the catheter insertion site.
• Disease affecting the intestine, which may present with fever, vomiting and abdominal pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• Muscle cramps.
• Raised, itchy rash on the skin (urticaria).
• 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-coloured, raised, painful skin patches, with fever.
• Painful skin ulceration (pyogenic necrotising skin inflammation).
• 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).
• Tumour lysis syndrome – metabolic complications that may occur during cancer treatment, and sometimes even without treatment. These complications are caused by the products of dying tumour cells and may include: changes in blood chemistry; high levels of potassium, phosphate, and uric acid, and low calcium levels, leading to kidney dysfunction, heart rhythm disturbances, seizures, and sometimes death.

Frequency unknown (frequency cannot be estimated from available data)

• Infection of deep skin layers that spreads rapidly, causing skin and tissue damage, which may be life-threatening (necrotising fasciitis).
• Severe immune reaction (differentiation syndrome), which may cause fever, cough, difficulty breathing, rash, reduced urine output, low blood pressure (hypotension), swelling of the face or legs, and sudden weight gain.
• Inflammation of blood vessels in the skin, which may result in a rash (cutaneous vasculitis).

Reporting of side effects
If you experience any adverse symptoms, including any not listed in this leaflet, you should inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 authorisation holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gerodaza

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 vial label after EXP. The expiry date refers to the last day of the specified month.
The doctor, pharmacist, or nurse is responsible for storing Gerodaza, preparing the medicine, and properly disposing of any unused portions.

Unopened vials – no special storage instructions required.

After preparation:
For azacitidine solution prepared with unrefrigerated water for injections, chemical and physical in-use 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 in-use period of the prepared medicinal product may be extended by dissolving the product using refrigerated (2°C to 8°C) water for injections. For azacitidine solution prepared with refrigerated (2°C to 8°C) water for injections, chemical and physical in-use stability of the prepared medicinal product has been demonstrated for 32 hours at 2°C to 8°C.

From a microbiological standpoint, the prepared product should be used immediately. If not used immediately, the user is responsible for ensuring the duration and conditions of storage prior to use, which must not exceed 8 hours at 2°C to 8°C for product prepared with unrefrigerated water for injections, or 32 hours for product prepared with refrigerated (2°C to 8°C) water for injections.

Allow the suspension to reach room temperature (20°C to 25°C) for up to a maximum of 30 minutes before administration.

If large particles are present in the suspension, discard it.

6. Contents of the package and other information

What Gerodaza contains

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

What Gerodaza looks like and contents of the pack
Gerodaza is a white lyophilized powder for the preparation of a suspension for injection, packed in
vials made of colourless type I glass, closed with a bromobutyl rubber stopper coated with ETFE
(the top of the stopper additionally coated with polymerized silicone RB2-40) and an aluminium seal
(white for 100 mg and orange for 150 mg).
Pack sizes:
1 vial containing 100 mg of azacitidine.
1 vial containing 150 mg of azacitidine.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria

Manufacturer
AqVida GmbH
Kaiser-Wilhelm-Str. 89
20355 Hamburg
Germany

For further information, contact the representative of the Marketing Authorisation Holder:
G.L. PHARMA POLAND Sp. z o.o.
Al. Jana Pawła II 61/313
01-031 Warsaw, Poland
Tel: 022/ 636 52 23; 636 53 02
[email protected]

Information intended exclusively for medical professionals:

Safety handling recommendations
Gerodaza is a cytotoxic medicinal product and, as with other potentially toxic compounds, caution must be exercised when preparing and handling the azacitidine suspension. Appropriate handling and disposal procedures for antineoplastic medicinal products should be followed.
In case of contact of prepared azacitidine with the skin, the skin should be immediately and thoroughly washed with soap and water. In case of contact with mucous membranes, they should be thoroughly rinsed with water.
Pregnant female medical personnel should not prepare this medicinal product.
Incompatibilities
Do not mix the medicinal product with other medicinal products except those mentioned below (see "Preparation procedure").
Preparation procedure
Azacitidine should be reconstituted with water for injections. The stability period of the prepared medicinal product may be extended by reconstituting the product using cooled (2°C to 8°C) water for injections. Details regarding storage of the prepared product are provided below.

1. Gather the following items: vial(s) of azacitidine, vial(s) of water for injections, non-sterile surgical gloves, alcohol swabs, syringe(s) and needle(s) for injection.
2. Draw the appropriate volume of water for injections into the syringe (see table below). Ensure that all air has been expelled from the syringe.

3. Insert the needle of the syringe containing water for injections through the rubber stopper of the vial with azacitidine and then slowly 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. The prepared product is a uniform, cloudy suspension free of aggregates. The suspension should be discarded if it contains large particles or aggregates. The suspension must not be filtered after reconstitution, as this may lead to removal of the active substance. It should be noted that certain adapters, spikes, and closed systems contain filters. Therefore, such components should not be used for administering the medicinal product after reconstitution.

5. Clean the rubber stopper and insert a new needle with a syringe into the vial. Then invert the vial, ensuring that the tip of the needle is below the liquid level. Pull back the plunger to withdraw the required amount of medicinal product needed to administer the correct dose. Ensure that all air has been expelled from the syringe. Then remove the needle and syringe from the vial and discard the needle.

6. Firmly attach a new subcutaneous injection needle (recommended 25 G) to the syringe. Do not flush the needle prior to injection to reduce the frequency of local reactions at the injection site.

7. If more than one vial is required, repeat all the above steps to prepare the suspension. Due to adsorption onto the vial walls and needle, it may not be possible to withdraw the entire suspension from the vial.

8. The suspension in the syringe must be resuspended immediately before administration. For up to 30 minutes before administration, allow the syringe filled with the prepared suspension to reach a temperature of approximately 20°C to 25°C. If more than 30 minutes have elapsed, the suspension must be properly discarded and a new dose prepared. To re-obtain the suspension, vigorously roll the syringe between the palms until a uniform, cloudy suspension is achieved. The suspension should be discarded if it contains large particles or aggregates.

After preparation:
For azacitidine solution prepared with unrefrigerated water for injections, chemical and physical in-use 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 may be extended by reconstituting the product using refrigerated (2°C to 8°C) water for injections. For azacitidine solution prepared with refrigerated (2°C to 8°C) water for injections, chemical and physical in-use stability of the prepared medicinal product has been demonstrated for 32 hours at 2°C to 8°C.
From a microbiological point of view, the medicinal product should be used immediately after preparation. If not used immediately, the user is responsible for the duration of use and storage conditions prior to use, which must not exceed 8 hours at 2°C to 8°C for product prepared with unrefrigerated water for injections or 32 hours for product prepared with refrigerated (2°C to 8°C) water for injections.
For up to 30 minutes before administration, allow the syringe filled with the prepared suspension to reach a temperature of approximately 20°C to 25°C. If more than 30 minutes have elapsed, the suspension must be properly discarded and a new dose prepared.

Calculation of individual dose
The total dose can be calculated based on body surface area (BSA) as follows:
total dose (mg) = dose (mg/m²) × BSA (m²)
The table below is merely an example of how to calculate individual azacitidine doses based on an average BSA of 1.8 m².

Method of administration
Do not filter the suspension after preparation.
The prepared solution of Gerodaza should be injected subcutaneously (inserting the needle at an angle of 45° to 90°) using a 25 G needle into the arm, thigh, or abdomen.
Doses exceeding 4 ml should be administered at two different sites.
The injection site should be rotated. New injections should be administered at least 2.5 cm away from the previous injection site, and injections should never be given into irritated, bruised, red, or hardened areas.
Any unused portions of the medicinal product or waste materials should be disposed of in accordance with local regulations.