Prospecto: information for the user

Azacitidina Eugia 25 mg/ml powder for injectable suspension EFG

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-This medicine has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1.What is Azacitidina Eugia and how it is used

2.What you need to know before starting to use Azacitidina Eugia

3.How to use Azacitidina Eugia

4.Possible adverse effects

5.Storage of Azacitidina Eugia

6.Contents of the package and additional information

What is Azacitidina Eugia

Azacitidina is an anticancer agent that belongs to a group of medications called “antimetabolites”. Azacitidina Eugia contains the active ingredient “azacitidina”.

What is Azacitidina Eugia used for

Azacitidina 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 Eugia works

Azacitidina works by preventing the growth of cancer cells. Azacitidina 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 activate or deactivate genes by interfering with the production of new RNA and DNA. It is believed that these actions correct the problems of maturation and growth of healthy blood cells in the bone marrow that cause myelodysplastic disorders and kill cancer cells in leukemia.

Consult a doctor or nurse if you have any questions about how azacitidina works or why you have been prescribed this medication.

No useAzacitidina Eugia

•If you are allergic toazacitidinaor to any of the other components of this medication (listed in section 6).

•If you have advanced liver cancer.

•If you are breastfeeding.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use azacitidina:

•If you have a decrease in platelet, red blood cell, or white blood cell count.

•If you have a kidney disease.

•If you have a liver disease.

•If you have ever had a heart disease or a myocardial infarction, or have a history of lung disease.

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

Blood tests

Before starting treatment with azacitidina and at the beginning of each treatment period (called “cycle”) blood tests will be performed. This is done to check that you have a sufficient number of blood cells and that your liver and kidneys are functioning correctly.

Children and adolescents

Azacitidina is not recommended for use in children and adolescents under 18 years old.

Other medications andAzacitidina Eugia

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. This is because azacitidina may affect how other medications work. Similarly, other medications may affect how azacitidina works.

Pregnancy, breastfeeding, and fertility

Pregnancy

You should not use azacitidina during pregnancy because it may be harmful to the baby.

If you are a woman and may become pregnant, you should use an effective contraceptive method while using azacitidina and for 6 months after completing treatment with azacitidina. Inform your doctor immediately if you become pregnant during treatment.

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

Breastfeeding

Azacitidina should not be used during breastfeeding. It is unknown whether this medication passes into breast milk.

Fertility

Males should not conceive a child while receiving treatment with azacitidina. Men should use an effective contraceptive method while using azacitidina and for 3 months after completing treatment with azacitidina.

Consult your doctor if you wish to preserve your sperm before receiving this treatment.

Driving and operating machinery

Do not drive or use tools or machines if you experience adverse effects, such as fatigue.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Before administering azacitidina, your doctor will administer another medication to prevent nausea and vomiting at the beginning of each treatment cycle.

•The recommended dose is 75 mg/m2of body surface area. Your doctor will decide your dose of this medication based on your general condition, height, and weight. Your doctor will monitor your progress and, if necessary, change your dose.

•Azacitidina is administered every day for one week, followed by a three-week rest period. This “treatment cycle” will be repeated every four weeks. You will generally receive at least six treatment cycles.

A doctor or nurse will administer this medication as a subcutaneous injection under the skin. It can be administered under the skin of the thigh, abdomen, or arm (above the elbow).

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

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

Inform your doctor immediately if you observe any of the following side effects:

•Drowsiness, tremors, jaundice, abdominal bloating, and bruising. They may be symptoms of liver failure and can be potentially fatal.

•Swelling of the legs and feet, back pain, decreased urine output, increased thirst, rapid pulse, dizziness, and nausea, vomiting, or decreased appetite and a feeling of confusion, restlessness, or fatigue. They may be symptoms of kidney failure and can be potentially fatal.

•Fever. It could be due to an infection as a result of having low white blood cell counts, which can be potentially fatal.

•Chest pain or difficulty breathing that may be accompanied by fever. It may be due to a lung infection known as "pneumonia" and can be potentially fatal.

•Bleeding. For example, blood in the stool, due to bleeding in the stomach or intestines, or bleeding in the head. These may be symptoms of having low platelet counts in the blood.

•Difficulty breathing, swelling of the lips, itching, or skin rash. They 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. It may be accompanied by fever. You also have a higher probability of suffering from 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.

•Fatigue (fatigue).

•Reaction at the injection site, which includes redness, pain, or a skin rash.

•Loss of appetite.

•Joint pain.

•Bruising.

•Skin rash.

•Red or purple spots under the skin.

•Abdominal pain.

•Itching.

•Fever.

•Sore throat and runny nose.

•Dizziness.

•Headache.

•Difficulty falling asleep (insomnia).

•Nosebleed (epistaxis).

•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 head.

•Blood infection caused by bacteria (sepsis). It may be due to low white blood cell counts in the blood.

•Bone marrow failure. It may cause low red and white blood cell counts and platelet counts.

•A type of anemia in which there is a decrease in red and white blood cells and platelets.

•Urinary tract infection.

•A viral infection that causes herpes-like lesions.

•Bleeding gums, bleeding stomach or intestines, bleeding around the anus due to hemorrhoidal bleeding, bleeding in the eyes, bleeding under the skin or inside the skin (hematoma).

•Blood in the urine.

•Mouth or tongue ulcers.

•Changes in the skin at the injection site. These may be swelling, a hard lump, bruising, bleeding into the skin (hematoma), skin rash, itching, and changes in skin color.

•Redness of the skin.

•Skin infection (cellulitis).

•Throat and nasal infection, or sore throat.

•Runny nose or sinusitis.

•High or low blood pressure (hypertension or hypotension).

•Difficulty breathing when moving.

•Sore throat and larynx.

•Indigestion.

•Drowsiness (somnolence).

•Feeling unwell.

•Anxiety.

•Feeling confused.

•Loss of hair.

•Kidney failure.

•Dehydration.

•White coating on the tongue, inside the cheeks, and sometimes the palate, gums, and tonsils (oral fungal infection).

•Fainting.

•Decreased blood pressure when standing (orthostatic hypotension) that causes dizziness when standing or sitting.

•Sleep, drowsiness (somnolence).

•Bleeding due to a catheter.

•A disease that affects the intestine that can cause fever, vomiting, and stomach pain (diverticulitis).

•Fluid around the lungs (pleural effusion).

•Chills (rigors).

•Muscle spasms.

•Skin rash with itching (urticaria).

•Fluid accumulation around the heart (pericardial effusion).

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

•Dry cough.

•Swelling without pain of the fingertips (finger drumsticks).

•Tumor lysis syndrome – complications may occur during cancer treatment and sometimes even without treatment. These complications occur as a result of the product of dying tumor cells and may include: changes in blood biochemistry, high potassium, phosphorus, and uric acid levels, and low calcium levels that, therefore, generate changes in renal function and heart rhythm, convulsions, and sometimes death.

Unknown frequency(cannot be estimated from available data)

•Deep skin infection that spreads quickly damaging the skin and tissue, which can be potentially fatal (necrotizing fasciitis).

•Severe immune reaction (differentiation syndrome) that may cause fever, cough, difficulty breathing, skin rash, decreased urine output, low blood pressure (hypotension), swelling of the arms or legs, and rapid weight gain.

•Skin blood vessel inflammation that may cause skin rash (cutaneous vasculitis).

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medicationafter the expiration date that appears on the vial label and the box after CAD. The expiration date is the last day of the month indicated.

Your doctor, pharmacist, or nurse is responsible for the conservation of this medication. They are also responsible for the correct preparation and disposal of unused medication.

Unopened vials of this medication do not require special storage conditions.

If used immediately

The suspension should be administered within 45 minutes of preparation.

If used later

If azacitidine suspension is prepared using non-refrigerated injectable preparation water, the suspension should be placed in the refrigerator (between 2 °C and 8 °C) immediately after preparation and kept refrigerated for a maximum of 8 hours.

If azacitidine suspension is prepared using refrigerated injectable preparation water (between 2 °C and 8 °C), the suspension should be placed in the refrigerator (between 2 °C and 8 °C) immediately after preparation and kept refrigerated for a maximum of 22 hours.

The suspension should be allowed to reach an ambient temperature of 20 °C to 25 °C for a maximum of 30 minutes before administration.

From a microbiological point of view, the reconstituted medication should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user.

The suspension should be discarded if it contains large particles.

Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the containers and unused medications. This will help protect the environment.

Composition ofAzacitidine Eugia

-The active ingredient is azacitidine. A vial contains 100 mg of azacitidine. After reconstitution with 4 ml of water for injection, the reconstituted solution contains 25 mg/ml of azacitidine.

-The other component is mannitol.

Appearance of the productand contents of the package

Lyophilized powder or paste for injectable suspension, white or off-white in color.

Azacitidine Eugia is presented in a glass vial containing 100 mg of azacitidine. Each package contains 1 vial of azacitidine.

The vial may be packaged with or without a plastic protective wrapper.

Azacitidine 100 mg is supplied in packages of 1, 5, 7, and 10 vials.

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Responsible manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

Further information about this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Germany:Azacitidine PUREN 25 mg/ml Powder for the preparation of an injection suspension

Belgium:Azacitidine Eugia 25mg/ml powder for suspension for injection/poudre pour suspension injectable/Pulver zur Herstellung einer Injektionssuspension

Spain:Azacitidine Eugia 25 mg/ml powder for injectable suspension EFG

France:AZACITIDINE ARROW 25 mg/ml, powder for injection suspension

Italy:Azacitidine Aurobindo

Netherlands:Azacitidine Eugia25 mg/ml powder for suspension for injection

Poland:AzacitidineEugia

Portugal:Azacitidine Eugia

Romania:Azacitidine Eugia 25 mg/ml powder for injectable suspension

Last review date of this leaflet: December 2023

The detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals

Recommendations for safe handling

Azacitidine is a cytotoxic drug and, like other potentially toxic compounds, caution should be exercised when handling and preparing azacitidine suspensions. The procedures for correct handling and disposal of cancer medications should be applied.

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

Incompatibilities

This medicinal product should not be mixed with others, except as mentioned below (see "Reconstitution procedure").

Reconstitution procedure

Azacitidine Eugia should be reconstituted with water for injection. The shelf life of the reconstituted medicinal product can be extended by reconstituting it with refrigerated water for injection (between 2 °C and 8 °C). The following information is provided on the storage of the reconstituted medicinal product.

1.The following items should be mounted:

Vial(s) of azacitidine; vial(s) of water for injection; non-sterile surgical gloves; alcohol-moistened wipes; 5 ml injection syringes with needles.

2.4 ml of water for injection should be extracted from the syringe, ensuring that the air trapped inside the syringe is purged.

3.The needle of the syringe containing the 4 ml of water for injection should be inserted through the rubber stopper of the vial of azacitidine; then, the water for injection should be injected into the vial.

4.After extracting the syringe and needle, the vial should be shaken vigorously until a uniform turbid suspension is obtained. After reconstitution, each ml of suspension will contain 25 mg of azacitidine (100 mg/4 ml). The reconstituted product is a uniform and turbid suspension, without aggregates. The suspension should be discarded if it contains large particles or aggregates. Do not filter the suspension after reconstitution, as this may eliminate the active ingredient. Note that some adapters, perfusion needles, and closed systems contain filters; therefore, these systems should not be used for administering the medicinal product after reconstitution.

5.The rubber stopper should be cleaned and a new syringe with a needle should be introduced into the vial. Then, the vial should be inverted, ensuring that the tip of the needle is below the liquid level. Next, the plunger should be pulled back to extract the amount of medicinal product necessary for the correct dose, ensuring that the air trapped inside the syringe is purged. Then, the syringe with the needle should be extracted from the vial, and the needle should be discarded.

6.Next, a new subcutaneous needle (it is recommended to use a caliber 25) should be tightly attached to the syringe. The needle should not be purged before injection, in order to reduce the incidence of local reactions at the injection site.

7.If more than 1 vial is needed, all the above steps should be repeated for the preparation of the suspension. In the case of doses that require more than 1 vial, the dose should be divided into equal parts, for example, a dose of 150 mg = 6 ml; 2 syringes with 3 ml in each syringe. Due to retention in the vial and needle, it may not be possible to extract all the suspension from the vial.

8.The content of the dosing syringe should be resuspended immediately before administration. The temperature of the suspension at the time of injection should be approximately 20 °C to 25 °C. To resuspend, vigorously roll the syringe between the palms of the hands until a uniform and turbid suspension is obtained. The suspension should be discarded if it contains large particles or aggregates.

Storage of the reconstituted medicinal product

For immediate use

The azacitidine suspension can be prepared immediately before use, and the reconstituted suspension should be administered within 45 minutes. If the time elapsed is greater than 45 minutes, the reconstituted suspension should be discarded correctly and a new dose should be prepared.

For later use

When reconstituted with non-refrigerated water for injection, the reconstituted suspension should be refrigerated (between 2 °C and 8 °C) immediately after reconstitution and stored refrigerated for a maximum of 8 hours. If the time elapsed in the refrigerator is greater than 8 hours, the suspension should be discarded correctly and a new dose should be prepared.

When reconstituted with refrigerated water for injection (between 2 °C and 8 °C), the reconstituted suspension should be refrigerated (between 2 °C and 8 °C) immediately after reconstitution and stored refrigerated for a maximum of 22 hours. If the time elapsed in the refrigerator is greater than 22 hours, the suspension should be discarded correctly and a new dose should be prepared.

The loaded syringe should be allowed to reach a temperature of approximately 20 °C to 25 °C for a maximum of 30 minutes before administration. If the time elapsed is greater than 30 minutes, the suspension should be discarded correctly and a new dose should be prepared.

Calculation of an individual dose

The total dose, according to body surface area (SC), can be calculated as follows:

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

The following table is presented only as an example to calculate individual doses of azacitidine, based on an average SC value of 1.8 m2.

Administration form

Do not filter the suspension after reconstitution.

Azacitidine reconstituted should be injected subcutaneously (insert the needle at an angle of 45 to 90°), with a caliber 25 needle, in the arm, thigh, or abdomen.

Doses greater than 4 ml should be injected in two separate locations.

The injection sites should be rotated. New injections should be administered at least 2.5 cm away from the previous site and never in sensitive areas, with ecchymosis, redness, or hardening.

The elimination of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations.