Azacitidine Eugia 25 mg/ml powder for injectable suspension EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Azacitidine Eugia 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. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Azacitidine Eugia is and what it is used for
2. What you need to know before using Azacitidine Eugia
3. How to use Azacitidine Eugia
4. Possible side effects
5. How to store Azacitidine Eugia
6. Contents of the pack and other information

1. What Azacitidina Eugia is and what it is used for

What Azacitidina Eugia is

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

What Azacitidina Eugia is used for

Azacitidine is used in adults who cannot receive a stem cell transplant to treat:

• High-risk myelodysplastic syndromes (MDS).
• Chronic myelomonocytic leukaemia (CMML).
• Acute myeloid leukaemia (AML).

These diseases affect the bone marrow and can cause problems in the normal production of blood cells.

How Azacitidina Eugia 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 switch genes on or off, through interference with the production of new RNA and DNA. These actions are thought to correct the abnormalities in maturation and growth of healthy blood cells in the bone marrow caused by myelodysplastic disorders, and to kill cancer cells in leukaemia.

Please 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 Eugia

Do not use Azacitidina Eugia

• 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.
• If you are breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using 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 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 Eugia

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 who can become pregnant, you must use an effective method of contraception while taking 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

Azacitidine must not be used during breastfeeding. It is unknown whether this medicine passes into breast milk.

Fertility

Men must not father a child while receiving treatment with azacitidine. Men should use an effective method of contraception while taking azacitidine and for 3 months after stopping treatment with azacitidine.

Consult 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 Eugia

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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 of body surface area. Your doctor will decide your dose of this medicine depending on your general condition, height, and weight. Your doctor will monitor your progress and, if necessary, may change your dose.
• Azacitidine is administered daily for one week, followed by a rest period of three weeks. 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 arm (above the elbow).

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.

Tell your doctor immediately 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, nausea, vomiting, loss of appetite, and feeling confused, restless, or fatigued. 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, possibly accompanied by fever. This may be due to a lung infection known as "pneumonia" and can be potentially fatal.
• Bleeding. For example, blood in the stools due to bleeding in the stomach or intestines, or internal bleeding in 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 get 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.
• Pain in the nose and throat.
• Dizziness.
• Headache.
• Trouble sleeping (insomnia).
• Nosebleeds (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low blood potassium levels.

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 intestine; bleeding around the anus due to hemorrhoidal bleeding; bleeding in the eyes; or bleeding under or into the skin (bruising or hematoma).
• Blood in the urine.
• Ulcers in the mouth or tongue.
• Skin changes at the injection site, such as swelling, a hard lump, bruising, bleeding into the skin (hematoma), rash, itching, or changes in skin color.
• Redness of the skin.
• Skin infection (cellulitis).
• Infection of the nose and throat, 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.
• Pain in the throat and larynx.
• Indigestion.
• Drowsiness (lethargy).
• Feeling unwell.
• Anxiety.
• Feeling confused.
• 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).
• Shivering (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, phosphate, and 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)

• Deep skin infection that spreads rapidly, 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 that may cause a 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: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Azacitidine Eugia

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

Do not use this medicine after the expiry date stated on the label of the vial and carton after EXP. The expiry date refers to the last day of the month indicated.

Your doctor, pharmacist, or nurse are responsible for the storage of this medicine. They are also responsible for the correct preparation and disposal of any unused medicine.

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

If used immediately

The suspension should be administered within 45 minutes of preparation.

If used later

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

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

The suspension should be allowed to reach room temperature (20 °C to 25 °C) for a maximum of 30 minutes prior to administration.

From a microbiological standpoint, the reconstituted medicine should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user.

The suspension should be discarded if it contains large particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Azacitidine Eugia

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

Appearance of the product and package contents

White or almost white lyophilized powder or paste for injectable suspension.

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

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

Azacitidine 100 mg is available in pack sizes of 1, 5, 7, and 10 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront
Floriana, FRN 1914
Malta

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

For further information about this medicine, contact the local representative of the Marketing Authorization Holder:

Aurovitas Spain, S.A.U.
Avda. de Burgos, 16-D
28036 Madrid
Spain

This medicine is authorized in the European Economic Area member states under the following names:

Germany: Azacitidin PUREN 25 mg/ml Pulver zur Herstellung einer Injektionssuspension
Belgium: Azacitidine Eugia 25mg/ml poeder voor suspensie voor injectie/poudre pour suspension injectable/Pulver zur Herstellung einer Injektionssuspension
Spain: Azacitidina Eugia 25 mg/ml polvo para suspensión inyectable EFG
France: AZACITIDINE ARROW 25 mg/ml, poudre pour suspension injectable
Italy: Azacitidina Aurobindo
Netherlands: Azacitidine Eugia 25 mg/ml poeder voor suspensie voor injectie
Poland: Azacitidine Eugia
Portugal: Azacitidina Eugia
Romania: Azacitidina Eugia 25 mg/ml pulbere pentru suspensie injectabila

Date of the most recent review of this leaflet: December 2023

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

Safe handling recommendations

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

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

Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned below (see "Reconstitution procedure").

Reconstitution procedure

Azacitidine Eugia must be reconstituted with water for injections. The stability of the reconstituted medicine can be extended by using refrigerated water for injections (between 2 °C and 8 °C). Below is information on the storage of the reconstituted medicine.

1. Assemble the following items:
   Vial(s) of azacitidine; vial(s) of water for injections; non-sterile surgical gloves; alcohol-impregnated wipes; 5 ml syringes with needles.

2. Draw up 4 ml of water for injections into the syringe, ensuring that any air trapped in the syringe is purged.

3. Insert the needle of the syringe containing 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 suspension should 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 air trapped in the syringe is purged. 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. Do not purge the needle 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 the preparation of the suspension. For doses requiring more than one vial, the dose should be divided into equal parts; for example, a 150 mg dose = 6 ml; two syringes with 3 ml each. 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 should be resuspended immediately before administration. The injection suspension temperature should be approximately 20 °C to 25 °C at the time of administration. To resuspend, roll the syringe vigorously between the palms of the hands until a uniform cloudy suspension is obtained. The suspension should be discarded if large particles or clumps are present.

Storage of the reconstituted medicine

For immediate use

The azacitidine suspension may be prepared immediately before use, and the reconstituted suspension should be administered within 45 minutes. If more than 45 minutes elapse, the reconstituted suspension must be properly discarded and a new dose prepared.

For later use

When reconstituted with unrefrigerated water for injections, the reconstituted suspension must be placed in a refrigerator (between 2 °C and 8 °C) immediately after reconstitution and stored refrigerated for a maximum of 8 hours. If the refrigerated storage time exceeds 8 hours, the suspension must be properly discarded and a new dose prepared.

When reconstituted with refrigerated water for injections (between 2 °C and 8 °C), the reconstituted suspension must be placed in a refrigerator (between 2 °C and 8 °C) immediately after reconstitution and stored refrigerated for a maximum of 22 hours. If the refrigerated storage time exceeds 22 hours, the suspension must be properly discarded and a new dose prepared.

The syringe containing the reconstituted suspension should be allowed to reach a temperature of approximately 20 °C to 25 °C for a maximum of 30 minutes before administration. If more than 30 minutes elapse, the suspension must be properly discarded and a new dose prepared.

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 as an example only for calculating individual doses of azacitidine, based on an average BSA of 1.8 m².

Route of administration

Do not filter the suspension after reconstitution.

Reconstituted azacitidine must be administered by subcutaneous injection (insert the needle at an angle of 45 to 90°) using a 25-gauge needle into the 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 areas that are tender, bruised, red, or hardened.

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