AZACITIDINE SEACROSS 25 mg/mL POWDER FOR INJECTABLE SUSPENSION

Introduction

Package Leaflet: Information for the User

Azacitidina Seacross 25 mg/ml powder for injectable suspension EFG

azacitidina

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 further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Azacitidina Seacross and what is it used for
2. What you need to know before you use Azacitidina Seacross
3. How to use Azacitidina Seacross
4. Possible side effects

5 Conservation of Azacitidina Seacross

1. Contents of the pack and additional information

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

What is Azacitidina Seacross

Azacitidina is an anticancer agent that belongs to a group of medicines called "antimetabolites". This medicine contains the active substance "azacitidina".

What is Azacitidina Seacross 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 with the normal production of blood cells.

How Azacitidina Seacross 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 work 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.

Ask your doctor or nurse if you have any questions about how Azacitidina works or why you have been prescribed this medicine.

2. What you need to know before you use Azacitidina Seacross

Do not use Azacitidina Seacross

• If you are allergic to azacitidina or any of the other ingredients of this medicine (listed in section 6).
• If you have advanced liver cancer.
• During breast-feeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Azacitidina:

• If you have a low platelet count, 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 heart attack, or have a history of lung disease.

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

Blood tests

Before starting treatment with Azacitidina and at the start of each treatment period (called a "cycle"), you will have blood tests. This is to check that you have enough blood cells and that your liver and kidneys are working properly.

Children and adolescents

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

Other medicines and Azacitidina Seacross

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This is because Azacitidina may affect the way other medicines work. Similarly, other medicines may affect the way Azacitidina works.

Pregnancy, breast-feeding, and fertility

Pregnancy

Do not use Azacitidina during pregnancy because it may harm the baby.

If you are a woman who can become pregnant, you must use an effective contraceptive method while taking Azacitidina Seacross and for 6 months after finishing treatment with Azacitidina Seacross.

Tell your doctor immediately if you become pregnant during treatment.

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, ask your doctor or pharmacist for advice before using this medicine.

Breast-feeding

Azacitidina must not be used during breast-feeding. It is not known whether this medicine is excreted in breast milk.

Fertility

Men must not father a child while receiving treatment with Azacitidina. Men must use an effective contraceptive method while taking Azacitidina Seacross and for 3 months after finishing treatment with Azacitidina Seacross.

Ask your doctor if you want to preserve your sperm before you are given this treatment.

Driving and using machines

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

3. How to use Azacitidina Seacross

Before administering Azacitidina, your doctor will give you another medicine to prevent nausea and vomiting at the start of each treatment cycle.

• The recommended dose is 75 mg/m2 of body surface area. Your doctor will decide your dose of this medicine based on your general condition, height, and weight. Your doctor will monitor your progress and, if necessary, may change your dose.

• Azacitidina is given every day for a week, followed by a 3-week rest period. This "treatment cycle" is repeated every 4 weeks. You will usually receive at least 6 cycles of treatment.

A doctor or nurse will give you this medicine as an injection under the skin (subcutaneously). 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 side effects

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

Tell your doctor immediately if you notice any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and easy bruising. These can be symptoms of liver failure and can be life-threatening.
• Swelling of the legs and feet, back pain, decreased urine output, increased thirst, rapid pulse, dizziness, and nausea, vomiting, or decreased appetite and feeling of confusion, restlessness, or fatigue. These can be symptoms of kidney failure and can be life-threatening.
• Fever. This could be due to an infection as a result of having low white blood cell counts, which can be life-threatening.
• Chest pain or difficulty breathing that may be accompanied by fever. This may be due to a lung infection known as "pneumonia" and can be life-threatening.
• Bleeding. For example, blood in the stool due to bleeding in the stomach or intestines, or bleeding in the head.
• Difficulty breathing, swelling of the lips, itching, or skin rash. These can be due to an allergic reaction (hypersensitivity).

Other side effects include:

Very common side effects(may affect more than 1 in 10 people)

• Low red blood cell count (anemia). You may feel tired and pale.
• Low 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.
• Fatigue (fatigue).
• Reaction at the injection site, including redness, pain, or skin rash.
• Loss of appetite.
• Joint pain.
• Bruising.
• Skin rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Sore throat and nose.
• Dizziness.
• Headache.
• Sleep problems (insomnia).
• Nosebleeds (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). This may be due to low white blood cell counts in the blood.
• Bone marrow failure. This can cause low red and white blood cell counts and platelets.
• A type of anemia where there is a decrease in red and white blood cells and platelets.
• Urinary tract infection.
• A viral infection that causes herpes-like lesions.
• Bleeding from the gums, stomach, or intestine, bleeding in the lower back due to hemorrhoidal bleeding, bleeding in the eyes, bleeding under the skin or within the skin (hematoma).
• Blood in the urine.
• Ulcers in the mouth or tongue.
• Changes in the skin at the injection site. These can 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).
• Nose and throat infection, or sore throat.
• Pain or excessive discharge from the nose or sinuses (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing when moving.
• Pain in the throat and larynx.
• Indigestion.
• Drowsiness (lethargy).
• Feeling unwell.
• Anxiety.
• Feeling confused.
• Hair loss.
• Kidney failure.
• Dehydration.
• A white coating on the tongue, inside of the cheeks, and sometimes the palate, gums, and tonsils (fungal infection in the mouth).
• Fainting.
• Low blood pressure when standing up (orthostatic hypotension) that causes dizziness when standing up or sitting.
• Sleepiness, drowsiness (somnolence).
• Bleeding due to the catheter route.
• A disease that affects the intestine that can cause fever, vomiting, and abdominal pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills (shivering).
• Muscle spasms.
• Itchy skin rash (urticaria).
• Fluid around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Painful, large, and swollen purple spots on the skin and fever.
• Painful ulcers on the skin (pyoderma gangrenosum).
• Inflammation of the lining that surrounds the heart (pericarditis).

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

• Dry cough.
• Painful swelling of the fingertips (drumstick fingers).
• Tumor lysis syndrome - metabolic complications can occur during cancer treatment and sometimes even without treatment. These complications occur as a result of the product of dying tumor cells and can include: changes in blood biochemistry, high levels of potassium, phosphorus, uric acid, and low levels of calcium, which can cause changes in kidney function and heart rhythm, seizures, and sometimes death.

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

• Infection of the deep layers of the skin that spreads rapidly, damaging the skin and tissue, which can be life-threatening (necrotizing fasciitis).
• Severe immune reaction (differentiation syndrome) that can cause fever, cough, difficulty breathing, skin rash, decreased urine output, low blood pressure (hypotension), swelling of the arms or legs, and rapid weight gain.
• Inflammation of blood vessels in the skin that can cause skin rash (cutaneous vasculitis).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Azacitidina Seacross

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

Do not use this medicine after the expiry date which is stated on the label of the vial and on the carton, after EXP. The expiry date is the last day of the month shown.

Your doctor, pharmacist, or nurse is responsible for the conservation of Azacitidina Seacross. They are also responsible for the correct preparation and disposal of the medicine that is not used.

Unopened vials

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

Reconstituted suspension

If used immediately

The suspension must be administered within 45 minutes of preparation.

If used later

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

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

The suspension must be allowed to reach room temperature (20°C to 25°C) before administration.

The suspension must be discarded if it contains large particles.

6. Container Contents and Additional Information

Azacitidina Seacross Composition

• The active ingredient is azacitidine. One vial contains 100 mg of azacitidine. After reconstitution with 4 ml of water for injectable preparations, the reconstituted suspension contains 25 mg/ml of azacitidine.
• The other component is mannitol (E421).

Product Appearance and Container Contents

Azacitidina Seacross is a white to almost white lyophilized powder for injectable suspension and is supplied in a glass vial containing 100 mg of azacitidine. It is packaged in a Type I, colorless glass vial, sealed with a butyl rubber stopper and an aluminum cap with a plastic button. Each container contains one vial of Azacitidina.

Marketing Authorization Holder

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

Manufacturer

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

You can request more information about this medication by contacting the Local Representative of the marketing authorization holder:

Local Representative:

Sun Pharma Laboratorios, S.L.

Rambla de Catalunya 53-55

08007 – Barcelona

Spain

Tel.: +34 93 342 78 90

Date of the Last Revision of this Prospectus:November 2023

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

There are also links to other websites about rare diseases and orphan medicines.

This information is intended only for healthcare professionals:

Recommendations for Safe Handling

Azacitidina Seacross is a cytotoxic medication, and as with other potentially toxic compounds, caution should be exercised when handling and preparing azacitidine suspensions. The procedures for the handling and disposal of cancer medications should be applied.

If reconstituted azacitidine 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 medication should not be mixed with others, except as mentioned below (see "Reconstitution Procedure").

Reconstitution Procedure

Azacitidina Seacross should be reconstituted with water for injectable preparations. The validity period of the reconstituted medication can be extended by reconstituting it with refrigerated water for injectable preparations (between 2 °C and 8 °C). The following information is provided about the storage of the reconstituted medication.

1. The following elements should be assembled:

Vial(s) of azacitidine; vial(s) of water for injectable preparations; non-sterile surgical gloves; alcohol-soaked swabs; 5 ml syringes with needles.

1. 4 ml of water for injectable preparations should be drawn into the syringe,

ensuring that any trapped air is purged from the syringe.

1. The needle of the syringe containing the 4 ml of water for injectable preparations should be inserted through the rubber stopper of the azacitidine vial; then, the water for injectable preparations should be injected into the vial.
2. After removing 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 turbid and homogeneous suspension, without agglomerates. The suspension should be discarded if it contains large particles or agglomerates. Do not filter the suspension after reconstitution, as this could remove the active ingredient. It should be noted that some adapters, infusion needles, and closed systems contain filters; therefore, these systems should not be used for the administration of the medication after reconstitution.
3. The rubber stopper should be cleaned, and a new syringe with a needle should be inserted 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 required amount of medication for the correct dose, ensuring that any trapped air is purged from the syringe. Then, the syringe with the needle should be removed from the vial, and the needle should be discarded.
4. A new subcutaneous needle (25 gauge recommended) for injectables should be firmly attached to the syringe. The needle should not be purged before injection to reduce the incidence of local reactions at the injection site.
5. If more than one vial is needed, all the previous steps should be repeated for the preparation of the suspension. In the case of doses that require more than one vial, the dose should be divided into equal parts, for example, a dose of 150 mg = 6 ml; two 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.

1. The contents of the dosing syringe should be resuspended immediately before administration. The syringe loaded with 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 the time elapsed is more than 30 minutes, the suspension should be discarded correctly, and a new dose should be prepared. To resuspend, vigorously roll the syringe between the palms of the hands until a uniform, turbid suspension is obtained. The suspension should be discarded if it contains large particles or agglomerates.

Storage of the Reconstituted Medication

For Immediate Use

The Azacitidina Seacross suspension can be prepared immediately before use, and the reconstituted suspension should be administered within the next 45 minutes. If the time elapsed is more 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 injectable preparations, the reconstituted suspension should be placed in a refrigerator (temperature between 2 °C and 8 °C) immediately after reconstitution and should be kept in the refrigerator for a maximum of 8 hours. If the time elapsed in the refrigerator is more than 8 hours, the suspension should be discarded correctly, and a new dose should be prepared.

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

The syringe loaded with 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 the time elapsed is more 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 (BSA), can be calculated as follows:

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

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

Administration Method

Do not filter the suspension after reconstitution.

Reconstituted Azacitidina Seacross should be injected subcutaneously (insert the needle at an angle of 45 to 90°), with a 25-gauge needle, in the arm, thigh, or abdomen.

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

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 disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.