Azacitidine Seacross 25 mg/ml powder for injectable suspension EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Azacitidina Seacross 25 mg/ml powder for injectable suspension EFG

azacitidine

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

What Azacitidine Seacross is

Azacitidine is an anticancer agent belonging to a group of medicines called "antimetabolites". This medicine contains the active substance "azacitidine".

What Azacitidine Seacross is used for

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

• Higher-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 Azacitidine Seacross works

Azacitidine works by inhibiting 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 defects in maturation and growth of healthy blood cells in the bone marrow caused by myelodysplastic disorders, and to kill cancer cells in leukaemia.

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 Seacross

Do not use Azacitidina Seacross

• 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.
• During breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Azacitidina Seacross:

• 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, myocardial infarction, or have a history of lung disease.

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

Blood tests

Before starting treatment with Azacitidina and at the beginning of each treatment period (called a "cycle"), you will have blood tests. These tests are performed to ensure you have sufficient blood cells and that your liver and kidneys are functioning properly.

Children and adolescents

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

Other medicines and Azacitidina Seacross

Inform 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 Azacitidina during pregnancy because it may harm the unborn baby.

If you are a woman of childbearing potential, you must use an effective method of contraception during treatment with Azacitidina Seacross and for 6 months after completing treatment with Azacitidina Seacross.

Inform your doctor immediately if you become pregnant during treatment.

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

Breastfeeding

Azacitidina must not be used during breastfeeding. It is unknown whether this medicine is excreted in breast milk.

Fertility

Men must not father a child while receiving treatment with Azacitidina. Men should use an effective method of contraception during treatment with Azacitidina Seacross and for 3 months after completing treatment with Azacitidina Seacross.

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

Driving and use of machines

Do not drive or operate tools or machinery if you experience adverse 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 beginning of each treatment cycle.

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

• Azacitidina 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 may 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 and can be potentially fatal.
• Swelling of legs and feet, back pain, decreased urine output, increased thirst, rapid pulse, dizziness and nausea, vomiting or loss of appetite, and feeling confused, restless, or fatigued. These may be symptoms of kidney failure and can be potentially fatal.
• Fever. This could be due to an infection caused by low levels of white blood cells, which can be potentially fatal.
• Chest pain or difficulty breathing, which may be 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 bleeding inside the head. These may be symptoms of low platelet levels 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.
• Nasal and throat pain.
• Dizziness.
• Headache.
• Trouble sleeping (insomnia).
• Nosebleeds (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

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

• Bleeding inside the head.
• Blood infection caused by bacteria (sepsis). This may be due to low levels of white blood cells 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 sores.
• Bleeding from the gums, stomach or intestinal bleeding, bleeding in the lower back due to hemorrhoidal bleeding, eye bleeding, or bleeding under or into the skin (hematoma).
• Blood in the urine.
• Ulcers in the mouth or tongue.
• Skin changes at the injection site. These may include 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).
• Nasal or throat infection, or sore throat.
• Nasal or sinus pain or discharge (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.
• 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.
• 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 (drumstick fingers).
• Tumor lysis syndrome – metabolic complications may occur during cancer treatment and sometimes even without treatment. These complications arise from the products of dying tumor cells and may include: changes in blood biochemistry, high levels of potassium, phosphate, 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)

• Severe skin infection affecting deep layers of the skin, spreading rapidly and 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, decreased 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 can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Azacitidine Seacross

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

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

Your doctor, pharmacist, or nurse is responsible for the storage of Azacitidine Seacross, as well as for the correct preparation and disposal of any unused medicine.

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 subsequently

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

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

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

The suspension must be discarded if it contains large particles.

6. Contents of the container and other information

Composition of Azacitidina Seacross

• The active substance 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).

Appearance of the product and contents of the container

Azacitidina Seacross is a white to almost white lyophilized powder for injectable suspension, 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 pack 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

For further information about this medicinal product, please contact the Marketing Authorization Holder's Local Representative:

Local Representative:
Sun Pharma Laboratorios, S.L.
Rambla de Catalunya 53-55
08007 – Barcelona
Spain
Tel.: +34 93 342 78 90

Date of latest review of this leaflet: November 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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

This information is intended for healthcare professionals only:

Recommendations for safe handling

Azacitidina Seacross is a cytotoxic medicinal product and, as with other potentially toxic compounds, caution must be exercised when handling and preparing azacitidine suspensions. Procedures for the proper handling and disposal of anticancer medicinal products must be followed.

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

Incompatibilities

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

Reconstitution procedure

Azacitidina Seacross must be reconstituted with water for injectable preparations. The shelf life of the reconstituted medicinal product can be extended by using refrigerated water for injectable preparations (between 2 °C and 8 °C). Below is information on storage of the reconstituted medicinal product.

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

2. Draw 4 ml of water for injectable preparations 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 injectable preparations through the rubber stopper of the azacitidine vial; then inject the water for injectable preparations 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 must 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, perfusion needles, and closed systems contain filters; therefore, such systems must not be used for administering the medicinal product after reconstitution.

5. Clean the rubber stopper and insert a new syringe with a needle into the vial. Invert the vial, ensuring the needle tip is below the liquid level. Then pull back the plunger to withdraw the required amount of medicinal product for the correct dose, ensuring that any air trapped in the syringe is purged. Then 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. The needle must not be purged 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 preparing 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 in 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 must be resuspended immediately before administration. Allow the syringe filled with the reconstituted suspension 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. To resuspend, roll the syringe vigorously between the palms of the hands until a uniform cloudy suspension is obtained. The suspension must be discarded if large particles or clumps are present.

Storage of the reconstituted medicinal product

For immediate use

The Azacitidina Seacross suspension may be prepared immediately before use, and the reconstituted suspension must 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 non-refrigerated water for injectable preparations, the reconstituted suspension must be placed in a refrigerator (2 °C to 8 °C) immediately after reconstitution and stored in the refrigerator for a maximum of 8 hours. If the time in the refrigerator exceeds 8 hours, the suspension must be properly discarded and a new dose prepared.

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

Allow the syringe filled with the reconstituted suspension 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 only as an example to calculate individual azacitidine doses, based on an average BSA of 1.8 m².

Route of administration

Do not filter the suspension after reconstitution.

Reconstituted Azacitidina Seacross must be injected subcutaneously (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 should be administered at two separate injection sites.

Injection sites should be rotated. New injections must be administered at least 2.5 cm away from the previous site and never into sensitive, bruised, red, or hardened areas.

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