Package Insert: Information for the User

Azacitidina Accord25mg/ml powder for injectable suspension EFG

azacitidina

Read this package insert carefully beforestarting to usethis medication,because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• If you experienceadverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this package insert. See section4.

What is Azacitidina Accord

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

What is Azacitidina Accord used for

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

• High-risk myelodysplastic syndromes (SMD).
• Chronic myelomonocytic leukemia (LMMC).
• Acute myeloid leukemia (LMA).

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

How Azacitidina Accord works

Azacitidina Accord works by inhibiting 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 that kill cancer cells in leukemia.

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

No use Azacitidina Accord

• If you are allergic to azacitidina or any of the other components of this medication (listed in section6).
• If you have advanced liver cancer.
• During lactation.

Advertencias and precautions

Consult your doctor, pharmacist, or nurse before starting to useAzacitidina Accord:

• 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 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 Accord 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

The use of Azacitidina Accord is not recommended in children and adolescents under18years.

Other medications and Azacitidina Accord

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

Pregnancy, lactation, and fertility

Pregnancy

You should not use Azacitidina Accord 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 taking Azacitidina Accord and for 6 months after completing treatment with Azacitidina Accord.

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.

Lactation

Azacitidina Accord should not be used during lactation. It is unknown whether this medication is excreted in breast milk.

Fertility

Males should not conceive a child while receiving treatment with Azacitidina Accord.

Males should use an effective contraceptive method while taking Azacitidina Accord for 3 months after completing treatment with Azacitidina Accord.

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

Driving and operating machines

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

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

• The recommended dose is75mg/m2of 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 Accord 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 usually receive at least six treatment cycles.

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

If you have any other questions about the use of this medicine, 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 notice any of the following side effects:

• Drowsiness, tremors, jaundice, abdominal distension, and easy 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 may 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 than1in 10people)

• 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 getting 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, which includes 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 nasal congestion.
• 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 to1in 10people)

• 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 with decreased red and white blood cell counts and platelet counts.
• Urinary tract infection.
• A viral infection that causes herpes-like lesions.
• Bleeding from the gums, bleeding from the stomach or intestines, bleeding from the lower back due to hemorrhoidal bleeding, bleeding in the eyes, bleeding under the skin or inside the skin (hematoma).
• Blood in the urine.
• Ulcers in the mouth or tongue.
• 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.
• Skin redness.
• Skin infection (cellulitis).
• Throat and nasal congestion, or sore throat.
• Nasal or sinus congestion.
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing when moving.
• Sore throat and laryngitis.
• Indigestion.
• Drowsiness (somnolence).
• Discomfort.
• Anxiety.
• Confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• A white coating on the tongue, the inside of the cheeks, and sometimes the palate, gums, and tonsils (fungal infection of the mouth).
• 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 around the heart (pericardial effusion).

Uncommon side effects(may affect up to1in 100people)

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

Rare side effects(may affect up to1in 1,000people)

• Dry cough.
• Painless swelling 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 cancer cells and may include: changes in blood biochemistry, high potassium, phosphorus, and uric acid levels, and low calcium levels that, therefore, generate changes in kidney function and heart rhythm, seizures, 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 of side effects

If you experienceanytype of side effect,consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through thenational reporting systemincluded in theAppendix V. 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 medication after the expiration date that appears on the vial label and on the box. The expiration date is the last day of the month indicated.

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

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

If used later

If the Azacitidina Accord suspension is prepared using non-refrigerated injectable water, the suspension should be placed in the refrigerator (between2°C and8°C) immediately after preparation and should be stored in the refrigerator for8hours maximum.

If the Azacitidina Accord suspension is prepared using refrigerated injectable water (between2°C and8°C), the suspension should be placed in the refrigerator (between2°C and8°C) immediately after preparation and should be stored in the refrigerator for22hours maximum.

The suspension should be allowed to reach an ambient temperature of20°C to25°Cfor a maximum time of30minutesbefore administration.

The suspension should be discarded if it contains large particles.

Composition of Azacitidina Accord

• The active ingredient is azacitidina. A vial contains100mg of azacitidina. After reconstitution with4ml of water for injection, the reconstituted suspension contains25mg/ml of azacitidina..
• The other component is mannitol (E421).

Appearance of the product and contents of the pack

Azacitidina Accord is a white powder for injection and is delivered in a glass vial containing100mg of azacitidina. Each pack contains one vial of Azacitidina Accord.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center,

Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona, Spain

Responsible Person

O

Accord Healthcare Polska Sp.z o.o.

ul. Lutomierska 50,

95-200 Pabianice

Poland

O

Laboratori Fundació Dau

C/ C, 12-14 Pol. Ind.

Zona Franca, Barcelona, 08040,

Spain

O

Accord Healthcare B.V.

Winthontlaan, 200

3526 KV Utrecht

Netherlands

Last review date of this leaflet:{MM/AAAA}.

Further information is available on the website of the European Medicines Agency:

http://www.ema.europa.eu/. Links to other websites on rare diseases and orphan medicines are also available.

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