Prospecto: information for the user

Vidaza25mg/ml powder for injectable suspension

azacitidina

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.

-If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section4.

1.What is Vidaza and for what it is used

2.What you need to know before starting to use Vidaza

3.How to use Vidaza

4.Possible adverse effects

5Storage of Vidaza

6.Contents of the package and additional information

What is Vidaza

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

How is Vidaza used

Vidaza 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 Vidaza works

Vidaza 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 kill cancer cells in leukemia.

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

No use Vidaza

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

Warnings and precautions

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

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

Vidaza may cause a severe immune reaction called “differentiation syndrome” (see section4).

Blood tests

Before starting treatment with Vidaza and at the beginning of each treatment period (called “cycle”) blood tests will be done. 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 Vidaza is not recommended in children and adolescents under18years.

Other medications and Vidaza

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

Pregnancy, lactation, and fertility

Pregnancy

You must not use Vidaza during pregnancy because it may be harmful to the baby.

If you are a woman and may become pregnant, you must use an effective contraceptive method while taking Vidaza and for 6months after finishingthe treatment with Vidaza.

Inform your doctor immediately if you become pregnant during treatment.

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

Lactation

Vidaza must not be used during lactation. It is unknown whether this medication passes into breast milk.

Fertility

Males must not conceive a child while receiving treatment with Vidaza. Men must use an effective contraceptive method while taking Vidaza and for 3months after finishing the treatment with Vidaza.

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

Driving and operating machinery

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

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 bloating, 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 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 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.
• 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 runny nose.
• Dizziness.
• Headache.
• Difficulty falling asleep (insomnia).
• Nosebleeds (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

Common side effects(may affect up to1in 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 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 infection, or sore throat.
• Pain or excessive secretion from the nose or sinuses (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing when moving.
• Sore throat and larynx.
• Indigestion.
• Drowsiness (somnolence).
• Feeling unwell.
• Anxiety.
• Feeling of confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• 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).
• Liquid around the lungs (pleural effusion).
• Chills (rigors).
• Muscle spasms.
• Skin rash with itching (urticaria).
• Liquid around the heart (pericardial effusion).

Uncommon side effects(may affect up to1in 100 people)

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Large, painful, 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 1,000 people)

• Dry cough.
• Swelling without pain of the fingertips (fingers like 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.

Frequency not known(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.

Reporting of 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 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 Vidaza. They are also responsible for the correct preparation and disposal of unused Vidaza.

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

If used immediately

The suspension must be administered within45minutes of its preparation.

If used later

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

If Vidaza suspension is prepared using refrigerated injectable water (between2°C and8°C), the suspension must be placed in the refrigerator (between2°C and8°C) immediately after preparation and must be kept in the refrigerator for22hours maximum.

Allow the suspension to reach an ambient temperature of20°C to25°Cfor a maximum of30minutes before administration.

The suspension must be discarded if it contains large particles.

Composition of Vidaza

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

Appearance of the product and contents of the package

Vidaza is a white powder for injection and is delivered in a glass vial containing100mg of azacitidine. Each package contains one vial of Vidaza.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG

254 Plaza

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible for manufacturing

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BDUtrecht

Netherlands

Last review date of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.There are also links to other websites on rare diseases and orphan medicines.

‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑