AZACITIDINA 25 mg /Ml Порошок Для Инъекционной Суспензии

Содержание инструкции

1. Azacitidina Accord 25 mg/mL powder for injectable suspension
   1. What is Azacitidina Accord and what is it used for
   2. What you need to know before using Azacitidina Accord
   3. How to use Azacitidina Accord
   4. Possible side effects
   5. How to store Azacitidina Accord
   6. Contents of the pack and other information

Azacitidina Accord 25 mg/mL powder for injectable suspension

azacitidina

Read this leaflet carefully before you use this medicine as 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.
• If you get any side effects, see section 4, contact your doctor, pharmacist or nurse.

Contents of this leaflet:

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

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

What is Azacitidina Accord
Azacitidina Accord is an anticancer agent that belongs to a group of medicines called
“antimetabolites”. Azacitidina Accord contains the active substance “azacitidine”.

What is Azacitidina Accord used for
Azacitidina Accord is used in adults who are not able to receive stem cell
transplantation for the treatment of:

• 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 Accord works
Azacitidina Accord works by preventing cancer cells from growing. Azacitidine is incorporated
into the genetic material of cells (ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)).
It is believed to work by altering the way the cell activates and deactivates genes and also interfering
with the production of new RNA and DNA. These actions are thought to correct the problems related to
the maturation and growth of young blood cells in the bone marrow, which cause myelodysplastic disorders,
and to kill cancer cells in leukemia.
Ask your doctor or nurse if you have any questions about how Azacitidina Accord works
or why it has been prescribed for you.

2. What you need to know before using Azacitidina Accord

Do not use Azacitidina Accord

• if you are allergic to azacitidine or 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 Azacitidina Accord:

• if you have a reduced platelet count, red blood cells or white blood cells;
• if you have kidney disease;
• if you have liver disease;
• if you have had heart disease or a heart attack in the past or if you have a history of lung disease.

Azacitidina Accord can cause a serious 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 a “cycle”) blood tests will be performed to check if you have a sufficient number of blood cells and if your liver and kidneys are functioning normally.

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

Other medicines and Azacitidina Accord
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines. This is because Azacitidina Accord can affect the way other medicines work.
Other medicines can, in turn, affect the way Azacitidina Accord works.

Pregnancy, breastfeeding and fertility
Pregnancy
You must not use Azacitidina Accord during pregnancy, as it may be harmful to the baby.
If you are a woman of childbearing potential, you must use effective contraception during treatment
with Azacitidina Accord and for 6 months after stopping treatment with Azacitidina Accord.
Tell your doctor immediately if you become pregnant during treatment with
Azacitidina Accord.
If you are pregnant, suspect you may be pregnant, are planning to become pregnant or are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.
Breastfeeding
You must not breastfeed when using Azacitidina Accord. It is not known whether this medicine passes into
breast milk.
Fertility
During treatment with Azacitidina Accord, male patients must not father a
child. Men must use effective contraception while taking Azacitidina
Accord and for 3 months after stopping treatment with Azacitidina Accord.
Consult your doctor if you wish to preserve sperm before starting this treatment.

Driving and using machines
Do not drive and do not use tools or machines if you experience side effects, such as fatigue.

3. How to use Azacitidina Accord

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 is 75 mg per m of body surface area. Your doctor will decide the dose of this medicine depending on your general condition, height and body weight. Your doctor will monitor your progress and, if necessary, will modify the dose.
• Azacitidina Accord is administered daily for one week, followed by a 3-week break. This “treatment cycle” will be repeated every 4 weeks. Usually, at least 6 treatment cycles are administered.

This medicine will be administered to you by a doctor or nurse via injection under the
skin (subcutaneous). The injection can be given under the skin of the thigh, abdomen or
upper arm.
If you have any doubts about the use of this medicine, please contact your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Seek immediate medical attention if you notice any of the following side effects:

• Drowsiness, tremor, jaundice, abdominal swelling and easy bruising.These may 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 confusion, restlessness or fatigue.These may be symptoms of kidney failure and can be life-threatening.
• Fever.This may be due to an infection caused by a reduced number of white blood cells, which can be life-threatening.
• Chest pain or shortness of breath, possibly accompanied by fever.This may be due to a lung infection called "pneumonia" and can be life-threatening.
• Bleeding.For example, blood in the stool 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 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 weak.
• 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, shortness of breath.
• Fatigue (tiredness).
• Reaction at the injection site, with redness, pain, or skin reaction.
• Loss of appetite.
• Joint pain.
• Bruising.
• Skin rash.
• Small red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Irritation of the nose and throat.
• Dizziness.
• Headache.
• Difficulty sleeping (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 inside the head.
• Blood infection due to bacteria (sepsis), which may be caused by a reduced number of white blood cells in the blood.
• Bone marrow failure, which can cause a reduction in the number of red blood cells, white blood cells, and platelets.
• A type of anemia with a reduction in red blood cells, white blood cells, and platelets.
• Urinary tract infection.
• Viral infection causing irritation (herpes).
• Bleeding gums, blood in the stomach or intestines, blood from the anus due to hemorrhoids (hemorrhoidal bleeding), blood in the eye, blood under the skin or in the skin (hematoma).
• Blood in the urine.
• Ulcers in the mouth or on the tongue.
• Skin changes at the injection site, including swelling, hard lump, bruising, blood in the skin (hematoma), rash, itching, and changes in skin color.
• Skin redness.
• Skin infection (cellulitis).
• Infection of the nose and throat, or sore throat.
• Irritated or runny nose and sinuses (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath during exertion.
• Sore throat and larynx.
• Indigestion.
• Lethargy.
• General feeling of discomfort.
• Anxiety.
• Confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• White coating on the tongue, inside of the cheeks, and sometimes the palate, gums, and tonsils (oral fungal infection).
• Fainting.
• Drop in blood pressure when standing up (orthostatic hypotension), causing dizziness when standing up or sitting down.
• Drowsiness, torpor (somnolence).
• Bleeding from the catheter.
• Disease affecting the intestine and can cause fever, vomiting, and stomach pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills (tremors).
• Muscle spasms.
• Raised, itchy rash on the skin (urticaria).
• Fluid collection around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremor.
• Liver failure.
• Appearance on the skin of large, raised, painful, plum-colored patches, with fever.
• Painful skin ulceration (pyoderma gangrenosum).
• Inflammation of the lining around the heart (pericarditis).

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

• Dry cough.
• Painless swelling of the fingertips (clubbing).
• Tumor lysis syndrome - metabolic complications that can occur during cancer treatment and sometimes even in the absence of treatment. These complications are caused by the product of dying cancer cells and can include the following complications: changes in hematological parameters; high levels of potassium, phosphorus and uric acid; and low levels of calcium leading, consequently, to changes in kidney function, heartbeat, seizures and, sometimes, death.

Not known(frequency cannot be estimated from available data)

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

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Azacitidina Accord

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. The expiry date refers to the last day of that month.
The doctor, pharmacist or nurse are responsible for the storage of Azacitidina Accord,
the preparation and the correct disposal of unused medicine.
For closed vials of this medicine - no particular storage conditions are required.

For immediate use
Once prepared, the suspension must be administered within 60 minutes.

For subsequent use
If the suspension of Azacitidina Accord is reconstituted with water for injections not
refrigerated, the suspension must be placed in a refrigerator (2 °C − 8 °C) immediately after preparation and
kept in a refrigerator for a maximum of 8 hours.
If the suspension of Azacitidina Accord is reconstituted with refrigerated water for injections
(2 °C − 8 °C), the reconstituted suspension must be placed in a refrigerator (2 °C − 8 °C) immediately
after preparation and kept in a refrigerator for a maximum of 22 hours.
Before administration, wait up to 30 minutes for the suspension to reach
room temperature (20 °C-25 °C).
The suspension must be discarded if large particles are present.

6. Contents of the pack and other information

What Azacitidina Accord contains

• The active substance is azacitidine. One vial contains 100 mg or 150 mg of azacitidine. After reconstitution with 4 mL or 6 mL of water for injections, the reconstituted suspension contains 25 mg/mL of azacitidine.
• The other component is mannitol (E421).

Description of the appearance of Azacitidina Accord and contents of the pack
Azacitidina Accord is a white powder for injectable suspension, supplied in a glass vial
containing 100 mg or 150 mg of azacitidine.
Pack sizes
1 vial containing 100 mg of Azacitidina.
1 vial containing 150 mg of Azacitidina.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona, Spain

Manufacturer
Accord Healthcare Polska Sp.z o.o.
ul. Lutomierska 50,
95-200 Pabianice
Poland
Or
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind.
Zona Franca, Barcelona, 08040,
Spain
Or
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
Netherlands
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:
AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LX / MT / NL /
NO / PT / PL / RO / SE / SI / SK / ES
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Pharmaceutical S.A.
Tel: : +30 210 7488 821
More detailed information on this medicinal product is available on the website of the European
Medicines Agency, http://www.ema.europa.eu/. Additionally, links to other websites on rare diseases
and related therapeutic treatments are provided.
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The following information is intended exclusively for healthcare professionals:
Recommendations for safe handling
Azacitidina Accord is a cytotoxic medicinal product and therefore, as with other potentially toxic
compounds, caution should be exercised during handling and preparation of azacitidine suspensions. Appropriate procedures for handling and disposal of antineoplastic medicinal products must be used.
In case of contact of reconstituted azacitidine with the skin, wash immediately and thoroughly with
water and soap. In case of contact with mucous membranes, rinse thoroughly with water.
Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned below (see paragraph “Procedure for reconstitution”).
Procedure for reconstitution
Azacitidina Accord must be reconstituted with water for injections. The shelf life of the reconstituted
medicinal product can be prolonged if reconstitution is carried out with refrigerated water for
injections (2 °C-8 °C). Details on the storage of the reconstituted medicinal product are provided below.

• 1. Prepare the following: vial(s) of azacitidine; vial(s) of water for injections; non-sterile surgical gloves; alcohol swabs; syringe(s) for injection 5 mL with needle(s).
• 2. Aspirate the appropriate volume of water for injections into the syringe, ensuring that any air bubbles remaining in the syringe are eliminated.
• 3. Insert the needle of the syringe containing water for injections into the rubber stopper of the azacitidine vial and then inject the water for injections into the vial.
• 4. After removing the syringe and needle, shake the vial vigorously until a uniform opaque suspension is formed. After reconstitution, each mL of the suspension will contain 25 mg of azacitidine (100 mg/4 mL or 150 mg/6 mL). The reconstituted product is a homogeneous, opaque suspension, free of aggregates. The suspension must be discarded if it contains large particles or aggregates. Do not filter the suspension after reconstitution as this may remove the active substance. It should be noted that some adapters, needles and closed systems contain filters; therefore, such systems should not be used for administering the medicinal product after reconstitution.
• 5. Clean the rubber stopper and insert a new syringe with a needle already mounted into the vial. Turn the vial upside down, making sure that the tip of the needle is below the level of the liquid.

Then pull the plunger to draw up the amount of medicinal product needed for the correct dose,
making sure to eliminate any air bubbles remaining in the syringe. Then, remove
the syringe with the needle from the vial and dispose of the needle.

• 6. At this point, securely attach a new needle for subcutaneous use to the syringe (the use of 25 gauge needles is recommended). The suspension should not be pushed into the needle before injection, in order to reduce the incidence of local reactions at the injection site.
• 7. When more than 1 vial is needed, repeat the steps described for preparing the suspension. For doses requiring more than 1 vial, divide the dose equally (e.g. 150 mg dose = 6 mL, 2 syringes with 3 mL each). Due to retention in the vial and needle, it may not be possible to draw up all the suspension from the vial.
• 8. The contents of the dosing syringe must be resuspended immediately before administration. The temperature of the suspension at the time of injection should be approximately 20 ºC-25 ºC. To resuspend, roll the syringe vigorously between the palms of your hands until a uniform opaque suspension is obtained. The suspension must be discarded if it contains large particles or aggregates.

Storage of the reconstituted medicinal product

For immediate use
The suspension of Azacitidina Accord can be prepared immediately before use and the
reconstituted suspension must be administered within 60 minutes. If more than 60
minutes have elapsed, the reconstituted suspension must be disposed of appropriately and a new dose must
be prepared.

For subsequent use
When reconstitution is carried out with non-refrigerated water for injections, the reconstituted
suspension must be stored in a refrigerator (2 °C − 8 °C) immediately after reconstitution and kept in
refrigerator for a maximum of 8 hours. If more than 8 hours have elapsed in the refrigerator, the suspension
must be disposed of appropriately and a new dose must be prepared.
When reconstitution is carried out with refrigerated water for injections (2 °C-8 °C), the
reconstituted suspension must be stored in a refrigerator (2 °C-8 °C) immediately after reconstitution
and kept in refrigerator for a maximum of 22 hours. If more than 22 hours have elapsed in the refrigerator, the
suspension must be disposed of appropriately and a new dose must be prepared.
Before administration, allow up to 30 minutes for the syringe filled with the
reconstituted suspension to reach a temperature of approximately 20 ºC-25 ºC. If more than
30 minutes have elapsed, the suspension must be discarded and disposed of appropriately and a new dose must
be prepared.
Individual dose calculation
The total dose based on body surface area (BSA) can be calculated as follows:
Total dose (mg) = Dose (mg/m²) x BSA (m²)
The following table is only an example of how to calculate individual doses of azacitidine in
based on an average BSA of 1.8 m².

Route of administration
Do not filter the suspension after reconstitution.
The reconstituted solution of Azacitidina Accord must be injected subcutaneously (insert the needle
at an angle of 45-90°) in the upper arm, thigh or abdomen, using a
25 gauge needle.
Doses greater than 4 mL must be injected at two different sites.
Rotate injection sites. Subsequent injections must be administered at least 2.5 cm apart from the previous site and never in sensitive, bruised, reddened or hardened areas.
Disposal
Unused medicinal product and waste derived from such medicinal product must be disposed of in
accordance with local regulations.