AZACITIDINA 25 mg /Ml Порошок Для Инъекционной Суспензии

Содержание инструкции

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

Azacitidina betapharm 25 mg/mL powder for injectable suspension

azacitidine

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, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

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

What is Azacitidina betapharm used for
Azacitidina betapharm 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 does Azacitidina betapharm work
Azacitidina betapharm 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 by interfering with the production of new RNA and DNA. These actions are believed
to correct 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 betapharm works or why it has been prescribed for you.

2. What you need to know before using Azacitidina betapharm

Do not use Azacitidina betapharm

• 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 betapharm:

• 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 betapharm can cause a serious immune reaction called ‘differentiation syndrome’ (see section 4).
Blood tests
Before starting treatment with Azacitidina betapharm and at the beginning of each treatment period (called “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 betapharm is not recommended in children and adolescents under 18 years of age.

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

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You must not use Azacitidina betapharm 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 betapharm and for 6 months after stopping treatment with Azacitidina betapharm. Tell your doctor immediately if you become pregnant during treatment with Azacitidina betapharm.
Breastfeeding
You must not breastfeed while using Azacitidina betapharm. It is not known whether this medicine passes into breast milk.
Fertility
During treatment with Azacitidina betapharm, male patients must not father a child. Men must use effective contraception while taking Azacitidina betapharm and for 3 months after stopping treatment with Azacitidina betapharm.
Talk to 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 betapharm

Before administering Azacitidina betapharm, 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, modify the dose.
• Azacitidina betapharm is administered every day 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 the
upper arm.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist or
nurse.

4. Possible side effects

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

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

• Sleepiness, tremor, 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 urination, increased thirst, rapid pulse, dizziness and nausea, vomiting or reduced appetite and feeling confused, restlessness or fatigue.These can 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 intestine, or bleeding inside the head. These can 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 may also be more likely to get infections.
• Low platelet count (thrombocytopenia). You are more likely to bleed and bruise.
• Constipation, diarrhea, nausea, vomiting.
• Pneumonia.
• Chest pain, shortness of breath.
• Fatigue.
• 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 intestine, 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.
• Changes in the skin at the injection site, including swelling, hard lump, bruising, blood under 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 exercise.
• Sore throat and larynx.
• Indigestion.
• Lethargy.
• General feeling of being unwell.
• 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), which causes dizziness when standing up or sitting down.
• Sleepiness, drowsiness.
• Bleeding due to the catheter.
• Disease affecting the intestine and can cause fever, vomiting and stomach pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• 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, painful, plum-colored raised 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 of the fingers).
• 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 blood 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 the 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 urination, 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 a rash (cutaneous vasculitis).

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system listed in
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Azacitidina betapharm

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

For immediate use
Once prepared, the suspension must be administered within 45 minutes.

For subsequent use
If the Azacitidina betapharm suspension is reconstituted with non-refrigerated water for injections, the suspension must be placed in a refrigerator (between 2 °C and 8 °C) immediately after preparation
and kept in a refrigerator for a maximum of 8 hours.
If the Azacitidina betapharm suspension is reconstituted with refrigerated water for injections (between 2 °C and 8 °C), the reconstituted suspension must be placed in a refrigerator (between 2 °C and 8 °C)
immediately after preparation and kept in a refrigerator for a maximum of 22 hours.
Allow the suspension to reach room temperature (between 20 °C and 25 °C) for a maximum of
30 minutes before administration.
The suspension must be discarded if large particles are present.

6. Contents of the pack and other information

What Azacitidina betapharm contains

• The active substance is azacitidine. One vial contains 100 mg of azacitidine. After reconstitution with 4 mL of water for injections, the reconstituted suspension contains 25 mg/mL of azacitidine.
• The other ingredient is mannitol (E 421).

Description of the appearance of Azacitidina betapharm and contents of the pack
Azacitidina betapharm is a white to off-white powder for injectable suspension, supplied in a
glass vial containing 100 mg of azacitidine. Each pack contains one vial.

Marketing Authorisation Holder and Manufacturer
betapharm Arzneimittel GmbH
Kobelweg 95
86156 Augsburg
Germany
For further information on this medicinal product, please contact the local representative of the
Marketing Authorisation Holder:

België/Belgique/Belgien
betapharm Arzneimittel GmbH
Tél/Tel: + 49 821 74881 0
[email protected]

Lietuva
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

България
betapharm Arzneimittel GmbH
Teл.: +49 821 74881 0
[email protected]

Luxembourg/Luxemburg
betapharm Arzneimittel GmbH
Tél/Tel: + 49 821 74881 0
[email protected]

Česká republika
betapharm Arzneimittel GmbH
Tel: +49 821 74881 0
[email protected]

Magyarország
betapharm Arzneimittel GmbH
Tel.: + 49 821 74881 0
[email protected]

Danmark
betapharm Arzneimittel GmbH
Tlf: + 49 821 74881 0
[email protected]

Malta
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Deutschland
betapharm Arzneimittel GmbH
Kobelweg 95
86156 Augsburg
Tel: + 49 821 74881 0

Nederland
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]
[email protected]

Eesti
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Norge
betapharm Arzneimittel GmbH
Tlf: + 49 821 74881 0
[email protected]

Ελλάδα
betapharm Arzneimittel GmbH
Τηλ: + 49 821 74881 0
[email protected]

Österreich
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

España
Reddy Pharma Iberia S.A.U.
Avenida Josep Tarradellas nº 38
E-08029 Barcelona
Tel: + 34 93 355 49 16
[email protected]

Polska
betapharm Arzneimittel GmbH
Tel.: + 49 821 74881 0
[email protected]

France
Reddy Pharma SAS
9 avenue Edouard Belin
F-92500 Rueil-Malmaison
Tél: + 33 1 85 78 17 34
[email protected]

Portugal
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Hrvatska
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

România
Dr. Reddy´s Laboratories Romania SRL
Tel: + 4021 224 0032
[email protected]

Ireland
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Slovenija
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Ísland
betapharm Arzneimittel GmbH
Sími: + 49 821 74881 0
[email protected]

Slovenská republika
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Italia
Dr. Reddy’s S.r.l.
Piazza Santa Maria Beltrade, 1
I-20123 Milano
Tel: + 39(0)2 70106808
[email protected]

Suomi/Finland
betapharm Arzneimittel GmbH
Puh/Tel: + 49 821 74881 0
[email protected]

Κύπρος
betapharm Arzneimittel GmbH
Τηλ: + 49 821 74881 0
[email protected]

Sverige
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

Latvija
betapharm Arzneimittel GmbH
Tel: + 49 821 74881 0
[email protected]

United Kingdom (Northern Ireland)
Dr. Reddy's Laboratories (UK) Limited
6 Riverview Road, East Riding Of Yorkshire
HU17 0LD Beverley
Tel: + 44(0)1482 389858
[email protected]
More detailed information on this medicinal product is available on the website of the European Medicines
Agency, http://www.ema.europa.eu . . Furthermore, links to other websites on rare diseases and
related therapeutic treatments are provided.
<----------------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for healthcare professionals:
Recommendations for safe handling
Azacitidina betapharm is a cytotoxic medicine and therefore, as with other potentially toxic
compounds, caution is required during handling and preparation of azacitidine suspensions. Appropriate
procedures for handling and disposal of anti-cancer medicines must be used. If reconstituted
azacitidine comes into contact with the skin, wash immediately and thoroughly with soap and water. If
contact occurs with mucous membranes, rinse thoroughly with water.
Incompatibilities
This medicine must not be mixed with other medicines except those mentioned below (see section
“Procedure for reconstitution”).
Procedure for reconstitution
Azacitidina betapharm must be reconstituted with water for injections. The shelf life of the
reconstituted medicine can be extended if reconstitution is carried out with refrigerated water for
injections (2 °C-8 °C). Details on storage of the reconstituted medicine are provided below.

• 1. Prepare the following: vial(s) of azacitidine; vial(s) of water for injections; non-sterile surgical gloves; alcohol swabs; 5 mL injection syringe(s) with needle(s).
• 2. Draw 4 mL of water for injections into the syringe, making sure to remove any remaining air bubbles from the syringe.
• 3. Insert the syringe needle containing 4 mL of 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, vigorously shake the vial until a uniform opaque suspension is formed. After reconstitution, each mL of the suspension will contain 25 mg of azacitidine (100 mg/4 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 medicine after reconstitution.
• 5. Clean the rubber stopper and insert a new syringe with a needle already attached 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 the amount of medicine needed for the correct dose, making sure to remove any remaining air bubbles from 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 (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 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 °C-25 °C. 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 medicine

For immediate use
The suspension of Azacitidina betapharm can be prepared immediately before use and the
reconstituted suspension must be administered within 45 minutes. If more than
45 minutes have elapsed, the reconstituted suspension must be disposed of appropriately and a new dose must
be prepared.

For later use
When reconstitution is carried out with non-refrigerated water for injections, the suspension
must be stored in a refrigerator (2 °C-8 °C) immediately after reconstitution and kept in
refrigeration 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 refrigeration 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 °C-25 °C. 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) × 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.
Method of administration
Do not filter the suspension after reconstitution.
The reconstituted solution of Azacitidina betapharm must be injected subcutaneously (insert
the needle at an angle of 45-90°) into the upper arm, thigh or abdomen,
using a 25 gauge needle.

Alternate injection sites in rotation. 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 medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations.