AZACITIDINA 25 mg /Ml Порошок Для Инъекционной Суспензии

Содержание инструкции

1. Azacitidina Seacross 25 mg/mL powder for injectable suspension
   1. What is Azacitidina Seacross and what is it 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

Azacitidina Seacross 25 mg/mL powder for injectable suspension

Azacitidina

Equivalent medicine

Read this leaflet carefully before you start to 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 Seacross is and what it is used for
• 2. What you need to know before you use 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 is Azacitidina Seacross and what is it used for

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

What is Azacitidina Seacross used for
Azacitidina Seacross 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 Seacross works
Azacitidina Seacross 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
thought 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 Seacross works or why it 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 stage liver cancer.
• if you are breastfeeding.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Azacitidina Seacross:

• 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. If you notice signs of bleeding, if you have a fever or if you experience a reduced frequency of urination, tell your doctor immediately. See also section 4.

Blood tests
Before starting treatment with Azacitidina Seacross 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 Seacross is not recommended in children and adolescents under 18
years of age.

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

Pregnancy, breastfeeding and fertility
Pregnancy
You should not use Azacitidina Seacross during pregnancy, as it may be harmful to the baby.
Use effective contraception during and up to 3 months after treatment.
Tell your doctor immediately if you become pregnant during treatment.
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.
Breastfeeding
You should not breastfeed while using Azacitidina Seacross. It is not known whether this medicine passes into
breast milk.
Fertility
During treatment with Azacitidina Seacross, male patients should not father a
child. Use effective contraception during and up to 3 months after treatment with
this medicine.
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 Seacross

Before administering Azacitidina Seacross, 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 Seacross is administered daily for one week, followed by a 3-week break. This “treatment cycle” will be repeated every 4 weeks. Generally, 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 consult your doctor, pharmacist or
nurse.

4. Possible side effects

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

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

• Sleepiness, tremor, jaundice, abdominal swelling and easy bruising. These may be symptoms of liver failure and can be life-threatening.
• Swollen legs and feet, back pain, decreased urination, increased thirst, rapid pulse, dizziness and nausea, vomiting or reduced 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 intestine, or bleeding inside the head. These may be symptoms of low platelet levels in the blood.
• Difficulty breathing, swollen 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 in the blood (thrombocytopenia). You are more likely to bleed and bruise.
• 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, anorexia.
• Joint pain.
• Bruising.
• Skin rash.
• Red or purple spots under the skin.
• Abdominal pain (stomach pain).
• Itching.
• Fever.
• Irritation of the nose and throat.
• Dizziness.
• Headache.
• Difficulty sleeping (insomnia).
• Nosebleeds (epistaxis).
• Muscle and bone pain (including back, bones and limb pain).
• Weakness (asthenia).
• Weight loss.
• Low levels of potassium 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 irritations (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.
• Inflammation in the mouth or on the tongue (stomatitis).
• Skin changes at the injection site, including swelling, hard lump, bruising, blood under the skin (hematoma), rash, itching and changes in skin color.
• Redness of the skin (erythema), purple spots on the skin (purpura), flat rash (macular rash).
• Skin infection, inflammation of the connective tissue under the skin (cellulitis).
• Infection of the nose and throat, or sore throat or inflammation of the pharynx (upper respiratory tract infection).
• Bronchitis.
• Irritated nose or sinuses (rhinitis) or runny nose (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Shortness of breath during exertion.
• 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 rash on the skin that causes itching (urticaria).
• Fluid collection around the heart (pericardial effusion).
• Muscle pain (myalgia).
• Increased levels of creatinine in the serum (shown by laboratory tests).

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

• Allergic reaction (hypersensitivity).
• Liver failure.
• Appearance on the skin of large, raised, plum-colored patches, painful, with fever.
• Painful skin ulceration (pyoderma gangrenosum).
• Inflammation of the lining around the heart (pericarditis).
• Coma that can occur in severe cases of liver disease (progressive hepatic coma).
• Medical condition involving an accumulation of acid in the body due to the kidneys’ inability to acidify the urine adequately (renal tubular acidosis). Rare side effects(may affect up to 1 in 1,000 people)
• Dry cough (interstitial lung disease).
• 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.
• Necrosis of the injection site.

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).

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in
this leaflet. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects you can help
provide more information on the safety of this medicine.

5. How to store Azacitidina Seacross

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

For immediate use
Once prepared, the suspension must be administered within 45 minutes and the storage temperature must not exceed 25°C.

For subsequent use
If Azacitidina Seacross suspension is reconstituted with non-refrigerated water for injections, 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 Azacitidina Seacross suspension 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 Seacross 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 component is mannitol (E421).

Description of the appearance of Azacitidina Seacross and contents of the pack
Azacitidina Seacross is a white to almost white lyophilized powder for injectable suspension,
supplied in a colorless glass vial sealed with a gray bromobutyl rubber stopper and an aluminum
tear-off cap with a green polypropylene disc containing 100 mg of azacitidine.
Each pack contains one vial of Azacitidina Seacross.

Marketing authorization holder and manufacturer
Seacross Pharma (Europe) Limited
Regus Dublin Airport
Skybridge House
Corballis Road North
Dublin Airport Swords
Co. Dublin, K67 P6K2
Ireland

This medicinal product is authorised in the Member States of the EEA with the following names:
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The following information is intended exclusively for healthcare professionals:
Recommendations for safe handling
Azacitidina Seacross is a cytotoxic medicine 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 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 Seacross 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, ensuring that any remaining air bubbles are removed from the syringe.
• 3. Insert the needle of the syringe 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, 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). The reconstituted product is a homogeneous, opaque suspension, free of aggregates. The suspension should 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 administration of the medicine 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, ensuring that the tip of the needle is below the level of the liquid. Then pull the plunger to draw up the amount of medicine needed for the correct dose, ensuring that any remaining air bubbles are removed from the syringe. Then, remove the syringe with the needle from the vial and dispose of the needle.
• 6. At this point, firmly 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 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 20ºC-25ºC. To resuspend, roll the syringe vigorously between the palms of your hands until a uniform opaque suspension is obtained. The suspension should be discarded if it contains large particles or aggregates.

Storage of the reconstituted medicine

For immediate use
The suspension of Azacitidina Seacross can be prepared immediately before use and the
reconstituted suspension must be administered within 45 minutes and the storage temperature
must not exceed 25°C. If more than 45 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
the 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 the 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.
From a microbiological point of view, the reconstituted product must be used immediately. If the
medicine is not used immediately, the user is responsible for the duration and conditions of
storage before use; the shelf life must not exceed 8 hours at temperatures
between 2 °C and 8 °C when reconstitution is carried out with non-refrigerated water for injections or must not exceed 22 hours when reconstitution is carried out with refrigerated water for
injections (2 °C-8 °C).
Before administration, wait 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.
Calculation of individual dose
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.

Method of administration
Do not filter the suspension after reconstitution.
The reconstituted solution of Azacitidina Seacross 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 the injection sites. Subsequent injections must be administered at
a distance of at least 2.5 cm from the previous site and never in sensitive, bruised, reddened or hardened areas.
Unused medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations for cytotoxic agents.