Azacitidine Mylan 25 mg/ml powder for injectable suspension EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Azacitidine Mylan 25 mg/ml powder for injectable suspension EFG

azacitidine

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

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

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

What Azacitidina Mylan is

Azacitidina Mylan is an anticancer agent belonging to a group of medicines called "antimetabolites". Azacitidina Mylan contains the active substance "azacitidine".

What Azacitidina Mylan is used for

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

• High-risk myelodysplastic syndromes (MDS).
• Chronic myelomonocytic leukaemia (CMML).
• Acute myeloid leukaemia (AML).

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

How Azacitidina Mylan works

Azacitidina Mylan works by preventing the growth of cancer cells. Azacitidine 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 switch genes on or off, through interference with the production of new RNA and DNA. These actions are thought to correct the problems in maturation and growth of healthy blood cells in the bone marrow caused by myelodysplastic disorders, and to kill cancer cells in leukaemia.

Ask your doctor or nurse if you have any questions about how Azacitidina Mylan works or why this medicine has been prescribed for you.

2. What you need to know before using Azacitidine Mylan

Do not use Azacitidine Mylan

• If you are allergic to azacitidine or to any of the other ingredients of this medicine (listed in section 6).
• If you have advanced liver cancer.
• During breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Azacitidine Mylan:

• If you have low platelet counts, red blood cells, or white blood cells.
• If you have kidney disease.
• If you have liver disease.
• If you have ever had heart disease or myocardial infarction, or have a history of lung disease.

Blood tests

Before starting treatment with Azacitidine Mylan and at the beginning of each treatment cycle, you will have blood tests. These are performed to ensure that you have sufficient blood cells and that your liver and kidneys are functioning properly.

Children and adolescents

The use of Azacitidine Mylan is not recommended in children and adolescents under 18 years of age.

Other medicines and Azacitidine Mylan

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

This is because Azacitidine Mylan may affect how other medicines work.

Likewise, other medicines may affect how Azacitidine Mylan works.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

You must not use Azacitidine Mylan during pregnancy because it may harm the unborn baby.

Use an effective method of contraception during treatment and for 3 months after treatment ends.

Inform your doctor immediately if you become pregnant during treatment.

Breastfeeding

Azacitidine Mylan must not be used during breastfeeding. It is unknown whether this medicine is excreted in human milk.

Fertility

Men must not father a child while receiving treatment with Azacitidine Mylan. Use an effective method of contraception during treatment and for 3 months after treatment ends.

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

Driving and using machines

Do not drive or operate tools or machinery if you experience adverse effects such as fatigue.

3. How to use Azacitidina Mylan

Before administering Azacitidina Mylan, 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/m² of body surface area. Your doctor will determine your dose of this medicine based on your general condition, height, and weight. Your doctor will monitor your progress and, if necessary, may adjust your dose.
• Azacitidina Mylan is administered daily for one week, followed by a 3-week rest period. This "treatment cycle" will be repeated every 4 weeks. You will usually receive at least 6 treatment cycles.

A doctor or nurse will administer this medicine as an injection under the skin (subcutaneous route). It may be given under the skin of the thigh, abdomen, or arm (above the elbow).

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Contact your doctor immediately if you notice any of the following adverse effects:

• Drowsiness, tremors, jaundice, abdominal swelling, and easy bruising. These 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 loss of appetite, and confusion, restlessness, or fatigue. These may be symptoms of kidney failure and can be potentially fatal.
• Fever. This may be due to an infection caused by low white blood cell counts, which can be potentially fatal.
• Chest pain or difficulty breathing, possibly accompanied by fever. This may be due to a lung infection known as "pneumonia" and can be potentially fatal.
• Bleeding. For example, blood in the stools 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 adverse effects include:

Very common adverse effects (may affect more than 1 in 10 people)

• Decreased red blood cell count (anemia). You may feel tired and look pale.
• Decreased white blood cell count. This may be accompanied by fever and increases your risk of infections.
• Low platelet count in the blood (thrombocytopenia). You are more likely to bleed or bruise easily.
• Constipation, diarrhea, nausea, vomiting.
• Pneumonia.
• Chest pain, difficulty breathing.
• Tiredness (fatigue).
• Reaction at the injection site, including redness, pain, or skin reaction.
• Loss of appetite.
• Joint pain.
• Bruising.
• Skin rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Trouble sleeping (insomnia).
• Nosebleeds (epistaxis).
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low blood potassium levels.

Common adverse effects (may affect up to 1 in 10 people)

• Bleeding inside the head.
• Blood infection caused by bacteria (sepsis). This may be due to low white blood cell counts.
• Bone marrow failure. This may cause low levels of red and white blood cells and platelets.
• A type of anemia characterized by reduced red and white blood cells and platelets.
• Urinary tract infection.
• A viral infection causing herpes-like sores.
• Bleeding from the gums, stomach or intestine, lower back bleeding due to hemorrhoidal bleeding, bleeding in the eyes, or bleeding under or into the skin (bruising).
• Blood in the urine.
• Mouth or tongue ulcers.
• Skin changes at the injection site, such as swelling, hard lump, bruising, bleeding into the skin (bruising), skin rash, itching, and skin color changes.
• Skin redness.
• Skin infection (cellulitis).
• Nose and throat infection, or sore throat.
• Pain or excessive nasal or sinus discharge (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing during physical activity.
• Throat and larynx pain.
• Indigestion.
• Drowsiness (lethargy).
• Feeling unwell.
• Anxiety.
• Confusion.
• Hair loss.
• Kidney failure.
• Dehydration.
• White coating covering the tongue, inside of the cheeks, and sometimes the palate, gums, and tonsils (fungal infection in the mouth).
• Fainting.
• Drop in blood pressure upon standing (orthostatic hypotension), causing dizziness when standing up or sitting down.
• Sleepiness, drowsiness (somnolence).
• Bleeding at the catheter site.
• A condition affecting the intestine that may cause fever, vomiting, and stomach pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• Muscle spasms.
• Itchy skin rash (urticaria).
• Fluid accumulation around the heart (pericardial effusion).

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

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Painful, large, raised plum-colored spots on the skin and fever.
• Painful skin ulcers (pyoderma gangrenosum).
• Inflammation of the lining surrounding the heart (pericarditis).

Rare adverse effects (may affect up to 1 in 1000 people)

• Dry cough.
• Painless swelling of the fingertips (clubbing).
• Tumor lysis syndrome: metabolic complications may occur during cancer treatment and sometimes even without treatment. These complications result from the breakdown products of dying tumor cells and may include: changes in blood biochemistry, high levels of potassium, phosphate, and uric acid, and low calcium levels, leading to changes in kidney function and heart rhythm, seizures, and sometimes death.

Frequency not known (cannot be estimated from available data)

• Deep skin layer infection that spreads rapidly, damaging skin and tissue, which may be potentially fatal (necrotizing fasciitis).

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Azacitidine Mylan

Your doctor, pharmacist, or nurse is responsible for the storage of Azacitidine Mylan. They are also responsible for the correct preparation and disposal of any unused Azacitidine Mylan.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the vial label and the carton. The expiry date refers to the last day of the month indicated.

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

If used immediately

The suspension should be administered within 1 hour after preparation.

If used later

If the Azacitidine Mylan suspension is prepared using non-refrigerated water for injections, the suspension must be placed immediately in a refrigerator (between 2 °C and 8 °C) after preparation and may be stored in the refrigerator for up to 8 hours.

If the Azacitidine Mylan suspension is prepared using refrigerated water for injections (between 2 °C and 8 °C), the suspension must be placed immediately in a refrigerator (between 2 °C and 8 °C) after preparation and may be stored in the refrigerator for up to 22 hours.

Allow the suspension to reach room temperature (20 °C to 25 °C) for 30 minutes before administration.

The suspension should be discarded if it contains large particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This helps protect the environment.

6. Contents of the container and other information

Composition of Azacitidine Mylan

• The active substance is azacitidine. One vial of powder 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 (E421).

Appearance of the product and contents of the container

Azacitidine Mylan is a white powder for injectable suspension supplied in a glass vial containing 100 mg of azacitidine. Each pack contains 1 or 7 vials.

Marketing Authorization Holder

Mylan Ireland Limited

Unit 35/36 Grange Parade

Baldoyle Industrial Estate

Dublin 13, Ireland

Manufacturer responsible

Drehm Pharma GmbH

Hietzinger Hauptstraße 37

Wien, 1130, Austria

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: {MM/YYYY}

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

This leaflet can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.

This information is intended for healthcare professionals only:

Safe handling recommendations

Azacitidine Mylan is a cytotoxic medicine and, as with other potentially toxic compounds, caution should be exercised when handling and preparing azacitidine suspensions. Procedures for the proper handling and disposal of anticancer medicinal products should be followed.

If reconstituted azacitidine comes into contact with the skin, the affected area should be washed immediately and thoroughly with soap and water. If contact occurs with mucous membranes, they should be thoroughly rinsed with water.

Incompatibilities

This medicinal product must not be mixed with other medicinal products except as mentioned below (see section “Reconstitution procedure”).

Reconstitution procedure

Azacitidine Mylan must be reconstituted with water for injections. The shelf life of the reconstituted medicinal product can be extended by reconstituting it with refrigerated water for injections (between 2 °C and 8 °C). Information on storage of the reconstituted medicinal product is provided below.

1. The following items should be assembled:

Vial(s) of azacitidine, vial(s) of water for injections, non-sterile surgical gloves, alcohol-impregnated wipes, 5 ml syringes with needles.

2. Draw up 4 ml of water for injections into the syringe, ensuring that any trapped air is purged from the syringe.
3. Insert the needle of the syringe containing 4 ml of water for injections through the rubber stopper of the azacitidine vial; then inject the water for injections into the vial.
4. After removing the syringe and needle, the vial should be shaken vigorously until a uniform cloudy suspension is obtained. After reconstitution, each ml of suspension contains 25 mg of azacitidine (100 mg/4 ml). The reconstituted product is a cloudy, homogeneous suspension without clumps. The suspension should be discarded if large particles or clumps are present. Do not filter the suspension after reconstitution, as this may remove the active ingredient. Note that some adapters, infusion needles, and closed systems contain filters; therefore, such systems should not be used for administration of the medicinal product after reconstitution.
5. Clean the rubber stopper and insert a new syringe with a needle into the vial. Invert the vial, ensuring that the tip of the needle is below the liquid level. Pull back the plunger to withdraw the required amount of medicinal product for the correct dose, ensuring that any trapped air in the syringe is purged. Then remove the syringe with needle from the vial and discard the needle.
6. Firmly attach a new subcutaneous injection needle (25 gauge is recommended) to the syringe. The needle should not be purged before injection to reduce the incidence of local reactions at the injection site.
7. When more than one vial is required, repeat all the above steps for the preparation of the suspension. For doses requiring more than one vial, the dose should be divided into equal parts; for example, a 150 mg dose = 6 ml; 2 syringes with 3 ml in each syringe. Due to retention in the vial and needle, it may not be possible to withdraw all the suspension from the vial.
8. The contents of the dosing syringe should be resuspended immediately before administration. The temperature of the suspension at the time of injection should be approximately 20 to 25 °C. To resuspend, roll the syringe vigorously between the palms of the hands until a uniform cloudy suspension is obtained. The suspension should be discarded if large particles or clumps are present.

Storage of the reconstituted medicinal product

For immediate use

The Azacitidine Mylan suspension may be prepared immediately before use and the reconstituted suspension should be administered within 1 hour. If more than 1 hour has elapsed, the reconstituted suspension must be properly discarded and a new dose prepared.

For later use

When reconstituted with non-refrigerated water for injections, the reconstituted suspension must be placed in a refrigerator (temperature between 2 °C and 8 °C) immediately after reconstitution and stored in the refrigerator for a maximum of 8 hours. If the time in the refrigerator exceeds 8 hours, the suspension must be properly discarded and a new dose prepared.

When 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 reconstitution and stored in the refrigerator for a maximum of 22 hours. If the time in the refrigerator exceeds 22 hours, the suspension must be properly discarded and a new dose prepared.

The filled syringe containing the reconstituted suspension should be allowed to reach a temperature of 20 to 25 °C for 30 minutes before administration. If more than 30 minutes have elapsed, the reconstituted suspension must be properly discarded and a new dose prepared.

Calculation of an individual dose

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 provided only as an example for calculating individual azacitidine doses, based on an average BSA of 1.8 m².

Route of administration

Reconstituted Azacitidina Mylan must be administered by subcutaneous injection (insert the needle at an angle of 45–90°) using a 25-gauge needle into the arm, thigh, or abdomen.

Doses exceeding 4 ml must be administered at two separate injection sites.

Injection sites should be rotated. New injections should be administered at least 2.5 cm away from the previous injection site and never into areas that are tender, bruised, red, or hardened.

Disposal

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.