Etraga

Package Leaflet: Information for the User

Etraga, 25 mg/mL, Powder for Suspension for Injection

Azacitidine

Read All of This Leaflet Carefully Before You Start Using This Medicine Because It Contains Important Information for You.

Keep This Leaflet. You May Need to Read It Again. If You Have Any Further Questions, Ask Your Doctor, Pharmacist, or Nurse. If You Get Any Side Effects, Talk to Your Doctor, Pharmacist, or Nurse. This Includes Any Possible Side Effects Not Listed in This Leaflet. See Section 4.

Contents of the Pack and Other Information

• 1. What Etraga Is and What It Is Used For
• 2. What You Need to Know Before You Use Etraga
• 3. How to Use Etraga
• 4. Possible Side Effects
• 5. How to Store Etraga
• 6. Contents of the Pack and Other Information

1. What Etraga Is and What It Is Used For

What Etraga Is

Etraga is an anti-cancer medicine belonging to a group of medicines called 'antimetabolites'. Etraga contains the active substance azacitidine.

What Etraga Is Used For

Etraga is used in adults who are not eligible for stem cell transplantation 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 with normal blood cell production.

How Etraga Works

Etraga 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 thought that its action involves changing the way genes are activated and deactivated, as well as disrupting the production of RNA and DNA. It is believed that these actions repair the disturbances in the maturation and growth of young blood cells in the bone marrow that cause myelodysplastic disorders and that they kill cancer cells in leukaemia. If you have any questions about how Etraga works or why it has been prescribed for you, ask your doctor or nurse.

2. What You Need to Know Before You Use Etraga

When You Should Not Use Etraga

• if you are allergic (hypersensitive) 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

Before starting treatment with Etraga, discuss this with your doctor, pharmacist, or nurse if you:

• have a low platelet count, red or white blood cell count,
• have kidney disease,
• have liver disease,
• have had heart disease, heart attack, or any lung disease in the past.

Etraga may cause a severe immune reaction called 'differentiation syndrome' (see section 4). Blood Tests Before starting treatment with Etraga and at the start of each treatment cycle, blood tests will be done. The purpose of these tests is to check that you have a sufficient number of blood cells and that your liver and kidneys are working properly.

Children and Adolescents

Etraga is not recommended for use in children and adolescents under 18 years of age.

Etraga and Other Medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Etraga may affect the way some other medicines work. Some other medicines may also affect the way Etraga works.

Pregnancy, Breastfeeding, and Fertility

Pregnancy You should not use Etraga if you are pregnant, as it may harm your baby. Women who could become pregnant should use effective contraception while using Etraga and for 6 months after stopping treatment with Etraga. If you become pregnant while using Etraga, tell your doctor immediately. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor or pharmacist for advice before using this medicine. Breastfeeding You should not breastfeed while using Etraga, as it is not known whether this medicine passes into human milk. Fertility Men should not father a child while using Etraga. Men should use effective contraception while using Etraga and for 3 months after stopping treatment with Etraga. You should consult your doctor if you wish to preserve sperm before starting this treatment.

Driving and Using Machines

If you experience side effects such as tiredness, do not drive, use tools, or operate machinery.

3. How to Use Etraga

Before administering Etraga to you, your doctor will give you another medicine to prevent nausea and vomiting at the start of each treatment cycle.

• The recommended dose of Etraga is 75 mg per square metre of body surface area. Your doctor will choose the right dose of Etraga for you, depending on your overall health, height, and weight. Your doctor will check your progress and may change your dose if necessary.
• Etraga is given every day for 1 week, followed by a 3-week rest period. This 'treatment cycle' is repeated every 4 weeks. You will usually receive at least 6 treatment cycles.

Etraga is given as an injection under the skin by a doctor or nurse. It can be injected under the skin of the thigh, abdomen, or arm. If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Side Effects

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

Seek Medical Attention Immediately if You Notice Any of the Following Serious Side Effects:

• Drowsiness, tremors, jaundice, abdominal distension, and bruising.These may be signs of life-threatening liver failure.
• Swelling of the feet and ankles, back pain, decreased urine output, increased thirst, rapid heartbeat, dizziness, nausea, vomiting, or loss of appetite, and feeling disoriented, anxious, or tired.These may be signs of life-threatening kidney failure.
• Fever. This may be due to infection caused by a low white blood cell count, which can be life-threatening.
• Chest pain or difficulty breathing, which may be accompanied by fever.This may be due to a life-threatening lung infection called 'pneumonia'.
• Bleeding, such as blood in the stool due to bleeding in the stomach or intestine, or bleeding in the head. These may be signs of a low platelet count.
• Difficulty breathing, swelling of the lips, itching, or rash.This may be due to an allergic reaction (hypersensitivity).

Other side effects include:

Very Common Side Effects(may affect more than 1 in 10 people)

• Decreased red blood cell count (anaemia). You may feel tired and pale.
• Decreased white blood cell count. This may be accompanied by fever. You are also more prone to infections.
• Low platelet count (thrombocytopenia). You may bruise or bleed easily.

Constipation, diarrhoea, nausea, vomiting.

• Lung infection.
• Chest pain, difficulty breathing.
• Tiredness.
• Injection site reaction, including redness, pain, or skin rash.
• Loss of appetite.
• Joint pain.
• Bruising.
• Rash.
• Red or purple spots under the skin.
• Abdominal pain.
• Itching.
• Fever.
• Nose and throat pain.
• Dizziness.
• Headache.
• Difficulty sleeping (insomnia).
• Nosebleeds.
• Muscle pain.
• Weakness (asthenia).
• Weight loss.
• Low potassium levels in the blood.

Common Side Effects(may affect up to 1 in 10 people)

• Bleeding in the brain.
• Blood infection caused by bacteria (sepsis). This may be due to a low white blood cell count.
• Bone marrow failure. This can lead to low red and white blood cell and platelet counts.
• A type of anaemia where the number of red and white blood cells and platelets is reduced.
• Urinary tract infection.
• Viral infection causing cold sores.
• Bleeding gums, stomach or intestinal bleeding, bleeding from the anus due to haemorrhoids (haemorrhoidal bleeding), eye bleeding, bleeding under the skin or in the skin (bruising).
• Blood in the urine.
• Mouth or tongue ulcers.
• Skin changes at the injection site, including swelling, hard lumps, bruising, bleeding in the skin (bruising), rash, itching, and skin colour changes.
• Redness of the skin.
• Skin infection (cellulitis).
• Nose and throat infection or sore throat.
• Nose or sinus pain (sinusitis).
• High or low blood pressure (hypertension or hypotension).
• Difficulty breathing when moving around.
• Throat and larynx pain.
• Nausea.
• Weakness.
• General feeling of being unwell.
• Anxiety.
• Disorientation.
• Hair loss.
• Kidney failure.
• Dehydration.
• White patches on the tongue, inside the cheeks, and sometimes on the palate, gums, and tonsils (oral thrush).
• Fainting.
• Drop in blood pressure when standing up (orthostatic hypotension), leading to dizziness when changing position to standing or sitting.
• Drowsiness.
• Bleeding at the catheter site.
• A disease of the intestines that can cause fever, vomiting, and abdominal pain (diverticulitis).
• Fluid around the lungs (pleural effusion).
• Chills.
• Muscle spasms.
• A raised, itchy rash on the skin (hives).
• Fluid around the heart (pericardial effusion).

Uncommon Side Effects(may affect up to 1 in 100 people)

• Allergic reaction (hypersensitivity).
• Tremors.
• Liver failure.
• Large, purple, raised, painful spots on the skin, with fever.
• Painful skin ulcers (necrotising fasciitis).
• Inflammation of the sac surrounding the heart (pericarditis).

Rare Side Effects(may affect up to 1 in 1,000 people)

• Dry cough.
• Painful swelling of the tips of the fingers (digital clubbing).
• Tumour lysis syndrome - a complication of cancer treatment that can cause changes in blood chemistry; high levels of potassium, phosphorus, uric acid, and low calcium levels, leading to kidney problems, irregular heartbeat, seizures, and sometimes death.

Frequency Not Known(frequency cannot be estimated from the available data)

• A skin infection that spreads quickly, causing tissue damage that can be life-threatening (necrotising fasciitis).
• A severe immune reaction (differentiation syndrome) that can cause fever, cough, difficulty breathing, rash, decreased urine output, low blood pressure (hypotension), swelling of the hands or feet, and sudden weight gain.
• Inflammation of the blood vessels in the skin, which 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 Possible Side Effects Not Listed in This Leaflet. You Can Also Report Side Effects Directly to the Medicines and Healthcare Products Regulatory Agency (MHRA) Using the Yellow Card Scheme. The Yellow Card Scheme Can Be Found at https://www.mhra.gov.uk/yellowcard. By Reporting Side Effects, You Can Help Provide More Information on the Safety of This Medicine.

5. How to Store Etraga

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 and Carton After 'EXP'. The Expiry Date Refers to the Last Day of That Month. Your Doctor, Pharmacist, or Nurse Are Responsible for Storing Etraga. They Are Also Responsible for Preparing Etraga and Disposing of Any Unused Medicine. Unopened Vials - No Special Storage Conditions. After Preparation:

For Azacitidine Prepared with Unrefrigerated Water for Injection, Chemical and Physical Stability Has Been Demonstrated for 45 Minutes at 25°C and for 8 Hours at 2°C-8°C. The Shelf-Life of the Prepared Medicinal Product Can Be Extended by Preparing It with Refrigerated (2°C-8°C) Water for Injection. For Azacitidine Prepared with Refrigerated (2°C-8°C) Water for Injection, Chemical and Physical Stability Has Been Demonstrated for 32 Hours at 2°C-8°C. For Microbiological Reasons, the Prepared Product Should Be Used Immediately. If Not Used Immediately, the User Is Responsible for the Storage Conditions Prior to Administration. However, It Must Not Be Stored for More Than 8 Hours at 2°C-8°C for the Product Prepared with Unrefrigerated Water for Injection, or More Than 32 Hours for the Product Prepared with Refrigerated (2°C-8°C) Water for Injection. Allow the Suspension to Reach Room Temperature (20°C-25°C) for No More Than 30 Minutes Before Administration. If More Than 30 Minutes Have Passed, the Suspension Should Be Discarded and a New Dose Prepared.

6. Contents of the Pack and Other Information

What Etraga Contains

The Active Substance Is Azacitidine. One Vial Contains 100 Mg or 150 Mg of Azacitidine. After Reconstitution with Water for Injection, the Suspension Contains 25 Mg/mL of Azacitidine. The Other Ingredient Is Mannitol.

What Etraga Looks Like and Contents of the Pack

Etraga Is a White Powder for Suspension for Injection and Is Supplied in a Glass Vial with a Bromobutyl Rubber Stopper and a White (for 100 Mg Vial) or Orange (for 150 Mg Vial) Plastic Flip-Off Cap in a Carton. Pack Size: 1 Vial - 150 Mg

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

STADA Arzneimittel AG Stadatrasse 2-18 61118 Bad Vilbel Germany

Manufacturer:

AqVida GmbH Kaiser-Wilhelm-Str. 89 20355 Hamburg Germany STADA Arzneimittel AG Stadastrasse 2-18 61118 Bad Vilbel Germany For Further Information, Please Contact the Marketing Authorisation Holder: Stada Pharm Sp. z o.o. ul. Krakowiaków 44 02-255 Warszawa Tel. +48 22 737 79 20

This Medicinal Product Is Authorised in the Member States of the European Economic Area Under the Following Names:

Iceland Etraga 25 Mg/mL Powder for Suspension for Injection Denmark Etraga Sweden Etraga 25 Mg/mL Powder for Injection Suspension Finland Etraga 25 Mg/mL Powder for Suspension for Injection Norway Etraga 25 Mg/mL Powder for Injection Suspension Croatia Etraga Hungary Etraga Poland Etraga Romania Etraga Czech Republic Etraga

Date of Last Revision of the Leaflet:

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Information Intended for Healthcare Professionals Only:

Handling Precautions Etraga Is a Cytotoxic Medicinal Product, and as with Other Potentially Toxic Compounds, Caution Should Be Exercised in the Handling and Preparation of the Azacitidine Suspension. Procedures for Proper Handling and Disposal of Anti-Cancer Medicinal Products Should Be Followed. In the Event of Skin Contact with the Reconstituted Azacitidine, the Area Should Be Thoroughly Washed with Soap and Water. In the Event of Contact with Mucous Membranes, They Should Be Flushed with Water. Female Healthcare Workers Who Are Pregnant Should Not Handle or Administer This Medicinal Product. Incompatibilities the Medicinal Product Should Not Be Mixed with Other Medicinal Products Except Those Mentioned Below (See 'Preparation Procedure'). Preparation Procedure the Etraga Product Should Be Reconstituted with Water for Injection. The Shelf-Life of the Reconstituted Medicinal Product Can Be Extended by Reconstituting the Product with Refrigerated (2°C-8°C) Water for Injection. Details of Storage of the Reconstituted Product Are Given Below.

• 1. You Will Need the Following: Vial(s) of Azacitidine, Vial(s) of Water for Injection, Non-Sterile Surgical Gloves, Alcohol Swabs, Syringe(s) for Injection with Needle(s).
• 2. Draw the Appropriate Amount of Water for Injection (See Table Below) into a Syringe and Ensure That the Air Has Been Removed from the Syringe.

• 3. Insert the Needle of the Syringe Containing Water for Injection Through the Rubber Stopper of the Vial of Azacitidine and Then Inject the Water for Injection into the Vial.
• 4. After Removing the Syringe and Needle, Vigorously Shake the Vial Until a Uniform, Turbid Suspension Is Obtained. After Reconstitution, Each Ml of the Suspension Contains 25 Mg of Azacitidine (100 Mg/4 Ml or 150 Mg/6 Ml). the Reconstituted Product Is a Uniform, Turbid Suspension Without Aggregates. Discard the Suspension If It Contains Large Particles or Aggregates. Do Not Filter the Suspension After Reconstitution, as This May Remove the Active Substance. Note That Some Adapters, Needles, and Closed Systems Contain Filters. Such Devices Should Not Be Used for Administration of the Medicinal Product After Reconstitution.
• 5. Clean the Rubber Stopper with an Alcohol Swab and Insert a New Syringe with a Needle into the Vial. Then Invert the Vial and Ensure That the Needle Tip Is Below the Level of the Liquid. Draw the Required Volume of the Medicinal Product into the Syringe to Obtain the Appropriate Dose. Ensure That the Air Has Been Removed from the Syringe. Then Withdraw the Needle from the Vial and Discard the Needle.
• 6. Attach a New Injection Needle (25G Recommended) to the Syringe. Do Not Flush the Needle Before Injection to Reduce the Frequency of Local Reactions at the Injection Site.
• 7. For a Dose of 150 Mg = 6 Ml, Use the 150 Mg Vial. Due to the Overfill of the Vial and the Needle, It May Not Be Possible to Withdraw the Entire Suspension from the Vial.
• 8. the Contents of the Syringe Must Be Resuspended Immediately Before Administration. the Temperature of the Suspension at the Time of Injection Should Be Around 20°C-25°C. to Resuspend, Vigorously Rotate the Syringe Between the Palms Until a Uniform, Turbid Suspension Is Obtained. Discard the Suspension If It Contains Large Particles or Aggregates.

After Preparation: For Azacitidine Prepared with Unrefrigerated Water for Injection, Chemical and Physical Stability Has Been Demonstrated for 45 Minutes at 25°C and for 8 Hours at 2°C-8°C. the Shelf-Life of the Prepared Medicinal Product Can Be Extended by Preparing It with Refrigerated (2°C-8°C) Water for Injection. for Azacitidine Prepared with Refrigerated (2°C-8°C) Water for Injection, Chemical and Physical Stability Has Been Demonstrated for 32 Hours at 2°C-8°C. for Microbiological Reasons, the Prepared Product Should Be Used Immediately. If Not Used Immediately, the User Is Responsible for the Storage Conditions Prior to Administration. However, It Must Not Be Stored for More Than 8 Hours at 2°C-8°C for the Product Prepared with Unrefrigerated Water for Injection, or More Than 32 Hours for the Product Prepared with Refrigerated (2°C-8°C) Water for Injection. Allow the Suspension to Reach Room Temperature (20°C-25°C) for No More Than 30 Minutes Before Administration. If More Than 30 Minutes Have Passed, the Suspension Should Be Discarded and a New Dose Prepared. Dose Calculation the Total Dose Can Be Calculated Based on Body Surface Area (BSA) as Follows: Total Dose (Mg) = Dose (Mg/M2) x BSA (M2) the Following Table Is an Example of How to Calculate Individual Doses of Azacitidine Based on an Average BSA of 1.8 M2.

Administration After Reconstitution, the Suspension Should Not Be Filtered. the Reconstituted Etraga Product Should Be Administered by Subcutaneous Injection Using a 25G Needle (Insert the Needle at an Angle of 45-90°) into the Arm, Thigh, or Abdomen.

Doses Above 4 Ml Should Be Divided Equally and Administered at Two Different Sites.

Rotate Injection Sites. New Injections Should Be Given at Least 2.5 Cm from the Previous Injection Site and Never into Areas That Are Tender, Bruised, Red, or Hard. Any Unused Medicinal Product or Waste Material Should Be Disposed of in Accordance with Local Requirements.