VYXEOS LIPOSOMAL 44 mg/100 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Vyxeos liposomal 44 mg/100 mg powder for concentrate for solution for infusion

daunorubicin and cytarabine

Read all of this leaflet carefully before you start taking 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 or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Vyxeos liposomal is and what it is used for
2. What you need to know before you receive Vyxeos liposomal
3. How Vyxeos liposomal will be given to you
4. Possible side effects
5. Storage of Vyxeos liposomal
6. Contents of the pack and other information

1. What Vyxeos liposomal is and what it is used for

What Vyxeos liposomal is

Vyxeos liposomal belongs to a group of medicines called ‘antineoplastics’ used to treat cancer. It contains two active substances, called ‘daunorubicin’ and ‘cytarabine’, in the form of tiny particles known as ‘liposomes’. These active substances work in different ways to destroy cancer cells, preventing them from growing and dividing. Encapsulating them in liposomes prolongs their action in the body and helps them enter cancer cells and destroy them.

What Vyxeos liposomal is used for

Vyxeos liposomal is used to treat patients with newly diagnosed acute myeloid leukemia (a cancer of the white blood cells). It is given when the leukemia has been caused by previous treatments (known as treatment-related acute myeloid leukemia) or when there are certain changes in the bone marrow (known as acute myeloid leukemia with myelodysplasia-related changes).

2. What you need to know before you receive Vyxeos liposomal

Do not use Vyxeos liposomal

• if you are allergic to the active substances (daunorubicin or cytarabine) or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Your doctor will monitor you during treatment. Tell your doctor or nurse before starting Vyxeos liposomal:

• if you have low levels of platelets, red blood cells, or white blood cells in your blood (you will have a blood test before starting treatment). If this is the case:

• your doctor may give you a medicine to help you avoid infection;
• your doctor will also examine you for infections during treatment.

• if you have ever had a heart problem or heart attack, or have previously taken cancer medicines with ‘anthracyclines’. If this is the case, your doctor may examine your heart before starting and during treatment.
• if you think you may be pregnant. You must use an effective method of contraception to avoid becoming pregnant (you or your partner) during treatment and for 6 months after the last dose.

• if you have any allergic reaction (hypersensitivity). Your doctor may stop treatment temporarily or permanently, or reduce the infusion rate, if hypersensitivity occurs.

• if you have had liver or kidney problems. Your doctor will monitor you during treatment.

• if you have ever had a condition called Wilson's disease or another disorder related to copper metabolism, as Vyxeos liposomal contains a component called ‘copper gluconate’.

• if you are to be given a vaccine.

Your doctor will monitor your general health during treatment and may also give you other medicines to support your treatment, either before or with Vyxeos liposomal. If any of the above applies to you (or you are not sure), tell your doctor, pharmacist, or nurse before using Vyxeos liposomal.

Children and adolescents

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

Other medicines and Vyxeos liposomal

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. This is because Vyxeos liposomal may affect the way other medicines work. Also, some other medicines may affect the way Vyxeos liposomal works.

In particular, tell your doctor or nurse if you are taking any of the following medicines:

• cancer medicines that may affect the heart, such as doxorubicin;
• medicines that may affect the liver.

Pregnancy and breastfeeding

Do not use Vyxeos liposomal during pregnancy, as it may harm the baby. Use an effective method of contraception during treatment and for 6 months after the last dose. Tell your doctor immediately if you become pregnant during treatment.

Do not breastfeed during treatment with Vyxeos liposomal, as it may harm the baby.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor for advice before taking this medicine.

Contraception in men

Use an effective method of contraception during treatment with Vyxeos liposomal and for 6 months after treatment.

Driving and using machines

You may feel drowsy or dizzy after receiving Vyxeos liposomal. If this happens, do not drive or use machines or tools.

3. How Vyxeos liposomal will be given to you

Vyxeos liposomal should be given to you by a doctor or nurse with experience in treating acute myeloid leukemia.

• It is given as an infusion (drip) into a vein.
• The infusion is given over 1 hour and 30 minutes (90 minutes).

Your doctor or nurse will calculate the dose of the medicine based on your weight and height. Your treatment will be given in ‘cycles’. Each cycle is given as a separate infusion, and there may be weeks between each cycle.

You will receive a first cycle of treatment, and your doctor will decide if you will receive more cycles of treatment based on how you respond to treatment and any side effects you may experience. Your doctor will assess your response to treatment after each cycle.

• During your first cycle, you will receive an infusion on days 1, 3, and 5.
• In additional cycles, you will receive an infusion on days 1 and 3. This can be repeated as needed.

While you are receiving treatment with Vyxeos liposomal, your doctor will regularly take blood samples to check how you are responding to treatment and to ensure it is being well tolerated. Your doctor may also check your heart, as Vyxeos liposomal can affect it.

If you receive more Vyxeos liposomal than you should

This medicine will be given to you in a hospital, by a doctor or nurse. It is unlikely that you will be given too much; however, tell your doctor or nurse if you have any concerns.

If you miss a dose

Contact your doctor or nurse as soon as possible.

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

4. Possible side effects

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

Serious side effects that may affect more than 1 in 10 people (very common)Vyxeos liposomal may reduce the number of white blood cells that fight infection and blood cells that help your blood to clot (platelets), leading to bleeding disorders such as nosebleeds and bruising. Vyxeos liposomal may also cause heart problems and damage to the heart muscle.

Therefore, you must tell your doctor immediatelyif you:

• have a fever, chills, sore throat, cough, mouth ulcers, or any other signs of infection
• have bleeding or bruising without injury
• have chest pain or leg pain
• feel short of breath.

Tell your doctor immediately if you experience any of the above side effects.

Other side effects

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

• a decrease in the number of platelets (the cells that help the blood to clot) that can cause bruising or bleeding
• fever, often with other signs of infection, due to a very low number of white blood cells (febrile neutropenia)
• slow, fast, or irregular heartbeats, chest pain (which can be a sign of infection)
• vision problems, blurred vision
• pain or inflammation of the tissue that lines the digestive system (mucositis), or abdominal pain (stomach), constipation, decreased appetite, diarrhea, nausea (feeling sick) or vomiting
• redness of the skin, rash, muscle pain, headache, bone pain, joint pain, tiredness, generalized swelling, including swelling of arms and legs

• headache, dizziness, confusion, difficulty sleeping, anxiety
• kidney failure
• shortness of breath, cough, fluid in the lungs
• itching
• bleeding
• high blood pressure or low blood pressure
• chills, low body temperature or high body temperature
• increased sweating

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

• a decrease in the number of red blood cells (anemia) that can cause tiredness and weakness
• kidney failure and blood test abnormalities due to the massive death of cancer cells (tumor lysis syndrome)
• stomach cramps or excess gas
• excessive night sweats
• hair loss

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

• numbness and rash on hands and feet (palmar-plantar erythrodysesthesia syndrome).

Reporting of side effects

If you experience 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 via 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. Storage of Vyxeos liposomal

• 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 carton and vial after EXP. The expiry date refers to the last day of the month stated.
• Store in a refrigerator (2°C to 8°C).
• Keep the vial in the outer carton to protect it from light.
• Store upright.
• After reconstitution, the vials should be stored in a refrigerator (2°C to 8°C) for a maximum of 4 hours, upright.
• After dilution, the solution in infusion bags should be stored in a refrigerator (2°C to 8°C) for a maximum of 4 hours. The total storage time, both for the reconstituted vials and after dilution in infusion bags, should not exceed 4 hours. The 90-minute infusion time is in addition to the 4-hour storage time.
• Do not use this medicine if you notice the presence of particles in the diluted solution.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Vyxeos liposomal contains

• The active substances are daunorubicin and cytarabine. Each 50 ml vial contains 44 mg of daunorubicin and 100 mg of cytarabine.

• After reconstitution, the solution contains 2.2 mg/ml of daunorubicin and 5 mg/ml of cytarabine encapsulated in liposomes.
• The other ingredients are distearoyl phosphatidylcholine, distearoyl phosphatidylglycerol, cholesterol, copper gluconate, tromethamine, and sucrose.

Appearance and pack size

Vyxeos liposomal is a purple powder for concentrate for solution for infusion, packaged in a glass vial.

Each pack contains 1 vial, 2 vials, or 5 vials. Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Jazz Pharmaceuticals Ireland Ltd

5th Floor

Waterloo Exchange

Waterloo Road

Dublin

D04 E5W7

Ireland

Tel: +353 1 968 1631

Email: [email protected]

Date of last revision of this leaflet:04/2024.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicines.

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

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This information is intended only for healthcare professionals:

Vyxeos liposomal is a cytotoxic medicine. Special handling and disposal procedures should be followed. The medicine is for single use only. It does not contain preservatives. Unused portions should not be stored for later administration.

Preparation instructions

• Determine the dose and number of Vyxeos liposomal vials based on the patient's individual body surface area as indicated in section 4.2.
• Remove the required number of Vyxeos liposomal vials from the refrigerator and let them reach room temperature (15°C to 30°C) for 30 minutes.
• Then, reconstitute each vial with 19 ml of sterile water for injection using a 20 ml syringe, and immediately start a 5-minute timer.
• Gently rotate the vial contents for 5 minutes, while gently inverting the vial every 30 seconds.
• Do not heat, shake vigorously, or agitate.
• After reconstitution, let it stand for 15 minutes.
• The reconstituted product will be a homogeneous, opaque, purple dispersion, essentially free of visible particles.

• If the reconstituted medicine is not diluted immediately in an infusion bag, store in a refrigerator (2°C to 8°C) for a maximum of 4 hours.
• After storage of the reconstituted medicine in the vial for a maximum of 4 hours between 2°C and 8°C, the reconstituted medicine should be diluted immediately in an infusion solution and administered over a 90-minute infusion period.

• The reconstituted medicine in the vial and the reconstituted medicine diluted in an infusion solution are stable for 4 hours if stored at a temperature between 2°C and 8°C. The 4-hour stability period of the reconstituted medicine in the vial does not allow for any additional 4-hour stability period after dilution of the relevant dose from the reconstituted vial in the infusion solution.

The 4-hour stability period when the reconstituted medicine diluted in the infusion bag is stored at 2°C to 8°C does not include the time required for reconstitution or the 90-minute infusion time.

The diluted infusion solution should be infused immediately over the 90-minute infusion period after the up to 4-hour stability period.

• Calculate the required volume of reconstituted Vyxeos liposomal using the following formula:

[required volume (ml) = daunorubicin dose (mg/m²) x patient's body surface area (m²)/2.2 (mg/ml)]. The concentration of the reconstituted solution is 44 mg/20 ml (2.2 mg/ml) of daunorubicin and 100 mg/20 ml (5 mg/ml) of cytarabine.

• Gently invert each vial 5 times before withdrawing the concentrate for dilution.
• Withdraw the calculated volume of reconstituted Vyxeos liposomal from the vial or vials using a sterile syringe and transfer it to an infusion bag containing 500 ml of 9 mg/ml (0.9%) sodium chloride for injection or 5% glucose.

There may be residual medicine in the vial. Discard the unused portion.

• Gently invert the infusion bag to mix the solution. The diluted medicine gives a homogeneous, translucent dispersion with a dark purple color.
• If the diluted infusion solution is not used immediately, store in a refrigerator (2°C to 8°C) for a maximum of 4 hours.
• Gently invert the infusion bag to mix the solution after refrigeration.

Administration instructions

• Vyxeos liposomal should not be mixed or administered as an infusion with other medicines.
• Administer Vyxeos liposomal by intravenous infusion over 90 minutes using an infusion pump through a central venous catheter or a peripheral central catheter. An in-line filter with a minimum pore size of 15 µm can be used for intravenous infusion of Vyxeos liposomal.
• Flush the line after administration with 9 mg/ml (0.9%) sodium chloride for injection.

Disposal

This medicine may pose a potential risk to the environment due to its cytotoxic and antimitotic activities, which may induce potential effects on reproduction. All materials used for dilution and administration should be disposed of according to local procedures for the disposal of antineoplastics. Disposal of unused medicine and all materials that have come into contact with it should be done according to local regulations for cytotoxics.