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

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

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

daunorubicin and cytarabine

Read the entire leaflet carefully before starting to take 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, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Vyxeos liposomal is and what it is used for
2. What you need to know before receiving Vyxeos liposomal
3. How you will receive Vyxeos liposomal
4. Possible adverse effects
5. How to store 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 "antineoplastic agents", used to treat cancer. It contains two active substances, known as "daunorubicin" and "cytarabine", in the form of tiny particles called "liposomes". These active substances work in different ways to destroy cancer cells by preventing them from growing and dividing. Packaging them into liposomes prolongs their action in the body and helps them enter cancer cells to 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 start receiving 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. Talk to your doctor or nurse before starting to receive 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 prevent infection;

• your doctor will also check you for infections during treatment.

• if you have ever had a heart problem or heart attack, or previously received anticancer medicines containing “anthracyclines.” If this is the case, your doctor may examine your heart before and during treatment.

• if you think you may be pregnant. You must use an effective method of contraception to prevent pregnancy (you or your partner) during treatment and for six months after the last dose.

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

• if you have 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 due to receive a vaccine.

Your doctor will monitor your overall health during treatment and may also give you other medicines to support your treatment, either before or together with Vyxeos liposomal. If any of the above situations apply to you (or you are unsure), inform your doctor, pharmacist, or nurse before using Vyxeos liposomal.

Children and adolescents

The use of Vyxeos liposomal is not recommended 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 need to take any other medicines. This is because Vyxeos liposomal may affect how other medicines work. In addition, some other medicines may affect how Vyxeos liposomal works.

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

• anticancer 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 unborn child. Use an effective method of contraception during treatment and for six months after the last dose. Inform your doctor immediately if you become pregnant during treatment.

Do not breastfeed during treatment with Vyxeos liposomal, as it may be harmful to the breastfed infant.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using 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 operate machinery or tools.

3. How you will receive Vyxeos liposomal

Vyxeos liposomal must be administered by a physician or nurse experienced in the treatment of AML.

• It is given as an intravenous infusion (a drip into a vein).
• The infusion is administered over one and a half hours (90 minutes).

Your physician or nurse will calculate the dose of the medicine based on your body surface area. Your treatment will be given in "cycles." Each cycle consists of separate infusions, and there may be several weeks between cycles.

You will receive an initial treatment cycle, and your physician will decide whether additional treatment cycles are needed based on your response to treatment and any side effects you may experience. Your physician will evaluate your response to treatment after each cycle.

• During your first cycle, you will receive an infusion on days 1, 3, and 5.
• In subsequent cycles, you will receive an infusion on days 1 and 3. This may be repeated if necessary.

While you are receiving treatment with Vyxeos liposomal, your physician will perform regular blood tests to assess your response to treatment and to monitor for tolerability. Your physician may also monitor your heart, as Vyxeos liposomal can affect heart function.

If you are given more Vyxeos liposomal than you should

This medicine will be administered to you in a hospital setting by a physician or nurse. It is unlikely that you will receive an overdose; however, if you have any concerns, inform your physician or nurse immediately.

If you miss an appointment

Contact your physician or nurse as soon as possible.

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

4. Possible adverse effects

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

Serious adverse effects that may affect more than 1 in 10 people (very common): Vyxeos liposomal may reduce the number of white blood cells, which fight infections, and also reduce blood cells that help with clotting (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 inform your doctor immediately if you experience:

• fever, chills, sore throat, cough, mouth ulcers, or any other sign of infection
• bleeding or bruising without injury
• chest pain or leg pain
• shortness of breath.

Inform your doctor immediately if you experience any of the adverse effects listed above.

Other adverse effects

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

• a decrease in the number of platelets (cells that help blood to clot), which may cause bruising or bleeding
• fever, often with other signs of infection, due to very low levels of white blood cells (febrile neutropenia)
• slow, fast, or irregular heartbeat, chest pain (which may be a sign of infection)
• visual disturbances, blurred vision
• pain or inflammation of the tissue lining the inside of the digestive system (mucositis), or abdominal (stomach) pain, constipation, decreased appetite, diarrhea, nausea (feeling sick) or vomiting
• skin redness, rashes, muscle pain, headache, bone pain, joint pain, fatigue, general 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
• increased or decreased blood pressure
• chills, low body temperature or high body temperature
• increased sweating

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

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

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

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the carton and vial after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (2 °C to 8 °C).
• Keep the vial in the outer packaging to protect it from light.
• Store in an upright position.
• After reconstitution, vials should be stored in a refrigerator (2 °C to 8 °C) for a maximum of 4 hours, in an upright position.
• 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, including both reconstituted vials and diluted solution in infusion bags, must not exceed 4 hours. The 90-minute infusion time is included within these 4 hours of storage.
• Do not use this medicine if you notice the presence of particles in the diluted solution.
• Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Pack contents and other information

Composition of Vyxeos liposomal

• 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 components are distearoyl phosphatidylcholine, distearoyl phosphatidylglycerol, cholesterol, copper gluconate, tromethamine, and sucrose.

Nature of the product and pack contents

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

Each pack contains 1, 2, or 5 vials. Only certain pack sizes may be marketed.

Marketing Authorization 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 the most recent revision of this summary: 04/2024.

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

This summary 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:

Vyxeos liposomal is a cytotoxic medicine. Special procedures must be followed for handling and disposal. The medicine is for single use only. It contains no preservatives. Unused residues must not be stored for later administration.

Preparation instructions

• Determine the dose and number of Vyxeos liposomal vials based on the individual patient's body surface area as indicated in section 4.2.

• Remove the required number of Vyxeos liposomal vials from the refrigerator and allow them to reach room temperature (15 °C to 30 °C) for 30 minutes.

• Reconstitute each vial with 19 ml of sterile water for injections using a 20 ml syringe, and immediately start a 5-minute timer.

• Gently rotate the vial contents for 5 minutes, inverting the vial gently every 30 seconds.

• Do not heat, swirl, or shake vigorously.

• After reconstitution, allow the solution to 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 into an infusion bag, store it in the refrigerator (2 °C to 8 °C) for up to 4 hours.

• After storage of the reconstituted medicine in the vial for up to 4 hours at 2 °C to 8 °C, the reconstituted medicine must be diluted immediately into 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 when stored at 2 °C to 8 °C. The 4-hour stability period for the reconstituted medicine in the vial does not allow for an additional 4-hour stability period after dilution of the appropriate dose from the reconstituted vial into the infusion solution.

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

o The diluted infusion solution must be infused immediately over the 90-minute infusion period following 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 five times before withdrawing the concentrate for dilution.
• Aseptically withdraw the calculated volume of reconstituted Vyxeos liposomal from the vial(s) using a sterile syringe, and transfer it to an infusion bag containing 500 ml of 9 mg/ml (0.9%) sodium chloride solution for injection or 5% glucose solution.

Residual medicine may remain in the vial. Discard any unused portion.

• Gently invert the infusion bag to mix the solution. Dilution of the reconstituted medicine results in a homogeneous, translucent, dark purple dispersion.
• If the diluted infusion solution is not used immediately, store it in the refrigerator (2 °C to 8 °C) for up to 4 hours.
• Gently invert the infusion bag to mix the solution after refrigeration.

Administration instructions

• Vyxeos liposomal must not be mixed or administered as an infusion with other medicines.
• Administer Vyxeos liposomal as a continuous intravenous infusion over 90 minutes using an infusion pump via a central venous catheter or a peripherally inserted central catheter (PICC). An in-line membrane filter may be used for intravenous infusion of Vyxeos liposomal, provided the minimum pore diameter of the filter is ≥15 µm.
• Flush the line after administration with 9 mg/ml (0.9%) sodium chloride solution for injection.

Disposal

This medicine may pose a potential risk to the environment due to its cytotoxic and antimitotic activities, which could induce possible reproductive effects. All materials used for dilution and administration must be disposed of in accordance with local procedures for the disposal of antineoplastic agents. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations for cytotoxic medicines.