Label: Information for the Patient

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

daunorubicina and citarabina

Read the entire label carefully before starting to take this medication, because it contains important information for you.

• Keep this label, 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 not listed in this label. See section 4.

What is Vyxeos liposomal

Vyxeos liposomal belongs to a group of medications called «antineoplastic», used for cancer treatment. It contains two active principles, called «daunorubicina» and «citarabina», in the form of minuscule particles known as «liposomes». These active principles act in different ways to destroy cancer cells, preventing them from growing and dividing. Packaging them in liposomes prolongs their action in the body, and helps them to enter cancer cells and destroy them.

What is Vyxeos liposomal used for

Vyxeos liposomal is used for the treatment of patients with acute myeloid leukemia of recent diagnosis (a cancer of white blood cells). It is administered when 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 «changes related to myelodysplasia»).

Do not use Vyxeos liposomal

• if you are allergic to the active ingredients (daunorubicin or citarabine) or to any of the other components of this medication (listed in section 6).

Warnings and precautions

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

• if you have low platelet, red blood cell, or white blood cell counts in your blood (a blood test will be done before starting treatment). If this is your case:

• if you have ever had a heart problem or a heart attack, or if you have previously taken cancer medications with «antracyclines». If this is your case, your doctor may examine your heart before starting and during treatment.
• if you think you may be pregnant. You must use an effective contraceptive method to avoid becoming pregnant (you or your partner) during treatment and the six months after the last dose.

• if you have any allergic reaction (hypersensitivity). Your doctor may temporarily or permanently suspend treatment, or decrease 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, since Vyxeos liposomal contains a component called «copper gluconate».

• if you are to receive a vaccine.

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

Children and adolescents

Use of Vyxeos liposomal is not recommended in children and adolescents under 18 years old.

Other medications and Vyxeos liposomal

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication. This is because Vyxeos liposomal may affect how other medications work. Additionally, some other medications may affect how Vyxeos liposomal works.

Particularly, inform your doctor or nurse if you are taking any of the following medications:

• chemotherapy medications that can affect the heart, such as doxorubicin;
• medications that can affect the liver.

Pregnancy and breastfeeding

You must not use Vyxeos liposomal during pregnancy, as it may be harmful to the child. Use an effective contraceptive method during treatment and for the six months after the last dose. Inform your doctor immediately if you become pregnant during treatment.

You must not breastfeed during treatment with Vyxeos liposomal, as it may be harmful to the child.

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

Contraception in men

Use an effective contraceptive method during treatment with Vyxeos liposomal and for the 6 months after.

Driving and operating machinery

You may feel drowsiness or dizziness after receiving Vyxeos liposomal. If this happens, do not drive or operate machinery.

Vyxeos liposomal must be administered by a doctor or experienced nurse who specializes in the treatment of LMA.

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

Your doctor or nurse will calculate the dosage of the medication based on your weight and height. Your treatment will be administered in "cycles." Each cycle is administered as a separate infusion, and there may be weeks between cycles.

You will receive an initial cycle of treatment, and your doctor will decide if additional treatment cycles are necessary based on your response to the treatment and any side effects you may experience. Your doctor will evaluate your response to the treatment after each cycle.

• During your initial 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 may be repeated as necessary.

While receiving treatment with Vyxeos liposomal, your doctor will perform regular blood tests to evaluate your response to the treatment and to ensure it is well tolerated. Your doctor may also monitor your heart, as Vyxeos liposomal may affect it.

If You Receive More Vyxeos Liposomal Than You Should

This medication will be administered in a hospital by a doctor or nurse. It is unlikely that you will receive too much; however, inform your doctor or nurse if you have any doubts.

If You Miss an Appointment

Notify your doctor or nurse as soon as possible.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Severe side 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 the 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 immediatelyif you experience:

• fever, chills, sore throat, cough, mouth ulcers, or any other symptom 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 side effects listed above.

Other side effects

Side effectsvery common(may affect more than 1 in 10 people):

• a decrease in the number of platelets (the cells that help blood to clot) that may cause bruising or bleeding
• fever, often with other signs of infection, due to a very low number of white blood cells (febrile neutropenia)
• slow, rapid, or irregular heartbeats, chest pain (which may be a sign of infection)
• visual problems, blurred vision
• abdominal pain (stomach), diarrhea, nausea (urge to vomit), or vomiting
• skin redness, rashes, muscle pain, headache, bone pain, joint pain, fatigue, generalized inflammation, including swelling of arms and legs

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

Side effectscommon(may affect up to 1 in 10 people):

• a decrease in the number of red blood cells (anemia) causing fatigue and weakness
• renal insufficiency and abnormalities in blood tests due to massive cell death (tumor lysis syndrome)
• stomach cramps or excessive gas
• excessive nocturnal sweating
• hair loss

Side effectsuncommon(may affect up to 1 in 100 people):

• numbness and rash on hands and feet (erythromelalgia palmo-plantar syndrome).

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly throughthe national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and vial after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (2°C to 8°C).
• Keep the vial in the outer packaging to protect it from light.
• Store in upright position.
• After reconstitution, the vials should be stored in refrigerator (2°C to 8°C) for a maximum of 4 hours, in upright position.
• After dilution, the solution in infusion bags should be stored in refrigerator (2°C to 8°C), for a maximum of4 hours. The total conservation time, both for reconstituted vials and after dilution in infusion bags, should not exceed 4 hours. The 90-minute infusion time is added to the 4 hours of conservation.
• Do not use this medication if you observe the presence of particles in the diluted solution.
• Medicines should not be disposed of through drains. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Vyxeos liposomal

• The active ingredients are daunorubicina and citarabina. Each vial of 50 ml contains 44 mg of daunorubicina and 100 mg of citarabina.

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

Appearance of the product and contents of the pack

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

Each pack contains 1 vial, 2 vials, or 5 vials. Some pack sizes may only be marketed.

Marketing authorization holder and manufacturer responsible

Jazz Pharmaceuticals Ireland Ltd

5th Floor

Waterloo Exchange

Waterloo Road

Dublin

D04 E5W7

Ireland

Phone:+35319681631

Email: [email protected]

Last review date of this leaflet:04/2024.

Other sources of information

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

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

--------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Vyxeos liposomal is a cytotoxic medicinal product. Special handling and disposal procedures must be followed. The medicinal product 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 the number of vials of Vyxeos liposomal according to the individual patient's body surface area as indicated in section 4.2.
• Remove the required number of vials of Vyxeos liposomal from the refrigerator, and wait for 30 minutes for it to reach room temperature (15°C to 30°C).
• Then, 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 contents of the vial for 5 minutes, while inverting the vial gently every 30 seconds.
• Do not heat, agitate, or shake vigorously.
• After reconstitution, let it stand for 15 minutes.
• The reconstituted product will be an opaque and homogeneous, purple, basically particle-free dispersion.

• If the reconstituted medicinal product does not immediately dilute in an infusion bag, store in the refrigerator (2°C to 8°C) for a maximum of 4 hours.
• After storing the reconstituted medicinal product in the vial for a maximum of 4 hours between 2°C and 8°C, the reconstituted medicinal product must immediately dilute in an infusion solution and administer over a 90-minute infusion period.

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

orThe 4-hour stability period when the reconstituted medicinal product diluted in the infusion bag is stored at a temperature between 2°C and 8°C does not include the time required for reconstitution or the 90-minute infusion time.

orThe diluted infusion solution must be infused immediately over the 90-minute infusion period after the 4-hour stability period.

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

[required volume (ml) = daunorubicina dose (mg/m²) x SC of the patient (m²)/2.2 (mg/ml)]. The concentration of the reconstituted solution is 44 mg/20 ml (2.2 mg/ml) of daunorubicina and 100 mg/20 ml (5 mg/ml) of citarabina.

• Invert the vial gently 5 times before removing the concentrate for dilution.
• Remove the calculated volume of reconstituted Vyxeos liposomal from the vial or vials using a sterile syringe, and transfer it to an infusion bag with 500 ml of 9 mg/ml (0.9%) sodium chloride solution for injections, or 5% glucose solution.

There may be residual medicinal product in the vial. Dispose of the unused portion.

• Invert the infusion bag gently to mix the solution. The dilution of the reconstituted medicinal product results in a homogeneous and translucent, dark purple dispersion.
• If the diluted infusion solution is not used immediately, store in the refrigerator (2°C to 8°C) for a maximum of 4 hours.
• Invert the infusion bag gently to mix the solution after refrigeration.

Administration instructions

• Vyxeos liposomal must not be mixed or administered as an infusion with other medicinal products.
• Administer Vyxeos liposomal by continuous intravenous infusion over 90 minutes using an infusion pump through a central venous catheter or a peripheral central catheter. A filter with a pore diameter of 15 µm or greater may be used for the intravenous infusion of Vyxeos liposomal.
• Flush the line after administration with 9 mg/ml (0.9%) sodium chloride solution for injections.

Disposal

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