Leaflet: information for the user

Myocet liposomal 50 mg powder,dispersion and solvent for concentrate for dispersion for infusion.

Liposomal hydrochloride of doxorubicin

Read this leaflet carefully before starting to use this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet.See section4.

6. Contents of the pack and additional information

Myocet liposomal contains a medicine called “doxorubicina”, which damages cancer cells. This type of medicine is known as “chemotherapy”. The medicine is found inside very small fat droplets called “liposomes”.

Myocet liposomal is used in adult women for the first-line treatment of breast cancer that has spread (metastatic breast cancer). It is used in combination with another medicine called “ciclofosfamida”. Read carefully the leaflet that accompanies the medicine.

Do not administer Myocet liposomal

• if you are allergic to doxorubicin or any of the other components of this medication (listed in section6).

Do not administer Myocet liposomal if you are in this case. In case of doubt, consult your doctor or nurse before Myocet liposomal is administered to you.

Warnings and precautions

Consult your doctor or nurse before starting to use Myocet liposomal.

Consult your doctor or nurse before starting to use this medication if:

• you have a fever, a history of heart problems (such as a heart attack, heart failure, or have had high blood pressure for a long time).
• you have liver problems.

If you are in any of these cases (or are unsure), consult your doctor or nurse before Myocet liposomal is administered to you.

Tests

Your doctor will perform tests during treatment to check that the medication is working properly. They will also monitor adverse effects such as circulatory or cardiac problems.

Radiation therapy

If you have already received radiation therapy, you may react to Myocet liposomal. You may have painful, red, or dry skin. This can occur immediately or later, at some point during your treatment.

Other medications andMyocet liposomal

Use of Myocet liposomal with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription and herbal remedies, as Myocet liposomal may affect how other medications work. Other medications may also affect how Myocet liposomal works.

Inform your doctor or nurse especially if you are taking any of the following medications:

• phenobarbital or phenytoin – for epilepsy
• warfarin – to thin the blood
• streptozotocin – for pancreatic cancer
• ciclosporin – to modify the immune system.

If you are in any of these cases (or are unsure), consult with your doctor or nurse before Myocet liposomal is administered to you.

Pregnancy and breastfeeding

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

• Myocet liposomal should not be used during pregnancy unless clearly necessary.
• Women treated with Myocet liposomal should not breastfeed.
• Women who may become pregnant should use effective contraceptive methods during treatment with Myocet liposomal and for 6.5 months after treatment.
• Women who wish to have children after treatment completion are advised to seek genetic counseling and advice on fertility preservation before treatment.

Driving and operating machinery

After administration of Myocet liposomal, you may feel dizzy. If you feel dizzy or are unsure how you feel, do not drive or use tools or machinery.

Myocet liposomal contains sodium

Myocet liposomal is presented in boxes containing 1 set or 2 sets of 3 vials (some sizes of packaging may only be marketed). Once the 3 vials are mixed, the medication contains approximately 108 mg of sodium (main component of table salt/cooking salt). This is equivalent to 5.4% of the maximum daily sodium intake recommended for an adult.

This medication will be administered to you by a doctor or nurse. It is administered through a drip (infusion) in a vein.

How much will be administered

Your doctor will decide on the exact dose you need. This is based on your body surface area (measured in “square meters” or “m2”).

The recommended dose is 60 to 75 mg of medication per square meter of body surface area:

• It is administered once every three weeks
• Cyclophosphamide medication is administered on the same day.

Your doctor may administer a lower dose if necessary.

The number of times the infusion will be administered will depend on:

• The state of your breast cancer
• Your body's response to the medication.

The treatment duration is usually 3 to 6 months.

If Myocet liposomal comes into contact with the skin

Inform your doctor or nurse immediately if the medication leaks from the infusion into the skin. This is because Myocet liposomal can damage your skin. The infusion will be stopped immediately. Ice will be applied to the affected area for 30 minutes. The infusion will then be restarted in another vein.

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

Like all medicines, this medicinecan cause side effects, although not everyone will experience them. With this medicine, the following side effects may occur.

Inform your doctor or nurse immediately if you notice any of the following side effects, as they are signs of an allergic reaction and may require discontinuation of the infusion:

• shortness of breath or chest tightness or throat constriction
• headache or back pain
• fever or chills
• inflammation or flushing of the face
• feeling tired, dizzy, or lightheaded.

Inform your doctor or nurse immediately if you experience any of these side effects.

Other side effects

Very common(may affect more than 1 in 10 patients):

• hair loss
• fever, chills, pain
• loss of appetite, diarrhea, feeling of nausea (nausea or vomiting)

reduced levels of certain blood cells - your doctor will perform frequent blood tests to determine this and decide if any treatment is required. Signs may include:

• increased bruising
• mouth pain, ulcers in the throat or mouth
• decreased resistance to infection or fever
• feeling tired or dizzy, lack of energy.

Common(may affect up to 1 in 10 patients):

• muscle pain, back pain, headache
• difficulty breathing, chest pain
• feeling thirsty, pain or inflammation of the digestive tract
• shortness of breath, inflammation of the ankles, muscle cramps that may be signs of heart failure, arrhythmias or low potassium levels in the blood
• abnormal liver function test results
• difficulty falling asleep
• nasal bleeding, hot flashes
• constipation, weight loss
• skin rash and nail changes.

Uncommon(may affect up to 1 in 100 patients):

• coughing up blood
• feeling agitated, feeling sleepy
• low blood pressure, feeling unwell
• difficulty walking, speech problems
• abdominal pain that may be a sign of stomach ulcer formation
• muscle weakness
• itching and dryness of the skin or inflammation around hair follicles
• inflammation, redness, and blistering of the skin around the injection site
• elevated blood sugar levels (your doctor will detect this in a blood test)
• yellowing of the skin or eyes, which may be signs of a liver disorder known as jaundice
• changes in urination frequency, painful urination, or presence of blood in the urine.

Frequency not known: cannot be estimated from available data:

redness and pain in hands and feet.

Myocet liposomal may cause some side effects related to the infusion rate. These include flushing, fever, chills, headache, and back pain. These side effects may resolve if the infusion is administered more slowly over a longer period of time.

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this leaflet.You can also report them directly through thenational reporting system included in theAppendixV. 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 label and the box.
• Store in refrigerator (between2°Cand8°C).
• From a microbiological standpoint, the product must be used immediately. If not, the time and storage conditions prior to use, once reconstituted and diluted, are the responsibility of the userand should not exceed 24 hours, at a temperature of2°C–8°C, unless reconstituted and diluted in controlled and validated aseptic conditions.

• Do not use this medication if you observe any change in the product color, or any sign of precipitation or particles in suspension.
• Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Myocetliposomal

• The active principle is doxorubicin encapsulated in liposomes. This corresponds to 50 mg of doxorubicin hydrochloride.
• The other components are lactose, (in the vial of HCl of doxorubicin) phosphatidylcholine, cholesterol, citric acid, sodium hydroxide, and water for injectable preparations (in the vial of liposomes), sodium carbonate, and water for injectable preparations (in the vial of buffer).

Aspect of the product and content of the package

Myocet liposomal consists of a powder, dispersion, and solvent for concentrate for dispersion for infusion, and is presented in a system of three vials: HCl of doxorubicin, liposomes, and buffer.

Once the contents of the vials are mixed, the resulting liposomal dispersion is opaque, orange-red in color.

Myocet liposomal is presented in packages that contain 1 set or 2 sets of the three components. Some package sizes may only be marketed.

Holder of the marketing authorization

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Responsible for manufacturing

GP-Pharm

Industrial Polygon Els Vinyets - Els Fogars,
Sector 2, Carretera Comarcal C244, km 22

08777 Sant Quintí de Mediona (Barcelona)
Spain

Last review date of this leaflet: {MM/AAAA}

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

This information is intended solely for healthcare professionals:

PREPARATION GUIDE

Myocet liposomal 50 mg powder, dispersion, and solvent for concentrate for dispersion for infusion

Doxorubicin hydrochloride liposomal

It is essential to read the entire content of this guide before preparing this medicine.

1.Presentation

Myocet liposomal is presented in a system of three vials: (1) HCl of doxorubicin, (2) liposomes, and (3) buffer. In addition to these three components, sodium chloride 0.9% (w/v) solution for injection is needed for the reconstitution of HCl of doxorubicin. Myocet liposomal must be reconstituted before administration.

1. RECOMMENDATIONS FOR SAFE HANDLING

Normal procedures for the correct handling and disposal of antitumor medicines should be adopted, i.e.:

• The personnel should be trained to reconstitute the medicine.
• Pregnant women should not handle the medicine.
• The personnel handling the medicine during reconstitution should wear protective clothing, including masks, glasses, and gloves.
• All administration or cleaning products, including gloves, will be deposited in a high-risk waste disposal bag for incineration at high temperatures. Liquid waste can be disposed of by pouring large quantities of water.
• Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.

3.PREPARATION FOR INTRAVENOUS ADMINISTRATION

The preparation of Myocet liposomal must be carried out strictly following aseptic technique, as it does not contain preservatives.

3.1Preparation of Myocet liposomal

Step 1. Preparation

Two alternative heating methods can be used: a Techne DB-3 Dri Block heater or a water bath:

• Turn on the Techne DB-3 Dri Block heater and set the thermostat to 75°C-76°C. Check that the thermometer inserted in the block marks this temperature.
• If a water bath is used, heat the water bath and let it equilibrate at 58°C (55°C-60°C). Check the temperature with a thermometer.

(Note that although the temperature control setting of the water bath and the block heater is different, the temperature of the vial contents will be within the same range (55°C-60°C)).

• Remove the box with the constituents from the refrigerator.

Step 2. Reconstitution of HCl of doxorubicin

• Withdraw 20 ml of sodium chloride 0.9% (w/v) solution for injection (not included in the package) and inject it into each vial of HCl of doxorubicin to be prepared.

• Shake well in an inverted position to ensure that the doxorubicin is completely dissolved.

Step 3. Heating in the water bath or block heater

• Heat the vial of reconstituted HCl of doxorubicin in the Techne DB-3 Dri Block heater, maintaining the thermometer inserted in the block at a temperature of 75°C-76°C for 10 minutes (do not exceed 15 minutes).
• If a water bath is used, heat the vial of HCl of doxorubicin, maintaining the thermometer at a temperature of 55°C-60°C for 10 minutes (do not exceed 15 minutes).
• While heating, proceed with step 4.

Step 4. Adjusting the pH of the liposomes

• Withdraw 1.9 ml from the vial of liposomes. Inject it into the vial of buffer to adjust the pH of the liposomes. In case of overpressure, remove the excess air.
• Shake well.

Step 5. Adding the liposomes with adjusted pH to the doxorubicin

• Using a syringe, withdraw the entire contents of the liposomes with adjusted pH from the vial of buffer.
• Remove the vial of reconstituted and heated HCl of doxorubicin from the water bath or block heater. SHAKE VIGOROUSLY. Carefully insert a ventilation device with a hydrophobic filter. IMMEDIATELY (within 2 minutes) inject the liposomes with adjusted pH into the reconstituted and heated vial of HCl of doxorubicin. Remove the ventilation device.
• SHAKE VIGOROUSLY.
• WAIT FOR AT LEAST 10 MINUTES BEFORE USING, MAINTAINING THE MEDICINE AT ROOM TEMPERATURE.

The reconstituted Myocet liposomal preparation contains 50 mg of doxorubicin hydrochloride / 25 ml of liposomal dispersion (2 mg/ml).

After reconstitution, the final product should be diluted in sodium chloride 0.9% (w/v) solution for injection or in glucose 5% (w/v) solution for injection to a final volume of 40 ml to 120 ml per 50 mg of reconstituted Myocet liposomal, so that a final concentration of 0.4 mg/ml to 1.2 mg/ml of doxorubicin is obtained.

Once diluted, the liposomal dispersion for infusion containing doxorubicin encapsulated in liposomes should be a homogeneous, opaque, and orange-red dispersion. Before administration, all parenteral solutions should be visually inspected for the presence of particles or changes in color. Do not use the preparation if you observe the presence of foreign particles.

It has been demonstrated that, once reconstituted, Myocet liposomal has physical and chemical stability for up to 8 hours at room temperature or up to 5 days in the refrigerator (2°C-8°C).

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not exceed 24 hours at 2°C-8°C, unless the reconstitution and dilution have been carried out in validated and controlled aseptic conditions.

Myocet liposomal should be administered by intravenous infusion over a period of one hour.

Warning: Myocet liposomal should not be administered by subcutaneous or intramuscular injection or by bolus injection.

1. DISPOSAL

The disposal of unused medicine and all materials that have been in contact with it should be carried out in accordance with local regulations.