MYOCET LIPOSOMAL 50 MG POWDER, DISPERSION AND SOLVENT FOR CONCENTRATE FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

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

Liposomal doxorubicin hydrochloride

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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 and other information

1. What Myocet liposomal is and what it is used for
2. What you need to know before you are given Myocet liposomal
3. How Myocet liposomal is given
4. Possible side effects
5. Storage of Myocet liposomal

1. Contents of the pack and other information

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

Myocet liposomal contains a medicine called doxorubicin, which damages cancer cells. This type of medicine is known as chemotherapy. The medicine is 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 cyclophosphamide. Read the package leaflet that comes with the medicine carefully.

2. What you need to know before you are given Myocet liposomal

You must not be given Myocet liposomal

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

You must not be given Myocet liposomal if you are in this situation. If you are unsure, consult your doctor or nurse before you are given Myocet liposomal.

Warnings and precautions

Talk to your doctor or nurse before you start using Myocet liposomal.

Talk to your doctor or nurse before you start using your medicine 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 situations (or if you are unsure), talk to your doctor or nurse before you are given Myocet liposomal.

Tests

Your doctor will perform tests during treatment to check that the medicine is working properly. They will also check for side effects such as circulation or heart problems.

Radiotherapy

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

Other medicines and Myocet liposomal

Using Myocet liposomal with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription and herbal medicines, as Myocet liposomal may affect the way other medicines work. Other medicines may also affect the way Myocet liposomal works.

Tell your doctor or nurse especially if you are taking any of the following medicines:

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

If you are in any of these situations (or if you are unsure), talk to your doctor or nurse before you are given Myocet liposomal.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before using this medicine.

• Myocet liposomal must not be used during pregnancy unless clearly necessary.
• Women treated with Myocet liposomal must 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 should seek genetic counseling and advice on fertility preservation before treatment.

Driving and using machines

After receiving 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 comes in boxes containing 1 set or 2 sets of 3 vials (some pack sizes may not be marketed). Once the 3 vials are mixed, the medicine contains approximately 108 mg of sodium (main component of table/cooking salt). This is equivalent to 5.4% of the maximum recommended daily intake of sodium for an adult.

3. How Myocet liposomal is given

This medicine will be given to you by a doctor or nurse. It is given by drip (infusion) into a vein.

How much will you be given

Your doctor will decide 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 medicine per square meter of body surface area:

• given once every three weeks
• the medicine cyclophosphamide is given on the same day.

Your doctor may give you a lower dose if they think it is necessary.

The number of times you will be given the infusion will depend on:

• the state of your breast cancer
• your body's response to the medicine.

Normally, the treatment lasts for 3 to 6 months.

If Myocet liposomal comes into contact with the skin

Tell your doctor or nurse immediately if the medicine spills from the drip (infusion) onto the skin. This is because Myocet liposomal can damage your skin. The drip will be stopped immediately. Ice will be applied to the affected area for 30 minutes. Then, the drip will be restarted in another vein.

If you have any other questions about using 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. The following side effects may occur with this medicine.

Tell your doctor or nurse immediately if you notice any of the following side effects, as they may be signs of an allergic reaction and may require the infusion to be stopped:

• shortness of breath or tightness in the chest or throat
• headache or back pain
• fever or chills
• flushing or redness of the face
• feeling tired, dizzy or faint.

If you experience any of these side effects, tell your doctor or nurse immediately.

Other side effects

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

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

low levels of certain blood cells - your doctor will perform regular blood tests to check for this. The signs may include:

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

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

• muscle pain, back pain, headache
• difficulty breathing, chest pain
• feeling thirsty, pain or inflammation of the digestive tract
• shortness of breath, swelling of the ankles, muscle cramps that may be signs of heart failure, heart rhythm disorders or low potassium levels in the blood
• abnormal liver function tests
• difficulty sleeping
• nosebleeds, hot flushes
• constipation, weight loss
• redness of the skin and changes in the nails.

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

• coughing up blood
• feeling agitated, feeling sleepy
• low blood pressure, feeling unwell
• difficulty walking, speech problems
• stomach pain that may be a sign of stomach ulcer formation
• muscle weakness
• itching and dryness of the skin or inflammation around the hair follicles
• inflammation, redness and blistering of the skin around the injection site
• high 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 (urine), painful urination or blood in the urine.

Frequency not known: cannot be estimated from the 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 improve if the infusion is given more slowly over a longer period of time.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are 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 Myocet 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 label and carton.
• Store in a refrigerator (between 2°C and 8°C).
• From a microbiological point of view, the product should be used immediately. If not, the time and conditions of storage prior to use, once reconstituted and diluted, are the responsibility of the user and should not exceed 24 hours, at a temperature of 2°C - 8°C, unless they have been reconstituted and diluted under aseptic controlled and validated conditions.

• Do not use this medicine if you notice any change in the color of the product or any signs of precipitation or particles in suspension.
• 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

Composition of Myocet liposomal

• The active substance is liposomal doxorubicin. This corresponds to 50 mg of doxorubicin hydrochloride.
• The other ingredients are lactose (in the doxorubicin hydrochloride vial), phosphatidylcholine, cholesterol, citric acid, sodium hydroxide and water for injections (in the liposome vial), sodium carbonate and water for injections (in the buffer vial).

Appearance and packaging

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

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

Myocet liposomal comes in packs containing 1 set or 2 sets of the three components. Some pack sizes may not be marketed.

Marketing authorisation holder

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Manufacturer

GP-Pharm

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

08777 Sant Quintí de Mediona (Barcelona) Spain

Date of last revision of this leaflet: {MM/YYYY}

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

This information is intended only for healthcare professionals:

PREPARATION GUIDE

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

Liposomal doxorubicin hydrochloride

It is important to read all of this guide before preparing this medicine.

1.

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

1. RECOMMENDATIONS FOR SAFE HANDLING

The following procedures should be adopted for the safe handling and disposal of antitumor medicines, i.e.:

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

3.

Aseptic technique should be strictly followed during the handling of Myocet liposomal, as it does not contain preservatives.

3.1

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 adjust the thermostat to 75°C-76°C. Check that the thermometer inserted into the thermal block reads the same temperature.
• If a water bath is used, heat the water bath and let it equilibrate to 58°C (55°C-60°C). Check the temperature using a thermometer.

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

• Remove the box containing the constituents from the refrigerator.

Step 2. Reconstitution of doxorubicin HCl

• Withdraw 20 ml of sodium chloride injection solution (0.9%), (not included in the packaging) and inject it into each vial of doxorubicin HCl 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 thermal block.

• Heat the reconstituted doxorubicin HCl vial in the Techne DB-3 Dri Block heater, keeping the thermometer inserted into the thermal 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 doxorubicin HCl vial, keeping the thermometer temperature at 55°C-60°C for 10 minutes (do not exceed 15 minutes).
• While heating, proceed to step 4.

Step 4. Adjusting the pH of the liposomes

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

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

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

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

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

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

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

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 performed under 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 subcutaneously, intramuscularly, or by bolus injection.

1. DISPOSAL

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.