Product Information for the User

MEPACT 4 mg powder for concentrate for solution for infusion.

mifamurtida

Read this entire product information carefully before starting to use the medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.

• If you have any questions, consult your doctor.

• If you experience any adverse effects, consult your doctor, even if they are not listed in this product information. See section 4.

1. What you need to know before starting to use MEPACT

1. How to use MEPACT

1. Possible adverse effects

1. Storage of MEPACT

1. Contents of the package and additional information

MEPACT contains the active ingredient mifamurtida, similar to a component of the cell wall of some bacteria. It stimulates the immune system to help your body destroy cancer cells.

MEPACT is used for the treatment of osteosarcoma (bone cancer) in children, adolescents, and young adults (between 2 and 30 years). It is used after undergoing surgery to remove the tumor and being treated with chemotherapy to destroy any remaining cancer cells and thus reduce the risk of cancer recurrence.

No use MEPACT:

• If you are allergic (hypersensitive) to mifamurtida or any of the other components of this medication (listed in section 6).

• If you are using medications that contain ciclosporinas or other calcineurin inhibitors or high doses of non-steroidal anti-inflammatory drugs (NSAIDs) (see "Use of other medications" below).

Warnings and precautions

Consult your doctor before starting to use MEPACT:

• If you have or have had heart or blood vessel problems, such as blood clots (thrombosis), bleeding (hemorrhages) or inflammation of the veins (vasculitis). During MEPACT treatment, you will be closely monitored. If your symptoms do not improve over time or worsen, you should contact your doctor, as it may be necessary to delay or discontinue MEPACT treatment.

• If you have a history of asthma or other respiratory disorders. Before using MEPACT, consult your doctor about whether you should continue using asthma medications while using MEPACT.

MEPACT.

• If you have a history of inflammatory or autoimmune disease or have been treated with corticosteroids or other medications that can affect your immune system.

• If you have any allergic reaction to medications including rash, shortness of breath, and high blood pressure. If your symptoms worsen, you should contact your doctor, as they may have been caused by MEPACT.

• If you have stomach problems, such as nausea, vomiting, and loss of appetite. If your problems worsen, you should contact your doctor, as they may have been caused by MEPACT when used with chemotherapy.

• If you develop chills or shivering, or feel hot. You should take your temperature as you may have a fever. The presence of fever with a low white blood cell count (neutropenia) may be a sign of severe infection.

Section 4 includes detailed information on warnings and precautions related to adverse effects that may occur while taking this medication.

Children

Do not administer this medication to children under 2 years of age because there is no information on its safety and efficacy in this age group.

Other medications and MEPACT

Inform your doctor if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription. It is very important to inform your doctor if you are using medications that contain any of the following substances:

• Ciclosporina, tacrolimus, used after a transplant to prevent rejection of transplanted organs, and other immunosuppressants used, for example, to treat psoriasis (a skin disease).

• Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or diclofenac, used for the treatment of headaches, fever, or pain. Do not use MEPACT if you are using NSAIDs in high doses.

• Corticosteroids, for the treatment of inflammation, allergies, or asthma. Regular use of corticosteroids should be avoided when using MEPACT, as it may affect how the medications work.

It is recommended to separate the administration times of MEPACT and doxorubicin or other medications if they are combined in the same chemotherapy regimen.

Pregnancy, breastfeeding, and fertility

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

MEPACT has not been tested in pregnant women. Therefore, MEPACT should not be used during pregnancy, or in women of childbearing age who do not use an effective contraceptive method. Use an effective contraceptive method if you receive treatment with MEPACT.

It is not known if MEPACT passes into breast milk. If you are breastfeeding your child, consult your doctor.

Driving and operating machinery

Some very common or common adverse effects of MEPACT treatment (such as dizziness, vertigo, fatigue, and blurred vision) may affect your ability to drive and operate machinery.

MEPACT contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per dose; it is essentially "sodium-free".

Dose and treatment duration

MEPACT will only be administered under the supervision of a specialist doctor. Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

The recommended dose of MEPACT is 2 mg/m2of body surface area. You will be administered it twice a week (with at least three days of difference) for the first 12 weeks, and then once a week for another 24 weeks.

The treatment program may be adjusted to fit your chemotherapy program. You do not need to interrupt the MEPACT program if your chemotherapy is delayed; you will have to complete 36 weeks (9 months) of MEPACT treatment without interruptions

How MEPACT is administered

The lyophilized powder must be reconstituted into a liquid suspension, filtered using the provided filter, and then diluted before use. MEPACT infusion is done directly into a vein (intravenously) for about 1 hour. This will be carried out by your doctor or a nurse, who will also monitor you during that time. You do not need to be hospitalized to receive MEPACT. It can also be administered to outpatients.

If you use more MEPACT than you should

You may experience more severe side effects, such as fever, chills, fatigue, nausea, vomiting, headache, high blood pressure, or low blood pressure. In case of overdose, contact your doctor or go to the nearest hospital.

If you interrupt treatment with MEPACT

You should not interrupt treatment with MEPACT before completing the treatment program without consulting your doctor first. If you have any other questions about using this product, ask your doctor.

Like all medicines, MEPACT can cause side effects, although not everyone will experience them.

Most patients experienced chills, fever, and fatigue, especially during the first administration of MEPACT. These effects are usually mild to moderate and transient and can be treated by your doctor; for example, with paracetamol for fever. When used with chemotherapy, MEPACT treatment often causes stomach problems, such as nausea, vomiting, and loss of appetite.

Consult your doctorimmediately:

• if the fever or chills persist for more than 8 hours after receiving the MEPACT dose, as it may indicate an infection, or
• if you experience a rash or present other respiratory problems (sibilancias) or

• if you experience any stomach problems.

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

• fever, chills/shivering, weakness, fatigue, or general discomfort

• nausea and/or vomiting, diarrhea, or constipation

• headache or dizziness

• rapid heart rate (tachycardia)

• high or low blood pressure

• loss of appetite

• sweating

• pain, which can be general pain, muscle pain, and/or joint pain, and back, chest, abdominal, arm, or leg pain
• cough, breathing difficulties, or shortness of breath

• low body temperature

• low red blood cell count

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

• blue discoloration of tissues, such as skin or gums, due to lack of oxygen

• appreciable increase in heart rate or force of heartbeats

• swelling in arms or legs, or in other areas

• chest discomfort

• stomach discomfort, loss of appetite, or weight loss

• redness, inflammation, infection, or other local reaction at the injection site or catheter insertion site.
• erythema or redness, skin inflammation, itching, dryness, pallor, or transient redness
• inflammation of the skin, tendons, muscles, or similar tissues that support the body structure
• inflammation of a vein

• upper abdominal or thoracic wall pain; distension or abdominal pain; indigestion or liver pain
• other types of pain, also in the neck, shoulder, groin, bones, or throat; postoperative pain

• muscle spasms or rigidity

• sensation of cold

• fatigue, dizziness, or somnolence

• burning, itching, or tingling sensation, reduced sensitivity to sensations, or sensation of sensitivity without stimuli
• involuntary muscle twitching

• dehydration

• low potassium levels in the blood

• inflammation of mucous membranes

• congestion or inflammation of the nose, throat, or sinuses

• upper respiratory tract infections (such as a cold) or urinary tract infections (such as a bladder infection)
• generalized infection

• Herpes simplex virus infection

• productive cough, wheezing, or difficulty breathing due to exertion or exacerbation

• runny nose or nasal bleeding

• fluid in the lung cavity

• blood in the urine, difficulty or pain urinating, or frequent urination

• difficulty sleeping, depression, anxiety, or confusion

• dizziness

• tinnitus

• blurred vision

• hair loss

• difficult menstruation, painful menstruation

• hearing loss

• low white blood cell count with or without fever, low platelet count

Unknown frequency(cannot be estimated from available data:

• excessive accumulation of fluid around the heart (pericardial effusion)

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in Appendix V.

By reporting side effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after “EXP”.

The expiration date is the last day of the month indicated.

Unopened vial:

Store in the refrigerator (between 2?°C and 8?°C). Do not freeze.

Store the vial in the outer packaging to protect it from light.

Reconstituted suspension:

Once reconstituted with a 9 mg/ml sodium chloride solution (0.9%), store at room temperature (approximately 20°C - 25°C) and use within a maximum of 6 hours. Do not use this medication if you observe visible signs of deterioration.

Medicines should not be disposed of through drains or in the trash. This will help protect the environment.

What MEPACT contains

• The active substance is mifamurtida. Each vial contains 4 mg of mifamurtida. After reconstitution, each ml contains 0.08 mg of mifamurtida.

• The other components are palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and

1,2-dioleoyl-sn-glycero-3-phosphate-L-serine sodium salt (OOPS). See section 2 “MEPACT contains sodium”.

Appearance of MEPACT and contents of the pack

MEPACT is a white to off-white powder or mass for concentrate for dispersion for infusion.

MEPACT is presented in a cardboard box containing:

• A 50 ml vial with a grey butyl rubber stopper, aluminium crimp and plastic flip-off.

• A sterile filter supplied in a blister.

Marketing authorisation holder:

Takeda France SAS

112 avenue Kléber

75116Paris

France

Responsible for manufacturing:

Takeda Austria GmbH

St. Peter-Straße 25

A-4020 Linz

Austria

Delpharm Novara S.r.l.

Via Crosa, 86

28065 Cerano (NO)

Italy

Date of the last revision of this leaflet:

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.

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The following information is directed exclusively to healthcare professionals:

Instructions for the preparation of MEPACT for intravenous infusion

Materials supplied in each pack -

• 1 vial of MEPACT (mifamurtida)

• 1 filter for MEPACT

Materials required but not supplied -

• Solution for injection of sodium chloride 9 mg/ml (0.9%), 100 ml bag

• 60 or 100 ml sterile syringe for single use with Luer lock

• 2 sterile injection needles of medium calibre (18)

It is recommended that the reconstitution of the liposomal suspension be carried out in a laminar flow cabinet using sterile gloves and aseptic techniques.

The lyophilised powder should be allowed to reach a temperature of approximately 20°C – 25°C before reconstitution, filtration using the provided filter and dilution. This takes about 30 minutes.

1. Remove the crimp from the vial and clean the stopper using an alcohol-soaked cotton swab.

1. Remove the filter from the blister, and remove the cap from the filter with needle.

Subsequently, insert the needle into the vial, piercing the stopper firmly until it is securely attached. At this point, the cap of the Luer lock of the filter should not be removed.

1. Remove the packaging from the 100 ml bag of solution for injection of sodium chloride 9 mg/ml (0.9%), the needle and syringe (not supplied in the pack).
2. Clean with an alcohol-soaked cotton swab the area of the bag of solution for injection of sodium chloride 9 mg/ml (0.9%) where the needle is to be inserted.
3. Using the needle and syringe, remove 50 ml of solution for injection of sodium chloride 9 mg/ml (0.9%) from the bag.
4. After removing the needle from the syringe, it should be attached to the filter by opening the cap of the Luer lock of the filter (figure 1).

7.Add the solution for injection of sodium chloride 9 mg/ml (0.9%) to the vial using a slow but firm pressure of the plunger of the syringe.Do not remove the filter or syringe from the vial.

1. Allow the vial to stand for 1 minute to ensure a deep hydration of the dry substance.
2. Subsequently, shake the vial vigorously for 1 minute while keeping the filter and syringe attached.This will form liposomes spontaneously (figure 2).

1. You can remove the required dose from the vial by inverting it and slowly withdrawing the plunger of the syringe (figure 3). After reconstitution, each ml of suspension contains 0.08 mg of mifamurtida. The volume of suspension to be removed according to the calculated dose is calculated as follows:

Volumen that must be removed = [12.5 x calculated dose (mg)] ml

For greater ease, the following table of concordance is provided:

1. Subsequently, remove the syringe from the filter and attach a new needle to the syringe containing the suspension. Clean the injection site of the bag with an alcohol-soaked cotton swab and inject the suspension from the syringe into the original bag containing the remaining 50 ml of solution for injection of sodium chloride 9 mg/ml (0.9%) (figure 4).

1. Mix the solution gently by rotating the bag several times.

1. Add the patient's identification, time and date to the label of the bag containing the reconstituted and diluted liposomal suspension.
2. Chemical and physical stability has been demonstrated for use within 6 hours at room temperature (approximately between 20°C – 25°C).
3. From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions for the conservation of the product once opened are the responsibility of the user and normally should not exceed 6 hours at room temperature.

No special requirements for its disposal.