Mepact

Package leaflet: Information for the user

MEPACT 4 mg powder for concentrate for dispersion for infusion

mifamurtide
Please 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 questions, ask your doctor.
• If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

What this leaflet contains:

1. What MEPACT is and what it is used for
2. What you need to know before you use MEPACT
3. How to use MEPACT
4. Possible side effects
5. How to store MEPACT
6. Contents of the pack and other information

1. What MEPACT is and what it is used for

MEPACT contains the active substance mifamurtide, which is similar to a component of the cell wall of certain bacteria. This substance stimulates the immune system to help the body destroy tumour cells.
MEPACT is used for the treatment of osteosarcoma (bone cancer) in children, adolescents, and young adults (aged 2 to 30 years). The medicine is used after surgical removal of a tumour and in combination with chemotherapy to kill any remaining cancer cells and reduce the risk of cancer recurrence.

2. What you need to know before using MEPACT

Do not use MEPACT

• if you are allergic to mifamurtide or to any of the other ingredients of this medicine (listed in section 6).
• if you are taking medicines containing cyclosporine or other calcineurin inhibitors or high-dose non-steroidal anti-inflammatory drugs (NSAIDs) (see section “Taking other medicines”).

Warnings and precautions
Talk to your doctor before using MEPACT:

• If you have had or currently have heart or blood vessel problems, such as blood clots (thrombosis), bleeding (haemorrhage), or inflammation of the veins (vasculitis). During treatment with MEPACT, you will be closely monitored by your doctor. If symptoms last longer or worsen, you must contact your doctor, as it may be necessary to delay or discontinue treatment with MEPACT.
• If you have a history of asthma or other respiratory disorders. Before using MEPACT, you should discuss with your doctor whether you may need to take asthma medication during treatment with MEPACT.
• If you have had inflammatory or autoimmune diseases or have been treated with corticosteroids or other medicines that may affect the immune system.
• If you have allergic reactions to any medicines, such as skin rash, shortness of breath, or high blood pressure. If symptoms worsen, you must contact your doctor, as these may have been caused by MEPACT.
• If you have stomach problems such as nausea, vomiting, or loss of appetite. If these problems increase, you must contact your doctor, as they may have been caused by MEPACT when used in combination with chemotherapy.
• If you experience chills, trembling, or feel cold. You should measure your temperature, as you may have a fever. Fever with low white blood cell count (neutropenia) may be a sign of a serious infection.

Detailed information on warnings and precautions regarding adverse effects that may
occur during treatment with the medicine is provided in section 4.
Children
It is recommended not to administer this medicine to children under 2 years of age,
as information on the safety and efficacy of this drug is not available for this age group.
Other medicines and MEPACT
Inform your doctor if you are taking, have recently taken, or might take any other
medicines, including those without a prescription. It is particularly important to inform your
doctor if you are taking medicines containing any of the following active substances:

• Cyclosporine, tacrolimus, used after transplantation to prevent rejection of transplanted organs, or other immunosuppressants used, for example, in the treatment of psoriasis (a skin disease).
• Non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, ibuprofen, or diclofenac, used to treat headache, fever, or pain. Do not use MEPACT if you are taking high-dose non-steroidal anti-inflammatory drugs (NSAIDs).
• Corticosteroids, used to treat inflammation, allergies, or asthma. Regular use of corticosteroids should be avoided when using MEPACT, as this may affect how the medicine works.

It is recommended to separate the administration times of MEPACT and doxorubicin or other
medicines if used within the same chemotherapy treatment regimen.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding,
consult your doctor before taking this medicine.
MEPACT has not been studied in pregnant women. Therefore, MEPACT must not be used
during pregnancy or in women of childbearing potential who are not using effective contraception.
You must use effective contraception if you are being treated with MEPACT.
It is not known whether MEPACT passes into human milk. If you are breastfeeding, you should discuss this with your doctor.
Driving and using machines
Some very common and common side effects of treatment with MEPACT (dizziness,
vertigo, fatigue, and blurred vision) may affect your ability to drive vehicles and
operate machinery.
MEPACT contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose unit, i.e., it is
essentially “sodium-free”.

3. How to use MEPACT

Dosage and duration of treatment
MEPACT will only be administered under the supervision of a specialist doctor.
Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor.
The recommended dose of MEPACT is 2 mg of mifamurtide per m² of body surface area. It will be administered twice weekly (with at least three days between doses) for the first 12 weeks, followed by once weekly for an additional 24 weeks.
The treatment schedule may be adjusted according to your chemotherapy regimen. There is no need to interrupt treatment with MEPACT if chemotherapy is delayed; you must complete 36 weeks (9 months) of MEPACT therapy without interruptions.

How MEPACT is administered
The lyophilized powder must be reconstituted into a liquid suspension, filtered using the filter provided, and further diluted before use. MEPACT is then administered by intravenous infusion over approximately 1 hour. This procedure will be performed by a doctor or nurse, who will monitor you throughout the infusion. Hospitalization is not required to receive MEPACT. It may also be administered to outpatients.

If you use more MEPACT than you should
You may experience more severe adverse effects, including fever, chills, fatigue, nausea, vomiting, headache, and elevated or lowered blood pressure. In case of overdose, contact your doctor or the nearest hospital immediately.

If you stop treatment with MEPACT
Do not stop treatment with MEPACT before completing the full course without first discussing it with your doctor. If you have any doubts about how to use this medicine, speak to your doctor.

4. Possible side effects

Like all medicines, MEPACT may cause side effects, although not everybody gets them.
Most patients experience chills, fever and fatigue, especially during the first administration of MEPACT. These effects are generally mild or moderate in severity, transient in nature, and can usually be managed by the physician, for example with paracetamol for fever.
When used in combination with chemotherapy, treatment with MEPACT may often cause stomach problems such as nausea, vomiting and loss of appetite.

Contact your doctor immediately:

• if you have fever or continuous chills lasting more than 8 hours after a dose of MEPACT, as this could be a sign of infection; or
• if you develop a rash or have difficulty breathing (wheezing); or
• if you experience stomach problems.

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

• fever, trembling, chills, weakness, fatigue or general malaise
• nausea and/or vomiting, diarrhoea or constipation
• headache or dizziness
• increased heart rate
• high or low blood pressure
• loss of appetite
• sweating
• general pain, including muscle and/or joint pain, and back, chest, abdominal, arm or leg pain
• cough, difficulty breathing or increased breathing rate
• low body temperature
• low red blood cell count

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

• bluish discoloration of tissues, e.g. skin or gums, caused by lack of oxygen
• noticeable increase in heartbeat frequency or strength
• swelling of arms or legs or other types of swelling
• chest discomfort
• stomach ache, reduced appetite or weight loss
• redness, swelling, infection or other local reaction at the injection site or catheter site
• rash or redness, skin inflammation, itching, dry skin, pale or temporary appearance
• redness
• inflammation of the skin, tendons, muscles or similar tissues supporting the body's structure
• inflammation of a vein
• upper abdominal or chest wall pain; abdominal swelling or pain; indigestion or liver pain
• other types of pain (neck, shoulders, groin, bones or sore throat); pain after surgery
• muscle spasms or stiffness
• feeling cold
• feeling tired, drowsy or sleepy
• burning sensation, tingling/numbness, reduced sensitivity or perception of sensations without stimulus
• involuntary tremor
• dehydration
• low potassium levels in the blood
• inflammation of mucous membranes
• nasal congestion or inflammation of the nose, throat or sinuses
• upper respiratory tract infections (e.g. cold) or urinary tract infections (e.g. bladder infection)
• generalized infection
• Herpes simplex virus infection
• productive cough, wheezing or exertional or worsened shortness of breath
• blood in sputum or nosebleeds
• fluid in the lung cavity
• blood in urine, difficulty or pain when urinating, or frequent urination
• difficulty sleeping, depression, anxiety or confusion
• dizziness
• ringing in the ears
• blurred vision
• hair loss
• menstrual problems, painful menstruation
• hearing loss
• low white blood cell count with or without fever, low platelet count

Not known (frequency cannot be estimated from the available data):

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor. You can also report side effects directly via the national reporting system listed in Annex V*. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MEPACT

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and outer packaging
of the vial after the words “EXP/SCAD”. The expiry date refers to the last day of that month.
Unopened vial
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the vial in the outer carton to protect the medicine from light.
Reconstituted suspension
After reconstitution in sodium chloride solution 9 mg/mL (0.9%), store the product at
room temperature (approximately 20 °C – 25 °C) and use within 6 hours.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater. This will help protect the environment.

6. Package contents and other information

What MEPACT contains

• The active substance is mifamurtide. Each vial contains 4 mg of mifamurtide. When reconstituted, each mL of suspension contains 0.08 mg of mifamurtide.
• The other components are 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine monosodium salt (OOPS). See section 2 “MEPACT contains sodium”.

Description of the appearance of MEPACT and contents of the pack
MEPACT is a homogeneous powder or compacted powder, white to off-white in colour, for concentrate for dispersion for infusion.
MEPACT is supplied in a carton containing:

• one 50 mL vial with grey butyl rubber stopper, aluminium seal and plastic flip-off cap;
• one sterile filter for MEPACT provided in a blister.

Marketing Authorisation Holder:
Esteve Pharmaceuticals S.A.
Passeig de la Zona Franca 109, Planta 4
08038 Barcelona
Spain

Manufacturer:
Kymos S.L.
Ronda de Can Fatjò 7b, Parc Tecnològic del Vallès
08290 Cerdanyola del Vallès
Spain

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Esteve Pharmaceuticals BV/SRL Esteve Pharmaceuticals S.A.
België /Belgique/Belgien Tel: +34 93 446 60 00
[email protected]

България Luxembourg/Luxemburg
Esteve Pharmaceuticals S.A. Esteve Pharmaceuticals BV/SRL
Tel: +34 93 446 60 00 België /Belgique/Belgien
[email protected]

Česká republika Magyarország
Akacia Group, s.r.o. Esteve Pharmaceuticals S.A.
Tel: +420 220 610 491 Tel: +34 93 446 60 00

Danmark Malta
Esteve Pharmaceuticals S.A. Esteve Pharmaceuticals S.A.
Tlf: +34 93 446 60 00 Tel: +34 93 446 60 00

Deutschland Nederland
Esteve Pharmaceuticals GmbH Esteve Pharmaceuticals S.A.
Deutschland Tel: +34 93 446 60 00
Tel.: +49 30 338427-100

Eesti Norge
Esteve Pharmaceuticals S.A. Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00 Tlf: +34 93 446 60 00

Ελλάδα Österreich
SPECIALTY THERAPEUTICS IKE Esteve Pharmaceuticals GmbH
Tel.: +30 2130233913 Deutschland
Tel.: +49 30 338427-100

España Polska
Esteve Pharmaceuticals S.A. IMED Poland Sp. z o.o.
Tel: +34 93 446 60 00 Tel: (+48) 22 663 43 10

France Portugal
Esteve Pharmaceuticals S.A.S Esteve Pharmaceuticals – Laboratório Farmacêutico Lda.
Tél: +33 1 42 31 07 10 Tel: +351 91 422 4766

Hrvatska România
Makpharm d.o.o. Esteve Pharmaceuticals S.A.
Tel: +385 1 4678 688 Tel: +34 93 446 60 00

Ireland Slovenija
Esteve Pharmaceuticals S.A. Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00 Tel: +34 93 446 60 00

Ísland Slovenská republika
Esteve Pharmaceuticals S.A. Medis Pharma Slovakia s.r.o.
Sími: +34 93 446 60 00 Tel: +421 2 32 39 3403

Italia Suomi/Finland
Esteve Pharmaceuticals SRL Esteve Pharmaceuticals S.A.
Tel: +39 345 9214959
Puh/Tel: +34 93 446 60 00

Κύπρος Sverige
SPECIALTY THERAPEUTICS IKE Esteve Pharmaceuticals S.A.
Tel.: +30 2130233913 Tel: +34 93 446 60 00

Latvija
Esteve Pharmaceuticals S.A.
Tel: +34 93 446 60 00

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Instructions for the preparation of MEPACT for intravenous infusion
Materials provided in each package

• 1 vial of MEPACT (mifamurtide)
• 1 filter for MEPACT

Materials required but not provided

• 100 mL bag of injectable sodium chloride solution 9 mg/mL (0.9%)
• 1 sterile disposable syringe of 60 or 100 mL with luer lock
• 2 sterile medium gauge (18) hypodermic needles

It is recommended to prepare the liposomal suspension in a laminar flow cabinet using sterile gloves and following aseptic techniques.
Allow the lyophilized powder to reach a temperature between approximately 20 °C and 25 °C before reconstitution, filtration using the provided filter, and dilution. This usually takes about 30 minutes.

1. Remove the vial cap and disinfect the stopper with an alcohol swab.
2. Remove the filter from its blister packaging and remove the cap from the filter’s needle. Then firmly insert the needle through the vial stopper until fully seated. Do not remove the luer connector cap of the filter yet.
3. Remove from its packaging the 100 mL bag of injectable sodium chloride solution 9 mg/mL (0.9%), the needle, and the syringe (not supplied in the package).
4. Disinfect with an alcohol swab the site on the sodium chloride 9 mg/mL (0.9%) solution bag where the needle will be inserted.
5. Using the needle and syringe, withdraw 50 mL of injectable sodium chloride solution 9 mg/mL (0.9%) from the bag.
6. After removing the needle from the syringe, connect the syringe to the filter by opening the luer connector cap of the filter (Figure 1).

Figure 1

7. Add the injectable sodium chloride solution 9 mg/mL (0.9%) to the vial by slowly and firmly depressing the plunger. Do not detach the filter and syringe from the vial.
8. Leave the vial undisturbed in an upright position for 1 minute to ensure proper hydration of the dried substance.
9. Then, vigorously shake the vial for 1 minute without detaching the filter and syringe. This process spontaneously forms the liposomes (Figure 2).

Figure 2

10. Withdraw the desired dose from the vial by inverting the vial and slowly pulling back the syringe plunger (Figure 3). Each mL of reconstituted suspension contains 0.08 mg of mifamurtide. The volume of suspension to withdraw for dosage amounts is calculated as follows:

Volume to withdraw = [12.5 × calculated dose (mg)] mL
For convenience, refer to the following equivalence table:

Figure 3

11. Then, detach 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 swab and inject the suspension from the syringe into the original bag containing the remaining 50 mL of sodium chloride 9 mg/mL (0.9%) injectable solution (Figure 4).

Figure 4

12. Gently rotate the bag to mix the solution.
13. Add the patient's identification details, date, and time on the label of the bag containing the reconstituted and diluted liposomal suspension.
14. Chemical and physical in-use stability has been demonstrated for 6 hours at room temperature (approximately 20 °C to 25 °C).
15. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 6 hours at room temperature.

No special instructions for disposal.