MITOMICINA ACCORD 40 mg POWDER FOR INJECTABLE SOLUTION AND FOR PERFUSION

Introduction

Package Leaflet: Information for the User

Mitomicina Accord 40mg powder for solution for injection and infusion

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 experience any of the side effects, talk to your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Mitomicina Accord and what is it used for

Mitomicina is a medicine used to treat cancer, it prevents or significantly delays the division of active cells by affecting their metabolism in several ways. The therapeutic application of cancer treatments is based on the fact that cancer cells differ from normal body cells in their higher rate of cell division due to a lack of growth control.

Therapeutic indications

Mitomicina is used in the treatment of cancer to alleviate symptoms (palliative cancer treatment).

Intravenous administration

When administered intravenously, it is used in monotherapy, i.e., treatment with a single active principle; or in cytostatic polychemotherapy, i.e., treatment with several active principles. Mitomicina is effective in the case of the following tumors:

• advanced metastatic stomach cancer (gastric carcinoma)
• advanced and/or metastatic breast cancer (breast carcinoma)
• respiratory tract cancer (non-microcytic bronchial carcinoma)
• advanced pancreatic cancer (pancreatic carcinoma)

2. What you need to know before you use Mitomicina Accord

Do not use Mitomicina Accord:

• if you are allergic to mitomicina or any of the other components of this medicine (listed in section 6).
• during breastfeeding.
• in the case of systemic administration, if you have a significant reduction in the number of all types of blood cells (including both red and white blood cells and platelets [pancytopenia]), if you have a significant reduction in white blood cells (leukopenia) or platelets (thrombocytopenia), tendency to bleed (hemorrhagic diathesis) or acute infections (disease caused by pathogens).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Mitomicina Accord.

• if you have reduced lung, kidney, or liver function.
• if your general state of health is not good.
• if you are undergoing radiation treatment.
• if you are being treated with other cytostatics (substances that inhibit cell growth or division).
• if you have been told you have bone marrow depression (your bone marrow cannot generate the blood cells you need); it may worsen (especially in elderly patients and during long-term treatment with mitomicina); infection may worsen due to bone marrow depression and lead to life-threatening situations.
• if you are of childbearing age, as mitomicina may affect your ability to have children in the future.
• if you have a tendency to bleeding and if an infectious disease occurs.
• if you have been immunized with a vaccine made from live viruses, as this increases the risk of infection.

You will receive treatment under the supervision of a healthcare professional with experience in this specific branch of medicine to minimize unwanted side effects at the injection site.

Children and adolescents

The use of mitomicina is not recommended in children and adolescents.

Other medicines and Mitomicina Accord

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

As a result of the additional use of other types of treatment (specifically other cancer medicines and radiotherapy) that also have harmful effects on you, it is possible that the adverse effects of mitomicina may be reinforced.

There are reports of animal experiments that indicate that the effect of mitomicina is lost if it is administered together with vitamin B6.

You should not be vaccinated, especially with vaccines made from live microbes, during treatment with mitomicina.

Note that the above also applies to medicines you have used recently.

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 medicine.

Mitomicina should not be used during pregnancy. If treatment with mitomicina is necessary during pregnancy, your doctor must evaluate the benefit versus the risk of harmful effects on your child.

Women of childbearing age should avoid becoming pregnant. Both men and women should use contraceptive methods during treatment and at least until 6 months after its interruption. If you become pregnant during this period, you must inform your doctor immediately.

You must stop breastfeeding before starting to take mitomicina.

Driving and using machines

Although this medicine is used following the recommendations, it can cause nausea and vomiting, so reaction times and the ability to drive cars and use machines may be affected. These effects are especially noticeable in combination with alcohol.

3. How to use Mitomicina Accord

This medicine should only be administered by healthcare professionals with experience in this type of treatment. This medicine is intended for use in injection or infusion into a blood vessel (intravenous use) after dissolution.

Your doctor will prescribe a dose and a dosing regimen suitable for you.

Before receiving mitomicina as an injection or infusion into a vein, it is recommended to perform a blood test and a review of lung, kidney, and liver functions to rule out the presence of diseases that may worsen during treatment with mitomicina.

The needle should remain in the vein while mitomicina is being administered. If the needle comes out or becomes loose, or if the medicine reaches the tissue adjacent to the vein (you may feel discomfort or pain), inform your doctor or nurse immediately.

If you receive more Mitomicina Accord than you should

If you have accidentally received a higher dose, you may experience symptoms such as fever, nausea, vomiting, and blood disorders. Your doctor may prescribe palliative treatment for any symptoms that may appear.

Consult your doctor or pharmacist or the Toxicology Information Service, phone 915 620 420, immediately.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Possible side effects after administration into a vein

Severe allergic reaction (symptoms can include fainting, rash or hives, itching, swelling of the lips, face, and respiratory tract with difficulty breathing or, in very rare cases (may affect 1 in 10,000 people), loss of consciousness).

Severe lung disease may occur, which presents as difficulty breathing, dry cough, and crackling sounds when breathing (interstitial pneumonia), as well as severe kidney dysfunction (nephrotoxicity). If you detect any of the above reactions, inform your doctor immediately, as treatment with mitomicina should be discontinued.

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

• Blood disorders: Inhibition of blood cell production in the bone marrow; reduction in the number of white blood cells (leukopenia) that increases the risk of infections; reduction in the number of platelets (thrombocytopenia) that causes bruising and bleeding.
• Nausea and vomiting

Common (may affect up to 1 in 10 people)

• Lung disorders that present as difficulty breathing, dry cough, and inspiratory crackling sounds (interstitial pneumonia)
• Dyspnea, cough, difficulty breathing
• Rashes and skin irritation
• Numbness, swelling, and painful redness of the palms of the hands and soles of the feet (palmar-plantar syndrome)
• Kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased creatinine levels in the blood), inability of the kidneys to function
• Inflammation of connective tissue (cellulitis) and tissue death (necrosis) after accidental injection into adjacent tissue (extravasation)

Uncommon (may affect up to 1 in 100 people)

• Inflammation of a mucous membrane (mucositis)
• Inflammation of the mouth mucosa (stomatitis)
• Diarrhea
• Hair loss (alopecia)
• Fever
• Loss of appetite (anorexia)

Rare (may affect up to 1 in 1,000 people)

• Potentially life-threatening infection
• Blood poisoning (sepsis)
• Decrease in the number of red blood cells, sometimes accompanied by acute kidney dysfunction (hemolytic anemia, microangiopathic hemolytic anemia syndrome [MAHA], hemolytic uremic syndrome [HUS])
• Loss of heart function (heart failure) after previous treatment with other cancer medicines (anthracyclines)

• Increased blood pressure in the pulmonary vasculature, leading to difficulty breathing, dizziness, and fainting (pulmonary hypertension)
• Obstructive disease of the pulmonary veins (pulmonary veno-occlusive disease [PVOD])
• Liver disease (liver dysfunction)
• Increased liver enzyme levels (transaminases)
• Yellowing of the skin and the white part of the eyes (jaundice)
• Blockage of the small veins of the liver (hepatic veno-occlusive disease [VOD]) leading to fluid retention, liver enlargement, and increased bilirubin levels in the blood
• Widespread rash

Very rare (may affect up to 1 in 10,000 people)

• Severe allergic reaction (symptoms can be fainting, rash or hives, itching, swelling of the lips, face, and respiratory tract with difficulty breathing, loss of consciousness)

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Mitomicina Accord

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

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the label after “EXP”. The expiry date is the last day of the month shown.

Use immediately after reconstitution.

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 further information

Composition of Mitomicina Accord

• The active substance is mitomicina
• The other component is mannitol (E421)

Appearance of the product and pack contents

Mitomicina Accord is a blue-violet powder that is mixed before injection. It is packaged in amber glass vials with a bromobutyl rubber stopper and a blue aluminum seal.

The 40 mg vials are packaged in boxes containing 1 or 5 vials.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice,

Poland

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: March 2022

This information is intended only for healthcare professionals:

General information

It is essential that the injection is administered intravenously. Perivascular administration of the medicine will produce extensive necrosis in the affected area. To avoid the appearance of necrosis, the following recommendations must be followed:

• Always administer the injection into large veins of the arms.
• Do not administer the injection directly into the vein, but through the line of a functioning and secure infusion equipment.
• Before removing the cannula after administration through a central venous catheter, flush it for a few minutes using the infusion to eliminate any residual mitomicina.

If extravasation occurs, it is recommended to infiltrate the area immediately with a 8.4% sodium bicarbonate solution and administer a 4 mg injection of dexamethasone afterwards. A systemic injection of 200 mg of vitamin B6 may be useful to stimulate the growth of new tissues after damage to existing ones.

Contact with the skin and mucous membranes should be avoided.

Posology and method of administration

The recommended dose for intravenous administration is 10-20 mg/m2 of body surface area every 6-8 weeks, 8-12 mg/m2 of body surface area every 3-4 weeks, or 5-10 mg/m2 of body surface area every 1-6 weeks. A dose greater than 20 mg/m2 produces more toxic manifestations and does not provide any therapeutic benefit. The maximum cumulative dose of mitomicina is 60 mg/m2.

Mitomicina is intended for intravenous injection or infusion after dissolution.

Mitomicina Accord 40 mg powder for solution for injection and infusion cannot be reconstituted in water.

The contents of the 40 mg vial must be reconstituted with 80 ml of saline or 20% glucose solution.

The contents of the 40 mg vial cannot be reconstituted to a concentration of 1 mg/ml. If this concentration is needed, other medicines must be used.

The reconstituted solution is blue-violet in color and free of visible particles.

Pregnant healthcare professionals should not handle or administer the medicine. Mitomicina Accord should not come into contact with the skin. If it does, the skin should be washed several times with a 8.4% sodium bicarbonate solution and then with water and soap. Hand creams or emollients should not be used, as they may facilitate the penetration of the medicine into the epidermal tissue.

In case of contact with the eyes, they should be rinsed several times with saline solution. Then, they should be observed for several days in case of corneal damage. If necessary, appropriate treatment should be applied.

The reconstituted product must be used immediately.

The contents of the vial are for single use. The unused solution must be discarded.

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

Note:

• Mitomicina Accord should not be used in combination injections.
• Other injection or infusion solutions should be administered separately.

It is essential that the injection is administered intravenously.