MITOMICINA ACCORD 2 mg POWDER FOR INTRAVESICAL SOLUTION AND FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Mitomicina Accord 2 mgpowder for intravesical solution and for injectable solutionEFG

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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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 other information

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

Mitomicina is a medicine for the treatment of cancer, i.e., it prevents or considerably delays the division of active cells by influencing their metabolism in several ways. The therapeutic application of cancer treatment medicines is based on the fact that cancer cells differ from the body's normal 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)

Intravesical administration

Administration in the bladder (intravesical application) for the prevention of recurrence in the case of superficial bladder cancer after tissue ablation through the urethra (transurethral resection).

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), bleeding tendency (hemorrhagic diathesis) or acute infections (disease caused by pathogens).
• in the case of intravesical administration (application in the bladder), if you have a perforation of the bladder wall.

Warnings and precautions

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

• if you have a decrease in 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 bladder inflammation (in the case of intravesical administration).
• if you have been told you have bone marrow depression (your bone marrow cannot produce 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 may lead to life-threatening conditions.
• 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 the treatment under the supervision of a healthcare professional with experience in this particular 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.

Use of Mitomicina Accord with other medicines

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

With 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 experiments in animals 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

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 according to the recommendations, it may cause nausea and vomiting, so reaction times and the ability to drive vehicles 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. Mitomicina Accord is intended for use in injection or infusion into a blood vessel (intravenous use) or for introduction into the bladder (intravesical instillation) after dissolution.

Your doctor will prescribe a dose and 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 function to exclude 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 medicinal product 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 administer palliative treatment for any symptoms that may appear.

Consult your doctor or pharmacist or the Toxicology Information Service, telephone 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 in 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, loss of consciousness (may affect 1 in 10,000 people).

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 crackling sounds when breathing (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), kidney failure
• Inflammation of the connective tissue (cellulitis) and tissue death (necrosis) after accidental injection into the tissue adjacent to the vein (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
• Septicemia
• Decrease in the number of red blood cells, sometimes accompanied by acute kidney failure (hemolytic anemia, microangiopathic hemolytic anemia (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 levels of liver enzymes (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)) that leads to fluid retention, liver enlargement, and increased bilirubin levels in the blood
• Generalized 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)

Possible side effects after instillation in the bladder

Common (may affect up to 1 in 10 people)

• Rashes (exanthema, allergic rash, contact dermatitis)
• Numbness, swelling, and painful redness of the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia (PPE)/hand-foot syndrome)
• Bladder inflammation (cystitis), which may be accompanied by blood in the bladder or urine
• Painful urination, excessive frequent urination sometimes at night (dysuria, pollakiuria, nocturia)
• Blood in the urine (hematuria)
• Local irritation of the bladder wall

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

• Generalized rash

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

• Severe bladder inflammation in which parts of the bladder may suffer tissue death (allergic cystitis, necrotizing cystitis)
• Stenosis of the urinary tract
• Reduced bladder capacity
• Hardening of the bladder wall (calcification of the bladder wall, fibrosis of the bladder wall)

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Surveillance System for Human Use 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.

Use immediately after reconstitution.

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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Contents and Additional Information

Composition of Mitomycin Accord

• The active ingredient is mitomycin
• The other component is mannitol

Each vial contains 2 mg of mitomycin

Appearance of the Product and Container Contents

Mitomicina Accord is a powder that is mixed before injection. It is packaged in glass vials with a rubber stopper and aluminum cap.

The 2 mg vials are presented in packs containing 1, 5 or 10 vials.

Only some pack sizes may be marketed

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Cemelog BRS Ltd,

H-2040 Budaors, Vasut u. 13,

Hungary

or

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice,

Poland

This medicinal product is authorized in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Date of last revision of this leaflet: May 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals:

General Information

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

• Always administer the injection in large veins of the arms.
• Do not administer the injection directly into the vein, but through the perfusion equipment that functions correctly and safely.
• Before removing the cannula after administration through a central venous catheter, flush it for a few minutes using the infusion to eliminate any residue of mitomycin.

If extravasation occurs, it is recommended to infiltrate the area immediately with a solution of sodium bicarbonate 8.4% and administer an injection of 4 mg 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 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 mitomycin is 60 mg/m2.

The recommended dose for intravesical administration is 20-40 mg of mitomycin instilled weekly into the bladder for a period of 8 to 12 weeks. In the prevention of recurrent superficial bladder tumors, the alternative recommended dose is 4-10 mg (0.06-0.15 mg/kg body weight) instilled into the bladder through a urethral catheter 1 to 3 times a week. The solution should be kept in the bladder for 1-2 hours.

Mitomicina is intended for injection or intravenous perfusion or intravesical instillation after dissolution.

Intravenous route:

Mitomicina Accord 2 mg powder for injectable solution cannot be reconstituted in water.

The contents of the vial must be reconstituted with a saline or glucose solution 20% in a proportion of:

2 ml for 2 mg of mitomycin.

Intravesical route:

The contents of the vial must be reconstituted with saline solution or phosphate buffer 7.4 or water for injectable preparations in a proportion of:

2 ml for 2 mg of mitomycin.

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

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

The reconstituted product should be used immediately.

Note:

• Mitomicina Accord should not be used in combined injections.
• Other injection or infusion solutions should be administered separately.
• It is essential that the injection is administered intravenously.