Package Leaflet: Information for the User

Mitomicin Accord 20 mgpowder for intravesical solution and for injectable solution

Read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only; do not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any of the side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before using Mitomicin Accord

3. How to use Mitomicin Accord

4. Possible side effects

5. Storage of Mitomicin Accord

6. Contents of the pack and additional information

Mitomicina is a medication for cancer treatment, meaning it prevents or significantly delays the division of active cells by influencing their metabolism in several ways. The therapeutic application of cancer treatment medications is based on the fact that cancer cells differ from normal body cells in their higher rate of cellular division due to a lack of control over their growth.

Therapeutic indications

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

Intravenous administration

When administered intravenously, it is used in monotherapy, that is, treatment with a single active principle; or in polychemo-therapy, that is, 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 removal of tissue through the urethra (transurethral resection).

No use Mitomicina Accord:

• If you are allergic to mitomycin or any of the other components of this medication (listed in section 6).
• During breastfeeding.
• With 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 (leucopenia) or platelets (thrombocytopenia), a tendency to bleed (diathesis hemorrhagica) or acute infections (disease caused by pathogens).
• With 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 overall 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 inflammation of the bladder (in case of intravesical administration).
• If you have been told that you have myelodepression (your bone marrow cannot generate the blood cells you need); it may worsen (especially in elderly patients and during long-term treatment with mitomycin); infections may worsen due to myelodepression and may lead to fatal conditions.
• If you are fertile, as mitomycin may affect your ability to have children in the future.
• If you have a tendency to bleed and if an infectious disease occurs.
• If you have been immunized with a vaccine made with live viruses, as this increases the risk of infection.

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

Children and adolescents

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

Use of Mitomicina Accord with other medications

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

With the additional use of other types of treatment (specifically other cancer medications and radiation therapy) that also have adverse effects on you, it is possible that the adverse effects of mitomycin will be reinforced.

There are reports of animal experiments indicating that the effect of mitomycin is lost if it is administered concurrently with vitamin B6.

You should not be vaccinated, especially with vaccines made with live microorganisms, during treatment with mitomycin.

Be aware that the above also applies to medications you have used recently.

Pregnancy, breastfeeding, and fertility

Mitomycin should not be used during pregnancy. If treatment with mitomycin is necessary during pregnancy, your doctor should evaluate the benefit against the risk of adverse 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 6 months after its interruption. If you become pregnant during this period, you should inform your doctor immediately.

You should stop breastfeeding before starting to take mitomycin.

Driving and operating machinery

Although used as recommended, this medication may cause nausea and vomiting, so reaction times and the ability to drive cars and operate machinery may be affected. These effects are especially notable in combination with alcohol.

This medication should only be administered by healthcare professionals with experience in this type of treatment. Mitomicina Accord is intended for use by injection or infusion into a blood vessel (intravenous use) or for introduction into the bladder (intravesical instillation) after dissolution.

Your doctor will prescribe an appropriate dose and dosing regimen 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 pulmonary, renal, and hepatic function to exclude the presence of diseases that could worsen during treatment with mitomicina.

The needle should be kept in the vein while mitomicina is being administered. If the needle comes out or loosens, or if the medicinal product reaches the adjacent tissue 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 immediately or the Toxicological Information Service, phone 915 620 420.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

Possible side effects after administration through a vein

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

It may cause severe lung disease that 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 mitomycin must be interrupted.

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

•Blood disorders: Inhibition of blood cell production in the bone marrow; reduction of white blood cell count (leucopenia) that increases the risk of infections; reduction of platelet count (thrombocytopenia) that causes bruises 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

•Hives and skin irritation

•Numbness, swelling, and painful redness of palms of hands and soles of feet (palmoplantar syndrome)

•Kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased creatinine levels in the blood), inability of the kidneys to function

•Cellulitis and tissue death (necrotic tissue) 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 mucous membrane of the mouth (stomatitis)

•Diarrhea

•Hair loss (alopecia)

•Fever

•Loss of appetite (anorexia)

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

•Potentially fatal infection

•Septicemia

•Reduction of red blood cell count, sometimes accompanied by acute renal dysfunction (hemolytic anemia, microangiopathic hemolytic anemia (AHMA syndrome), hemolytic-uremic syndrome (HUS))

• Cardiac dysfunction (heart failure) after previous treatment with other cancer medications (anthracyclines)

•Increased blood pressure in the pulmonary vasculature, leading to difficulty breathing, dizziness, and fainting (pulmonary hypertension)

•Pulmonary vein obstruction disease(pulmonary veno-occlusive disease [PVOD])

•Liver disease (hepatic dysfunction)

•Increased levels of liver enzymes (transaminases)

•Yellowing of the skin and the white part of the eyes (jaundice)

•Blockage of small liver veins (liver veno-occlusive disease [VOD]) that leads to fluid retention, liver enlargement, and increased bilirubin levels in the blood

•Generalized hives

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

•Severe allergic reaction (symptoms may include dizziness, hives or urticaria, 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)

•Hives (exanthema, allergic hives, contact dermatitis)

•Numbness, swelling, and painful redness of palms of hands and soles of feet (erythrodysthesia palmoplantar [EPP]/hand-foot syndrome)

•Inflammation of the bladder (cystitis), which may be accompanied by blood in the bladder or urine

•Unpleasant odor when urinating, frequent urination, sometimes at night (diuresis, polyuria, nocturia)

•Blood in the urine (hematuria)

•Irritation of the bladder wall

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

•Generalized hives

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)

•Ureteral obstruction

•Reduced bladder capacity

•Hardening of the bladder wall (calcification of the bladder wall, fibrosis of the bladder wall)

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano Websitewww.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

This medication does not require special storage conditions.

Use immediately after reconstitution.

Do not use this medication after the expiration date that appears on the label after “EXP”. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Mitomicin Accord

-The active principle is mitomycin

- The other component is mannitol

Each vial contains 20 mg of mitomycin

Aspect of the product and contents of the packaging

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

The 20 mg vials are presented in packs containing 1 or 5 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, 6th floor

08039 Barcelona

Spain

Responsible for manufacturing

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) with the following names:

Last review date of this leaflet: May 2023

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

General information

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

• Always administer the injection in large veins of the arms.
• Do not administer the injection directly into the vein, but through the route of a functioning and safe infusion device.
• Before removing the cannula after administration via a central venous catheter, rinse it for a few minutes using the infusion to remove any remaining mitomycin.

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

It should be avoided to come into contact with the skin and mucous membranes.

Dosage and administration

The recommended dose for intravenous administration is 10-20 mg/m2of body surface area every 6-8 weeks, 8-12 mg/m2of body surface area every 3-4 weeks or 5-10 mg/m2of body surface area every 1-6 weeks. A dose greater than 20 mg/m2will produce more toxic manifestations and will not provide any therapeutic benefit. The maximum accumulated dose of mitomycin is 60 mg/m2.

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

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

Intravenous route:

Mitomycin Accord 20 mg powder for injectable solutioncannot be reconstituted with water.

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

20 ml for 20 mg of mitomycin.

Intravesical route:

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

20 ml for 20 mg of mitomycin.

Healthcare professionals who are pregnant should not handle or administer the medication. Mitomicin 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 drug into the epidermal tissue.

In the event of contact with the eyes, they should be rinsed several times with saline solution. They should then be observed for several days to see if any damage to the cornea appears. If necessary, the appropriate treatment should be applied.

The reconstituted product should be used immediately.

Note:

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