Mitomicin Accord

Package Leaflet: Information for the User

Mitomycin Accord, 10 mg, powder for solution for injection/infusion or for intravesical use

Urinary bladder

Mitomycin Accord, 20 mg, powder for solution for injection/infusion or for intravesical use

Mitomycin

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What Mitomycin Accord is and what it is used for
• 2. Before you take Mitomycin Accord
• 3. How to take Mitomycin Accord
• 4. Possible side effects
• 5. How to store Mitomycin Accord
• 6. Contents of the pack and other information

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

Mitomycin is a medicine used to treat cancer. It works by preventing the growth and division of cancer cells or by slowing their growth in various ways, affecting their metabolism. The action of anticancer medicines is based on the fact that one of the differences between cancer cells and normal cells is that cancer cells divide more quickly due to a lack of control over their division.

Indications for use

Mitomycin is used to treat malignant tumors to alleviate symptoms (palliative treatment).

Intravenous administration

Mitomycin is administered intravenously, either as single-agent chemotherapy (i.e., chemotherapy using one active substance) or as combination chemotherapy (i.e., chemotherapy using several active substances). Mitomycin has shown activity in the following malignant tumors:

• advanced metastatic gastric cancer,
• advanced and/or metastatic breast cancer,
• lung cancer (non-small cell lung cancer),
• advanced pancreatic cancer.

Intravesical administration

The medicine is administered into the bladder to prevent recurrences of superficial bladder cancer in patients after transurethral resection of the bladder (TUR).

2. Before you take Mitomycin Accord

When not to use Mitomycin Accord

• if you are allergic to mitomycin or any of the other ingredients of this medicine (listed in section 6);
• during breastfeeding;
• for intravenous administration - if you have significantly reduced blood cell counts (pancytopenia) or isolated reduced white blood cell count (leukopenia) or platelet count (thrombocytopenia), bleeding tendency (hemorrhagic diathesis), or acute infection.
• for intravesical administration - if you have a perforated bladder wall.

Warnings and precautions

Before starting treatment with Mitomycin Accord, tell your doctor or pharmacist if:

• you have respiratory, kidney, or liver failure,
• your general condition is poor,
• you are undergoing radiotherapy,
• you are being treated with other cytostatic agents (i.e., substances that inhibit cell growth and division),
• you have cystitis (in cases of intravesical administration),
• you have impaired bone marrow function (a condition in which the bone marrow is unable to produce the blood cells needed by the body), as this may worsen (especially in elderly patients and with prolonged mitomycin treatment); infection may also worsen due to impaired bone marrow function, which can be life-threatening.
• you are a woman of childbearing age, as mitomycin may negatively affect your ability to have children in the future.
• you have a tendency to bleed and have an infectious disease,
• you have been vaccinated with a live viral vaccine, which may increase the risk of infection.

The medicine will be administered to you under the supervision of a healthcare professional with experience in chemotherapy to minimize the risk of possible side effects at the injection site.

Children and adolescents

Mitomycin is not recommended for use in children and adolescents.

Mitomycin Accord and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.

If you are using other treatments (especially other anticancer medicines or radiotherapy) that can also harm your body, the risk of side effects from mitomycin may increase.

There are reports from animal studies on the loss of mitomycin activity when administered with vitamin B.

During mitomycin treatment, you should not receive live vaccines.

This also applies to medicines used recently.

Pregnancy, breastfeeding, and fertility

Mitomycin should not be used during pregnancy. If mitomycin treatment is necessary during pregnancy, your doctor will need to assess the benefits versus the risk of harmful effects on the fetus.

Women of childbearing age should avoid becoming pregnant. During mitomycin treatment and for six months after treatment ends, both men and women must use contraceptive measures. If a patient becomes pregnant during treatment, they must inform their doctor.

Before starting mitomycin, breastfeeding should be stopped.

Driving and using machines

Even when used as directed, mitomycin may cause nausea and vomiting, reducing reaction time to the point of impairing your ability to drive vehicles and operate machinery. This is especially true when combined with alcohol.

3. How to take Mitomycin Accord

Mitomycin should only be administered by doctors with experience in this type of treatment.

Mitomycin is intended for intravenous injection or infusion, or for intravesical use after reconstitution.

Your doctor will determine the dose and dosing schedule suitable for you.

Before administering mitomycin to you as an injection or infusion, lung, kidney, and liver function tests are recommended to rule out any conditions that may worsen with mitomycin treatment.

During mitomycin administration, the needle should remain in the vein at all times. If the needle is dislodged from the vein or becomes loose, or if the medicine leaks into the tissues around the vein (which may cause discomfort or pain), you should immediately inform your doctor or nurse.

Overdose

If you accidentally receive a higher dose, you may experience symptoms such as fever, nausea, vomiting, and blood disorders. Your doctor may then recommend symptomatic treatment for these side effects.

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

4. Possible side effects

Like all medicines, Mitomycin Accord can cause side effects, although not everybody gets them.

Side effects after intravenous administration

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

A severe lung disease characterized by shortness of breath, dry cough, and wheezing (interstitial lung disease) and severe kidney damage (nephrotoxicity) may occur.

If you notice any of the above reactions, you should immediately inform your doctor, as treatment with mitomycin may need to be discontinued.

Very common(affects more than 1 in 10 people)

• Blood disorders: bone marrow suppression; reduced white blood cell count (leukopenia), which increases the risk of infection; reduced platelet count (thrombocytopenia) causing bruising and bleeding
• Nausea, vomiting

Common(affects less than 1 in 10 people)

• Lung disease characterized by shortness of breath, dry cough, and wheezing (interstitial lung disease)
• Shortness of breath, cough, difficulty breathing
• Skin rash and skin irritation
• Numbness, swelling, and painful redness of the skin on the palms and soles (palmar-plantar erythrodysesthesia)
• Kidney damage (kidney failure, nephrotoxicity, glomerulopathy, elevated creatinine levels in the blood) - kidney failure
• Cellulitis and tissue necrosis after accidental extravasation

Uncommon(affects less than 1 in 100 people)

• Mucositis
• Oral mucositis
• Diarrhea
• Hair loss
• Fever
• Loss of appetite (anorexia)

Rare(affects less than 1 in 1,000 people)

• Life-threatening infections
• Blood poisoning (sepsis)
• Reduced red blood cell count, which may be accompanied by acute kidney failure (hemolytic anemia, microangiopathic hemolytic anemia, hemolytic-uremic syndrome)
• Heart failure after previous treatment with other anticancer medicines (anthracycline antibiotics)
• Increased blood pressure in the pulmonary vessels, which can cause shortness of breath, dizziness, and fainting (pulmonary hypertension)
• Pulmonary veno-occlusive disease
• Liver failure
• Increased liver enzyme activity - aminotransferases
• Jaundice (yellowing of the skin and eyes)
• Pulmonary veno-occlusive disease leading to fluid retention, liver enlargement, and increased bilirubin levels in the blood
• Generalized skin rash

Very rare(affects less than 1 in 10,000 people)

• Severe allergic reactions (symptoms may include fainting, skin rash or hives, itching, swelling of the lips, face, and respiratory tract with difficulty breathing, loss of consciousness)

Side effects after intravesical administration

Common(affects less than 1 in 10 people)

• Skin rash (exanthema, allergic skin rash, contact dermatitis)
• Numbness, swelling, pain, redness of the skin on the palms and soles (palmar-plantar erythrodysesthesia)
• Cystitis, which may be accompanied by blood in the urine
• Painful urination, frequent urination at night (urination problems, frequent urination, nocturia)
• Hematuria (blood in the urine)
• Local irritation of the bladder wall

Rare(affects less than 1 in 1,000 people)

• Generalized skin rash

Very rare(affects less than 1 in 10,000 people)

• Severe cystitis, where the bladder wall may become necrotic (allergic cystitis, necrotizing cystitis)
• Urethral stricture
• Reduced bladder capacity
• Bladder wall calcification or fibrosis

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mitomycin Accord

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

There are no special storage instructions.

The product should be used immediately after reconstitution.

Do not use this medicine after the expiry date which is stated on the label of the vial and the carton after EXP. The expiry date refers to the last day of that month.

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. Contents of the pack and other information

What Mitomycin Accord contains

The active substance is mitomycin.

The other ingredients are mannitol.

What Mitomycin Accord looks like and contents of the pack

Mitomycin Accord is a powder that must be reconstituted before use.

It is packaged in orange glass vials with a bromobutyl rubber stopper and an aluminum seal.

Mitomycin Accord 10 mg and 20 mg are available in packs of 1 or 5 vials, in a cardboard box.

Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o., ul. Taśmowa 7, 02-677 Warsaw, Tel: +48 22 577 28 00

Manufacturer

Accord Healthcare Limited, Sage House, 319 Pinner Road, North Harrow, HA1 4HF Middlesex, United Kingdom

Accord Healthcare Polska Sp. z o.o., ul. Lutomierska 50, 95-200 Pabianice

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

Date of last revision of the leaflet: May 2023

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Information intended for healthcare professionals only:

General information

Accidental extravasation of mitomycin should be avoided. If the product is extravasated, it can cause extensive tissue necrosis. To avoid necrosis, the following guidelines should be followed:

• Intravenous injections should only be performed into large veins in the upper limbs.
• Intravenous injections should not be administered directly into a vein but into an intravenous line through which fluids are being infused.
• Before removing the cannula after intravenous administration, it should be flushed with an infusion for a few minutes to remove any remaining mitomycin.

In the event of extravasation, the area of extravasation should be immediately injected with 8.4% sodium bicarbonate solution, followed by the injection of 4 mg of dexamethasone. The intravenous administration of 200 mg of vitamin B may be helpful in stimulating the regeneration of damaged tissues. The medicinal product should not come into contact with the skin and mucous membranes.

Dosage and administration

The recommended dosage for intravenous administration is 10-20 mg/m² body surface area every 6-8 weeks, 8-12 mg/m² every 3-4 weeks, or 5-10 mg/m² every 1-6 weeks. Doses greater than 20 mg/m² increase toxic effects without additional therapeutic benefits.

The maximum cumulative dose of mitomycin is 60 mg/m².

The recommended dose for intravesical administration is 20-40 mg of mitomycin once a week for 8 to 12 weeks. An alternative dosing schedule used to prevent recurrences of superficial bladder cancer is the administration of 4-10 mg (0.06-0.15 mg/kg body weight) of mitomycin via a catheter once or three times a week. The solution should remain in the bladder for 1-2 hours.

Mitomycin Accord powder is intended for intravenous injection or infusion, or for intravesical use after reconstitution.

Intravenous administration:

Mitomycin Accord 10/20 mg powder for solution for injection/infusion should not be reconstituted with water.

The contents of the vial should be reconstituted with saline solution or 20% glucose solution in the following proportions:

Intravesical administration:

The contents of the vial should be reconstituted with saline solution and phosphate buffer (pH 7.4) or water for injection in the following proportions:

Pregnant women in the medical staff should not prepare or administer this medicinal product. The medicinal product Mitomycin Accord should not come into contact with the skin. If contact occurs, the skin should be rinsed several times with 8.4% sodium bicarbonate solution and then washed with soap and water. The exposed skin should not be treated with hand cream or emollient, as this may increase the absorption of the medicinal product into the skin.

In case of eye contact, the eyes should be rinsed several times with saline solution. The person exposed should be observed for several days for possible corneal damage. If necessary, appropriate treatment should be initiated.

The reconstituted solution has a blue-violet color, is clear, and free of visible particles.

Any unused product or waste material should be disposed of in accordance with local requirements.

After dilution, the solution should be used immediately.

Notes:

• Mitomycin Accord should not be used in mixed injections.
• Other solutions for injection or infusion should be administered separately.
• Accidental extravasation of mitomycin should be avoided.