Mitomicin Accord

Package Leaflet: Information for the User

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

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.

• 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 and other information

• 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 stopping the growth and spread of cancer cells. The treatment of cancer with medicines is based on the fact that cancer cells grow and multiply more quickly than normal cells. This medicine is used to treat various types of cancer.

Indications for use

Mitomycin is used to treat cancer to relieve symptoms (palliative treatment).

Intravenous administration

Mitomycin is given by injection into a vein, as a single chemotherapy treatment or in combination with other chemotherapy treatments. Mitomycin has been shown to be effective in the treatment of various types of cancer, including:

• advanced stomach cancer that has spread to other parts of the body,
• advanced and/or spreading breast cancer,
• lung cancer (non-small cell lung cancer),
• advanced pancreatic cancer.

Intravesical administration

The medicine is given directly into the bladder to prevent the recurrence of superficial bladder cancer in patients who have undergone a procedure to remove tissue from the bladder through the urethra (transurethral resection).

2. Before you take Mitomycin Accord

When not to use Mitomycin Accord

• during breastfeeding;
• for intravenous administration - if you have a significantly reduced number of all types of blood cells (pancytopenia) or a low white blood cell count (leukopenia) or platelet count (thrombocytopenia), a tendency to bleed (bleeding disorder), or a severe infection.
• for intravesical administration - if you have a perforation of the bladder wall.

Warnings and precautions

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

This medicine will be given to you under the supervision of a healthcare professional with experience in the use of 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 being treated with other forms of therapy (in particular, other cancer medicines or radiotherapy) that may also have a harmful effect on the body, the risk of side effects of mitomycin may be increased.

There are reports from animal studies of a loss of efficacy of mitomycin when given with vitamin B6.

During treatment with mitomycin, you should not be vaccinated with live vaccines.

This also applies to medicines used recently.

Pregnancy, breastfeeding, and fertility

Mitomycin should not be used during pregnancy. If treatment with mitomycin is necessary during pregnancy, your doctor will need to weigh the benefits against the risks of harm to the unborn child.

Women of childbearing age should avoid becoming pregnant. During treatment with mitomycin and for 6 months after the end of treatment, both men and women must use contraceptive measures.

If you become pregnant during treatment, you must inform your doctor.

Before starting treatment with mitomycin, you must stop breastfeeding.

Driving and using machines

Even when used as directed, mitomycin may cause nausea and vomiting, which can affect your ability to drive or operate machinery.

3. How to take Mitomycin Accord

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

Mitomycin is intended for administration by injection or infusion into a vein or into the bladder after reconstitution.

Your doctor will determine the dose and dosing schedule that is right for you.

Before administering mitomycin by injection or infusion into a vein, it is recommended to perform tests to check the function of your lungs, kidneys, and liver to rule out any diseases that may worsen during treatment with mitomycin.

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

Overdose

If you accidentally receive a higher dose than prescribed, you may experience symptoms such as fever, nausea, vomiting, and blood disorders. Your doctor may then prescribe 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, which can cause 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 crackling sounds when breathing in (interstitial lung disease) and severe kidney problems (nephrotoxicity) may occur.

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

Very common(affects more than 1 in 10 people)

• Blood disorders: reduced production of blood cells in the bone marrow; low white blood cell count (leukopenia), which increases the risk of infection; low 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 crackling sounds when breathing in (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 of the hands and soles of the feet (palmar-plantar erythrodysesthesia)
• Kidney problems (kidney failure, nephrotoxicity, glomerulopathy, elevated creatinine levels in the blood) - kidney failure
• Cellulitis and tissue necrosis after accidental injection into the tissues surrounding the vein (extravasation)

Uncommon(affects less than 1 in 100 people)

• Mouth ulcers
• 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)
• Low 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 cancer medicines (anthracycline antibiotics)
• Increased blood pressure in the lungs, which can cause shortness of breath, dizziness, and fainting (pulmonary hypertension)
• Disease of the pulmonary veins causing blockage (pulmonary veno-occlusive disease)
• Liver failure
• Increased liver enzyme activity - transaminases
• Yellowing of the skin and whites of the eyes (jaundice)
• Blockage of small veins in the liver (hepatic veno-occlusive disease) leading to fluid retention, liver enlargement, and increased bilirubin levels in the blood

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, which can cause difficulty breathing, loss of consciousness)

Side effects after intravesical administration

Common(affects less than 1 in 10 people)

• Skin rash (exanthema, allergic rash, contact dermatitis)
• Numbness, swelling, pain, and redness of the skin on the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia)
• Urinary tract infection, which may be accompanied by blood in the urine
• Painful urination, frequent urination at night (urinary frequency, nocturia)
• Blood in the urine (hematuria)
• 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 bladder inflammation, where the bladder wall may become necrotic (allergic bladder inflammation, necrotizing cystitis)
• Narrowing of the urinary tract
• Reduced bladder capacity
• Scarring of the bladder wall (bladder 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.

5. How to store Mitomycin Accord

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

No special storage precautions are required.

The product should be used immediately after reconstitution.

Do not use this medicine after the expiry date which is stated on the label and 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 packed in glass vials with an orange 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 Warszawa

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 must be avoided. If mitomycin is accidentally injected outside the vein, it can cause extensive tissue necrosis. To avoid this, the following precautions should be taken:

• Injections should only be given into large veins in the upper limbs.
• Injections should not be given directly into a vein, but into an intravenous line through which fluids are being administered.
• Before removing the cannula after administration of the product into a central vein, 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 administration of 200 mg of vitamin B6 into the general circulation may be helpful in stimulating the regeneration of damaged tissues. The product should not come into contact with the skin and mucous membranes.

Dosage and administration

The recommended dose 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 the risk of 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 recurrence 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 administration by injection or infusion or into the bladder 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 sodium chloride 0.9% solution or 20% glucose solution in the following proportions:

Intravesical administration:

The contents of the vial should be reconstituted with sodium chloride 0.9% solution and phosphate buffer pH 7.4 or water for injection in the following proportions:

Pregnant women in the healthcare team should not prepare or administer this medicinal product. The product should not come into contact with the skin. If it does, the skin should be washed several times with 8.4% sodium bicarbonate solution and then with soap and water. The exposed skin should not be treated with cream or emollient, as this may increase the absorption of the product into the skin.

In the event of contact with the eyes, they should be rinsed several times with sodium chloride 0.9% 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 solution 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 combination with other injections.
• Other solutions for injection or infusion should be administered separately.
• Accidental extravasation of mitomycin should be avoided.