Mitomycin accord

Package leaflet: Information for the user

Mitomycin Accord, 40 mg, powder for solution for injection / infusion
Mitomycinum
Please read all of this leaflet carefully before 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.
• 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 leaflet

1. What Mitomycin Accord is and what it is used for
2. What you need to know before you use Mitomycin Accord
3. How to use 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 in the treatment of cancer, i.e. a medicine which prevents or significantly delays the division of cancer cells by affecting their metabolism in various ways. The action of anticancer medicines is based on one of the differences between cancer cells and normal cells, namely the increased rate of cell division due to the lack of growth limitations.

Indications for use
Mitomycin is used in the treatment of malignant tumours to relieve symptoms (so-called palliative treatment).

Intravenous administration
Mitomycin is administered intravenously, either as monotherapy (i.e. chemotherapy using a single active substance) or in combination with other anticancer agents (i.e. combination chemotherapy). Mitomycin has shown activity in the following malignant tumours:

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

2. Important information before using Mitomycin Accord

When not to use Mitomycin Accord

• if the patient is allergic to mitomycin or to any of the other ingredients of this medicine (listed in section 6);
• during breastfeeding; breastfeeding must not be continued during treatment with mitomycin;
• in case of intravenous administration – if the patient has significant reduction in the number of all types of blood cells [red blood cells, white blood cells, and platelets (pancytopenia)] or isolated reduction in the number of white blood cells (leukopenia) or platelets (thrombocytopenia), tendency to bleed (hemorrhagic diathesis), or acute infection.

Warnings and precautions

Before starting treatment with Mitomycin Accord, consult a doctor or pharmacist.

Special caution is required when using Mitomycin Accord:

• if the patient has respiratory failure, renal failure, or hepatic failure;
• if the patient's general condition is poor;
• if the patient is undergoing radiotherapy;
• if the patient is being treated with other cytostatic agents (i.e. substances that inhibit cell growth and division);
• if the patient has suppressed bone marrow function (a condition in which the bone marrow is unable to produce blood cells necessary for the body), as this may worsen (especially in elderly patients and with prolonged mitomycin treatment); worsening of infection due to bone marrow suppression may occur, which could result in death;
• if the female patient is of childbearing potential, as mitomycin may negatively affect future fertility;
• if the patient has a tendency to bleed or has an infectious disease;
• if the patient has been vaccinated with a live viral vaccine, which may increase the risk of infections.

Mitomycin is a substance that may cause significant heritable changes in genetic material and may potentially cause cancer in humans.

The medicine will be administered to the patient under the supervision of a qualified healthcare professional experienced in chemotherapy, in order to reduce the risk of possible adverse effects at the injection site.

Children and adolescents

Mitomycin is not recommended for use in children and adolescents.

Mitomycin Accord and other medicines

Inform your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines the patient plans to take.

If the patient is receiving other treatments simultaneously (particularly other anticancer drugs or radiotherapy), which may also have harmful effects on the body, the adverse effects of mitomycin may be intensified.

Concomitant use with vinca alkaloids or bleomycin (drugs belonging to the cytostatic group) may intensify harmful effects on the lungs.

Cases of increased risk of a specific type of kidney disease (hemolytic-uremic syndrome) have been reported in patients receiving intravenous mitomycin together with 5-fluorouracil or tamoxifen.

There are animal study reports indicating loss of mitomycin activity when administered together with vitamin B__.

During treatment with mitomycin, do not receive vaccines containing live microorganisms, as this may increase the risk of infection.

The harmful effect of adriamycin (doxorubicin, a drug belonging to the cytostatic group) on the heart may be intensified by mitomycin.

The above also applies to medicines recently used.

Pregnancy, breastfeeding, and effects on fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor before taking this medicine.

Pregnancy

Mitomycin may cause heritable damage to genetic material and adversely affect embryonic development. Pregnancy must be avoided during treatment with mitomycin. Mitomycin should not be used during pregnancy. If treatment with mitomycin is necessary during pregnancy, the doctor will assess its benefits against the risk of harmful effects on the child. If the patient becomes pregnant during treatment despite this, she must immediately inform her doctor.

Women of childbearing potential should use effective contraception during treatment with mitomycin and for at least six months after completion of treatment.

Breastfeeding

Mitomycin is likely to pass into human milk. The patient must discontinue breastfeeding before starting mitomycin treatment.

Fertility

Mitomycin may cause heritable damage to genetic material. Men undergoing treatment with mitomycin are advised not to plan conception during treatment and for at least 3 months after its completion. It is also recommended to seek advice regarding sperm preservation before starting treatment due to the possibility of irreversible infertility caused by mitomycin treatment.

Driving and operating machinery

Even when mitomycin is used according to instructions, it may cause nausea and vomiting, shortening reaction time to such an extent that the ability to drive vehicles and operate machinery may be impaired. This is particularly true when alcohol is consumed concurrently.

3. How to use Mitomycin Accord

Mitomycin Accord should only be administered by physicians experienced in this type of treatment.
Mitomycin Accord is intended for injection or infusion into a blood vessel (intravenous administration) after prior reconstitution.
The physician determines the dose and dosing schedule appropriate for the individual patient.
Before administering mitomycin by injection or intravenous infusion, it is recommended to perform lung, kidney, and liver function tests to rule out the presence of diseases that could worsen during treatment with mitomycin.
During administration of mitomycin, the needle must remain properly inserted into the vein at all times. If the needle becomes dislodged from the vein or loosens, or if the medicine leaks into the surrounding tissues (which may be accompanied by discomfort or pain), the physician or nurse must be informed immediately.
Use of a higher than recommended dose of Mitomycin Accord
If a patient accidentally receives a higher dose, symptoms such as fever, nausea, vomiting, and blood disorders may occur. In such cases, the physician may recommend symptomatic treatment for these adverse effects.
If you have any further questions regarding the use of this medicine, consult your physician.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Possible side effects after intravenous administration
Severe allergic reactions (symptoms may include fainting, skin rash or hives, itching, swelling of the lips, face and airways with associated breathing difficulties, loss of consciousness – very rare (may affect up to 1 in 10,000 people)).
Severe lung disease may develop, characterised by shortness of breath, dry cough and inspiratory crackles (interstitial lung disease), and severe kidney function disorders (nephrotoxicity, when little or no urine is produced). If a patient notices any of the above-mentioned reactions, they should immediately inform their doctor, as treatment with mitomycin will then need to be discontinued.

Very common (affects more than 1 in 10 people)

• Suppression of blood cell production in the bone marrow (bone marrow suppression)
• Low white blood cell count (leukopenia), increasing the risk of infections
• Low platelet count (thrombocytopenia) causing bruising and bleeding
• Nausea and vomiting

Common (affects up to 1 in 10 people)

• Lung disease characterised by shortness of breath, dry cough and inspiratory crackles (interstitial lung disease)
• Breathing difficulties (dyspnoea), cough, laboured breathing
• Skin rashes (exanthema)
• Allergic skin rash
• Skin rash caused by contact with mitomycin (contact dermatitis)
• Numbness, swelling and painful redness of the palms and soles (palmar-plantar erythrodysesthesia)
• Kidney function disorders (renal failure, nephrotoxicity, glomerulopathy, increased blood creatinine levels) – renal failure
• Inflammation of connective tissue and tissue necrosis following accidental injection into tissues surrounding the vein (extravasation)

Uncommon (affects up to 1 in 100 people)

• Mucositis
• Stomatitis
• Diarrhoea
• Hair loss
• Fever
• Loss of appetite (anorexia)

Rare (affects up to 1 in 1,000 people)

• Life-threatening infections
• Blood poisoning (septicaemia, i.e. sepsis)
• Low red blood cell count, sometimes accompanied by acute kidney failure (haemolytic anaemia)
• Bruising (purpura) and red or purple spots (petechiae) on the skin (thrombotic thrombocytopenic purpura)
• A type of haemolytic anaemia caused by damage to blood cells in small blood vessels [microangiopathic haemolytic anaemia (MAHA)]
• A specific type of kidney failure [haemolytic-uraemic syndrome (HUS)], characterised by breakdown of red blood cells at a rate exceeding their production by the bone marrow (haemolytic anaemia), acute kidney failure and low platelet count
• Heart failure following previous treatment with other anticancer medicines (anthracycline antibiotics)
• Increased blood pressure in the pulmonary arteries, which may cause shortness of breath, dizziness and fainting (pulmonary hypertension)
• Pulmonary venous disease causing blockage of the veins (pulmonary veno-occlusive disease)
• Liver failure
• Increased liver enzyme activity – aminotransferases
• 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 blood bilirubin levels
• Generalised skin rash

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

• Severe allergic reactions (symptoms may include: fainting, skin rash or hives, itching, swelling of the lips, face and airways causing breathing difficulties, loss of consciousness)

Frequency not known (frequency cannot be estimated from available data)

• Infections
• Decreased number of blood cells (anaemia)

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, patients should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 authorisation holder.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Mitomycin Accord

Keep this medicine out of the sight and reach of children.
There are no special requirements for storage of this medicine.
Do not use this medicine after the expiry date stated on the cardboard carton and vial label after EXP. The expiry date refers to the last day of the specified month.
This medicine should be used immediately after preparation.
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 other information

What Mitomycin Accord contains
The active substance is mitomycin.
The other component is: mannitol.

What Mitomycin Accord looks like and contents of the pack
Mitomycin Accord is a blue-violet tablet or powder, which must be dissolved before administration. It is supplied in amber glass vials with a bromobutyl rubber stopper and an aluminium blue cap.
Mitomycin Accord 40 mg is available in packs of 1 or 5 vials, contained in a cardboard box.
Not all pack sizes may be marketed.

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

Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Accord Healthcare S.A. single member
64th Km National Road Athens, Lamia,
Schimatari, 32009
Greece

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

Information intended exclusively for medical professionals:

General information
Accidental extravascular administration of mitomycin must be avoided. Extravasation of the medicinal product may result in extensive tissue necrosis at the site of contact with the drug.
To prevent tissue necrosis, the following recommendations should be observed:

• administer injections only into large veins of the upper limbs;
• do not inject directly into a vein, but rather into an intravenous line that is currently being used safely and correctly for infusion;
• after administration of the product into a central vein, flush the catheter for several minutes with an infusion solution before removing it, in order to eliminate any residual mitomycin.

In case of extravasation, immediate local application of dimethyl sulfoxide (DMSO 99%) is recommended, repeated every 4–8 hours, along with the use of dry, cold compresses. Plastic surgery consultation should be sought early (within 72 hours). Intravenous administration of 200 mg vitamin B may assist in promoting regeneration of damaged tissues. Contact of the medicinal product with skin and mucous membranes must be avoided.

Dosage and method of administration
The recommended dosage for intravenous administration is 10 to 20 mg/m² of body surface area (BSA) every 6 to 8 weeks, 8 to 12 mg/m² every 3 to 4 weeks, or 5 to 10 mg/m² every 1 to 6 weeks. Doses exceeding 20 mg/m² increase the risk of toxic effects without providing additional therapeutic benefit. The maximum cumulative dose of mitomycin is 60 mg/m² BSA.

Mitomycin Accord powder is intended for administration as injection or infusion after prior reconstitution.
The medicinal product Mitomycin Accord 40 mg, powder for solution for injection/infusion, must not be reconstituted with water.
The contents of the 40 mg vial cannot be reconstituted to a concentration of 1 mg/ml. To achieve such a concentration, a medicinal product of different strength should be used.

The prepared solution is blue-violet in colour, clear and free from visible solid particles.
Pregnant female healthcare personnel should not prepare or administer this medicinal product.
Contact of the medicinal product Mitomycin Accord with the skin must be avoided. If contact occurs,
the skin should be rinsed several times with 8.4% sodium bicarbonate solution, then washed with soap and water.
The exposed skin should not be treated with hand cream or emollients, as this may increase drug penetration into the epidermis.
In case of eye contact, rinse eyes repeatedly with 0.9% sodium chloride solution.
The exposed individual should then be monitored for several days to detect any possible corneal damage.
If necessary, appropriate treatment should be initiated.
After preparation, the solution should be used immediately.
The contents of the vial are intended for single use only. Any unused solution should be discarded.
All unused medicinal product residues or waste materials should be disposed of in accordance with local regulations.

Notes

• Mitomycin Accord medicinal product must not be used in mixed injections.
• Other injectable solutions or infusion solutions must be administered separately.
• Accidental extravasation of mitomycin should be avoided.