Mitomycin medac 40 mg powder for intravesical solution and for injection solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Mitomicina medac 2 mg powder for intravesical solution and for injectable solution EFG

Mitomicina medac 10 mg powder for intravesical solution and for injectable solution EFG

Mitomicina medac 20 mg powder for intravesical solution and for injectable solution EFG

Mitomicina medac 40 mg powder for intravesical solution and for injectable solution EFG

mitomycin

Read the entire 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 questions, ask your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Mitomicina medac is and what it is used for
2. What you need to know before using Mitomicina medac
3. How to use Mitomicina medac
4. Possible adverse effects
5. How to store Mitomicina medac
6. Contents of the pack and other information

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

Mitomicina medac is a cancer treatment medicine, i.e., a medicine that prevents or considerably delays the division of actively proliferating cells by affecting their metabolism in various ways (cytostatic agent). The therapeutic use of cytostatic agents in oncology is based on the fact that one way in which cancer cells differ from normal body cells is that the rate of cell division is increased due to uncontrolled growth.

Therapeutic indications

Mitomicina medac is used in oncology for palliative treatment (treatment aimed at relieving symptoms).

Intravenous administration

When administered as an injection or infusion into a vein (intravenous administration), this medicine is used alone or in combination with other cytostatic medicines. This medicine is effective in the following tumours:

• Advanced bowel cancer (colorectal carcinoma)
• Advanced stomach cancer (gastric carcinoma)
• Advanced and/or metastatic breast cancer (breast carcinoma)
• Advanced oesophageal cancer (oesophageal carcinoma)
• Advanced cervical cancer (cervical carcinoma)
• Non-small cell lung cancer (bronchial carcinoma)
• Advanced pancreatic cancer (pancreatic carcinoma)
• Advanced head and neck tumours

Intravesical administration

This medicine is instilled into the urinary bladder (intravesical administration) to prevent recurrence of superficial bladder cancer after the cancer-affected tissue has been removed via the urethra (transurethral resection).

2. What you need to know before using Mitomicina medac

Mitomycin must only be administered if strictly indicated, with continuous monitoring of blood counts when given intravenously, and by physicians experienced in this type of treatment.

Do not use Mitomicina medac

• if you are allergic to mitomycin or to any of the other ingredients of this medicine (listed in section 6),

• during breastfeeding: you must not breastfeed during treatment with mitomycin,

• in the case of intravenous administration (injection or infusion into a blood vessel):

• if you have a significant reduction in all types of blood cells (including red and white blood cells and platelets [pancytopenia]), or a reduction in white blood cells (leucopenia) or platelets (thrombocytopenia) alone,

• if you have a tendency to bleed (haemorrhagic diathesis),

• during acute infections (illness caused by pathogens),

• in the case of intravesical administration (application into the urinary bladder):

• if you have a perforation of the bladder wall,

• if you suffer from inflammation of the urinary bladder (cystitis).

Warnings and precautions

Talk to your doctor or pharmacist before using Mitomicina medac.

Special precautions are required when using Mitomicina medac:

• if your general health condition is poor,
• if you have impaired pulmonary, renal or hepatic function,
• if you are undergoing radiotherapy,
• if you are being treated with other cytostatic agents (substances that inhibit cell growth/division),
• if you have been informed that you have myelosuppression (your bone marrow cannot produce the blood cells you need). This may worsen (especially in elderly patients and during long-term treatment with mitomycin); infections may become more severe due to reduced blood counts and may lead to potentially life-threatening situations,
• if you are of reproductive age, since mitomycin may affect your future ability to have children.

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

Intravesical administration

If you experience abdominal pain or pelvic pain occurring immediately after, or weeks or months after instillation of Mitomicina medac into the bladder, inform your doctor immediately. Your doctor may need to perform an abdominal ultrasound to determine the cause of the pain.

Avoid contact with skin and mucous membranes.

Please read the general hygiene instructions after intravesical instillation into the bladder:

It is recommended to sit while urinating to avoid spillage, and to wash your hands and genital area after urination. This is particularly important for the first urination after administration of mitomycin.

Children and adolescents

Use of this medicine is not recommended in children and adolescents.

Other medicines and Mitomicina medac

No interactions with other medicines have been reported when mitomycin is administered into the bladder (intravesical administration).

Possible interaction during injection or infusion into a blood vessel (intravenous administration)

Tell your doctor or pharmacist if you are taking or using, have recently taken or used, or might need to take or use any other medicines.

If other forms of treatment (particularly other anticancer drugs or radiation) that also have harmful effects on the bone marrow are used simultaneously, the harmful effect of Mitomicina medac on the bone marrow may be intensified.

Combination with vinca alkaloids or bleomycin (medicines belonging to the group of cytostatics) may intensify the harmful effect on the lungs.

An increased risk of a specific type of kidney disease (haemolytic uraemic syndrome) has been reported in patients receiving concomitant intravenous mitomycin and 5-fluorouracil or tamoxifen.

Animal experiments have indicated that the effect of mitomycin may be lost when administered together with vitamin B6.

You should not be vaccinated with live vaccines during treatment with mitomycin, as this may increase your risk of infection from the live vaccine.

The cardiotoxic effect of adriamycin (doxorubicin, a medicine belonging to the cytostatic group) may be intensified by mitomycin.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Mitomycin may cause heritable genetic damage and may adversely affect embryonic development. You must not become pregnant during treatment with mitomycin. If you become pregnant, genetic counselling should be provided.

Mitomicina medac must not be used during pregnancy. Your doctor must evaluate the benefit versus the risk of harmful effects on the fetus if treatment with mitomycin is necessary during pregnancy.

Breastfeeding

Mitomycin is likely to pass into breast milk. Breastfeeding must be discontinued during treatment with Mitomicina medac.

Fertility / contraception in men and women

As a sexually mature patient, you should use contraceptive measures or practise sexual abstinence during chemotherapy and for 6 months thereafter.

Mitomycin may cause heritable genetic damage. Therefore, as a man treated with mitomycin, you are advised not to father a child during treatment and for 6 months thereafter, and to seek advice on sperm preservation before starting treatment due to the possibility of irreversible infertility caused by mitomycin therapy.

Driving and using machines

Even when used according to instructions, this medicine may cause nausea and vomiting, thereby reducing reaction times to such an extent that your ability to drive or operate machinery may be impaired. This is particularly applicable if you consume alcohol at the same time.

3. How to use Mitomycin medac

Mitomycin medac is administered only by trained healthcare personnel.

This medicine must be used as an injection or infusion into a blood vessel (intravenous route) or for instillation into the urinary bladder (intravesical instillation) after reconstitution.

Your doctor will prescribe the dose and treatment schedule appropriate for you.

Intravenous administration

Prior to receiving Mitomycin medac as an injection or infusion, blood tests and monitoring of pulmonary, renal, and hepatic function are recommended to exclude any underlying conditions that could worsen during treatment with mitomycin.

The needle must remain in the blood vessel during administration of Mitomycin medac. If the needle becomes dislodged or loosened, or if the medicine leaks into the surrounding tissue (you may feel discomfort or pain), inform your doctor or nurse immediately.

Intravesical administration

Mitomycin medac is introduced into the bladder under low pressure using a catheter. You should empty your bladder before treatment. The medicine should remain in the bladder for 1–2 hours. To achieve this, you should not drink excessive fluids before, during, or after treatment. While the solution remains in the bladder, it should have adequate contact with the entire mucosal surface; therefore, moving around is beneficial for the treatment. After 2 hours, you should empty your bladder while sitting down to avoid spillage.

If you use more Mitomycin medac than you should

If an overdose has been accidentally administered, you may experience symptoms such as fever, nausea, vomiting, and blood disorders. Your doctor may provide supportive treatment for any symptoms that may occur.

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

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

Possible adverse effects after injection or infusion into a blood vessel (intravenous administration)

A severe allergic reaction may occur (symptoms may include fainting, skin rash or hives, itching, swelling of the lips, face and airways with difficulty breathing, loss of consciousness) (may affect up to 1 in 10,000 people).

A severe lung disorder may occur, presenting as shortness of breath, dry cough and crackling sounds on inhalation (interstitial pneumonia), as well as severe kidney dysfunction (a kidney disorder in which little or no urine is produced).

If you notice any of the reactions listed above, inform your doctor immediately, as treatment with mitomycin must be discontinued.

Very common: may affect more than 1 in 10 people

• suppression of blood cell production in the bone marrow (myelosuppression)
• decrease in the number of white blood cells (leukopenia), increasing the risk of infections
• decrease in the number of platelets (thrombocytopenia), leading to bruising and bleeding
• nausea and vomiting

Common: may affect up to 1 in 10 people

• lung disorder presenting as shortness of breath, dry cough and crackling sounds on inhalation (interstitial pneumonia)
• difficulty breathing (dyspnea), cough, shortness of breath
• skin rash (exanthema)
• allergic skin rash
• skin rash due to contact with mitomycin (contact dermatitis)
• numbness, swelling and painful redness of palms and soles (palmar-plantar erythema)
• kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased blood creatinine levels), with little or no urine production

In case of injection or leakage of mitomycin into surrounding tissue (extravasation)

• inflammation of connective tissue (cellulitis)
• tissue death (tissue necrosis)

Uncommon: may affect up to 1 in 100 people

• inflammation of mucous membranes (mucositis)
• inflammation of the mucous membranes of the mouth (stomatitis)
• diarrhea
• hair loss (alopecia)
• fever
• loss of appetite

Rare: may affect up to 1 in 1,000 people

• potentially life-threatening infection
• sepsis
• decrease in red blood cells due to abnormal destruction of these cells (hemolytic anemia)
• bruising (purpura) and red or purple spots (petechiae) on the skin (thrombotic thrombocytopenic purpura)
• heart failure following prior treatment with anticancer medicines (anthracyclines)
• increased blood pressure in the lungs, for example causing shortness of breath, dizziness and fainting (pulmonary hypertension)
• a disease involving obstruction of the veins in the lungs (pulmonary veno-occlusive disease, PVOD)
• liver disease (hepatic dysfunction)
• increased levels of liver enzymes (transaminases)
• yellowing of the skin and whites of the eyes (jaundice)
• a disease involving obstruction of the liver veins (hepatic veno-occlusive disease, HVOD)
• rash all over the body (generalized exanthema)
• a specific type of kidney failure (hemolytic uremic syndrome, HUS), characterized by destruction of red blood cells exceeding the production capacity of the bone marrow (hemolytic anemia), acute kidney failure, and low platelet count
• a type of hemolytic anemia caused by factors in small blood vessels (microangiopathic hemolytic anemia, MAHA)

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

• severe allergic reaction (symptoms may include fainting, skin rash or hives, itching, swelling of the lips, face and airways with difficulty breathing, loss of consciousness)

Frequency not known: cannot be estimated from available data

• infections
• reduction in blood cell counts (anemia)

Possible adverse effects after instillation into the bladder (intravesical administration)

Inform your doctor immediately if you notice any of the following reactions (which have been observed very rarely after instillation into the bladder), as treatment with mitomycin must be discontinued:

• severe allergic reaction, with symptoms such as fainting, skin rash or hives, itching, swelling of the lips, face and airways with difficulty breathing, loss of consciousness
• severe lung disease manifesting as shortness of breath, dry cough and crackling sounds on inhalation (interstitial pneumonia)
• Severe renal dysfunction: kidney disease with little or no urine output

Common: may affect up to 1 in 10 people

• inflammation of the bladder (cystitis), which may be accompanied by blood in the bladder or urine
• pain when urinating (dysuria)
• frequent urination at night (nocturia)
• excessively frequent urination (polyuria)
• blood in the urine (hematuria)
• local irritation in the bladder wall
• local skin rash (local exanthema)
• allergic skin rash
• skin rash due to contact with mitomycin (contact dermatitis)
• numbness, swelling and painful redness of palms and soles (palmar-plantar erythema)

Rare: may affect up to 1 in 1,000 people

• rash all over the body (generalized exanthema)

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

• inflammation of the bladder with damage to bladder tissue (necrotizing cystitis)
• allergic (eosinophilic) inflammation of the bladder (cystitis)
• narrowing (stenosis) of the urinary tract
• reduced bladder capacity
• calcium deposits in the bladder wall (vesical wall calcification)
• partial conversion of bladder wall tissue into connective tissue (vesical wall fibrosis)
• decrease in the number of white blood cells (leukopenia), increasing the risk of infections
• decrease in the number of platelets (thrombocytopenia), leading to bruising and bleeding
• systemic allergic reactions
• lung disorder presenting as shortness of breath, dry cough and crackling sounds on inhalation (interstitial lung disease)
• increased levels of liver enzymes (elevated transaminases)
• hair loss (alopecia)
• nausea and vomiting
• diarrhea
• kidney disease (renal dysfunction) with little or no urine output
• fever

Frequency not known: cannot be estimated from available data

If mitomycin accidentally reaches areas other than the bladder:

• bladder injury
• pus-filled pocket in the abdomen (abscess)
• death of (adipose) tissue in the surrounding area (necrosis)
• vesical fistula

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Mitomycin medac

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

Store the vial in the outer packaging to protect it from light.

Do not use this medicine after the expiry date stated on the label and carton after EXP/CAD. The expiry date is the last day of the month indicated.

After reconstitution, this medicine must be used immediately.

Protect the reconstituted solution from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Mitomycin medac

• The active substance is mitomycin.
• The other component is urea.

Each vial contains 2 mg (10 mg, 20 mg, 40 mg) of mitomycin.

Appearance of the medicinal product and contents of the container

Mitomycin medac is a grey to bluish-grey powder for injectable solution or solution for intravesical use in a vial with a coated rubber stopper and an aluminium seal.

Each vial contains 2, 10, 20 or 40 mg of mitomycin.

Each pack of Mitomycin medac contains 1, 5 or 10 vials.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006-0

Fax: +49 4103 8006-100

Further information about this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Laboratorios Gebro Pharma, S.A.

Avenida Tibidabo n° 29

08022 Barcelona

Spain

Tel.: +34 93 205 86 86

This medicinal product is authorised in the European Economic Area member states under the following names:

Germany, Austria, Belgium, Denmark, Slovakia, Estonia, Finland, Iceland, Latvia, Lithuania, Norway, Poland, Czech Republic:

Mitomycin medac

Spain, Italy, Portugal:

Mitomicina medac

Slovenia:

Mitomicin medac

Date of the most recent revision of this leaflet: 07/2024.

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

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This information is intended for healthcare professionals only:

Dosage

Intravenous administration

In monotherapy cytostatic treatment, mitomycin is usually administered intravenously as a bolus.

Recommended doses are 10–20 mg/m² body surface area every 6–8 weeks, 8–12 mg/m² body surface area every 3–4 weeks, or 5–10 mg/m² body surface area every 3–6 weeks, depending on the therapeutic regimen used.

In combination therapy, the dose is considerably lower. Due to the risk of cumulative myelotoxicity, deviations from established treatment protocols are not permissible without specific justification.

Intravesical administration

Various intravesical mitomycin regimens exist, differing in the dose of mitomycin used, instillation frequency, and treatment duration.

Unless otherwise specified, the dose of mitomycin is 40 mg, instilled into the bladder once weekly. Regimens with instillations every two weeks, monthly, or every three months may also be used.

The specialist must determine the optimal regimen, frequency, and duration of treatment for each individual patient.

It is recommended to use this medicinal product at its optimal pH (urinary pH > 6) and to maintain mitomycin concentration in the bladder by reducing fluid intake before, during, and after instillation. The bladder should be emptied prior to instillation. Mitomycin is introduced into the bladder via a catheter under low pressure. The duration of each instillation should be 1–2 hours. During this time, the solution should have adequate contact with the entire mucosal surface of the bladder. Therefore, the patient should be mobilized as much as possible. After 2 hours, the instilled solution should be evacuated, preferably while sitting.

Reconstitution of ready-to-use injectable or infusion solution

Mitomycin 2 mg

Dissolve the contents of one 2 mg vial of Mitomycin medac in 2 ml of water for injections by inverting the vial.

Mitomycin 10 mg

Dissolve the contents of one 10 mg vial of Mitomycin medac in 10 ml of water for injections by inverting the vial.

Mitomycin 20 mg

Dissolve the contents of one 20 mg vial of Mitomycin medac in 20 ml of water for injections by inverting the vial.

Mitomycin 40 mg

Dissolve the contents of one 40 mg vial of Mitomycin medac in 40 ml of water for injections by inverting the vial.

If the powder does not dissolve immediately, allow it to stand at room temperature until completely dissolved. The vial contents should form a clear, bluish-violet solution within 2 minutes.

Mitomycin medac must not be used mixed with other injectable solutions. Other injectable or infusion solutions should be administered separately.

Extravasation must be avoided during intravenous administration.

Reconstitution of ready-to-use intravesical solution

Mitomycin 2 mg

Dissolve the contents of 10–20 vials of Mitomycin medac 2 mg (equivalent to 20–40 mg of mitomycin) in 20–40 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution. The vial contents should form a clear, bluish-violet solution within 2 minutes.

Mitomycin 10 mg

Dissolve the contents of 2–4 vials of Mitomycin medac 10 mg (equivalent to 20–40 mg of mitomycin) in 20–40 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution. The vial contents should form a clear, bluish-violet solution within 2 minutes.

Mitomycin 20 mg

Dissolve the contents of 1–2 vials of Mitomycin medac 20 mg (equivalent to 20–40 mg of mitomycin) in 20–40 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution. The vial contents should form a clear, bluish-violet solution within 2 minutes.

Mitomycin 40 mg

Dissolve the contents of one 40 mg vial of Mitomycin medac (equivalent to 40 mg of mitomycin) in 40 ml of sterile 9 mg/ml (0.9%) sodium chloride injection solution. The vial contents should form a clear, bluish-violet solution within 2 minutes.

Notes

After reconstitution, the medicinal product must be used immediately.

Only clear solutions should be used. The vial contents are intended for single use/administration only. Unused solution must be discarded.