MITOMYCIN MEDAC 2 mg POWDER FOR INTRAVESICAL SOLUTION AND FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

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

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

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

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

mitomicina

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

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the package leaflet

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

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

Mitomicina medac is a medicine for the treatment of cancer, i.e., a medicine that prevents or significantly delays the division of active cells by influencing their metabolism in various ways (cytostatic). The therapeutic use of cytostatics in cancer therapy is based on the fact that one way cancer cells differ from normal body cells is that the rate of cell division increases due to a lack of growth control.

Therapeutic indications

Mitomicina medac is used in cancer therapy for the relief of symptoms (palliative cancer treatment).

Intravenous application

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 case of the following tumors:

• advanced cancer of the intestines (colorectal carcinoma)
• advanced cancer of the stomach (gastric carcinoma)
• advanced and/or metastatic breast cancer (breast carcinoma)
• advanced cancer of the esophagus (esophageal carcinoma)
• advanced cancer of the cervix (cervical carcinoma)
• non-small cell lung cancer (bronchial carcinoma)
• advanced cancer of the pancreas (pancreatic carcinoma)
• advanced tumors of the head and neck

Intravesical application

This medicine is introduced into the urinary bladder (intravesical application) to prevent the recurrence of superficial bladder cancer after the cancerous tissue has been removed through the urethra (transurethral resection).

2. What you need to know before you start using Mitomicina medac

Mitomicina can only be administered if it is strictly indicated, with continuous monitoring of blood counts if administered intravenously, and by experienced doctors in this type of treatment.

Do not use Mitomicina medac

• if you are allergic to mitomicina or to any of the other components of this medicine (listed in section 6),
• during breastfeeding: you must not breastfeed during treatment with mitomicina,
• in the case of intravenous administration (injection or infusion into a blood vessel):
• if you have a significant reduction in the number of all types of blood cells (including red and white blood cells and platelets [pancytopenia]), or an isolated reduction of white blood cells (leukopenia) or platelets (thrombocytopenia),
• if you have a tendency to bleed (hemorrhagic diathesis),
• in acute infections (diseases caused by pathogens),

• in the case of intravesical administration (application in 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

Consult your doctor or pharmacist before you start using Mitomicina medac.

Special precautions are required when using Mitomicina medac:

• if your general state of health is poor,
• if you suffer from impaired lung, kidney, or liver function,
• if you are undergoing radiotherapy,
• if you are being treated with other cytostatics (substances that inhibit cell growth/division),
• if you have been informed that you have myelodepression (your bone marrow cannot produce the blood cells you need). This may worsen (especially in elderly people and during long-term treatment with mitomicina); infections may worsen due to a reduction in blood counts and may lead to potentially life-threatening situations,
• if you are of childbearing age, as mitomicina may affect your future ability to have children.

Mitomicina is a substance that can cause significant hereditary changes in genetic material and may potentially cause cancer in humans.

Intravesical administration

If you experience abdominal pain or pain in the pelvic region that occurs immediately, or weeks or months after the application of Mitomicina medac in the bladder, inform your doctor immediately. Your doctor may need to perform an abdominal ultrasound to clarify the cause of the pain.

Avoid contact with the skin and mucous membranes.

Please read the general hygiene instructions after an intravesical instillation in the bladder:

It is recommended to sit down to urinate to avoid spilling urine and to wash your hands and genital area after urinating. This is especially applicable during the first urination after the administration of mitomicina.

Children and adolescents

The use of this medicine is not recommended in children and adolescents.

Other medicines and Mitomicina medac

No interactions with other medicines have been described if mitomicina is administered in 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 take or use any other medicine.

If other forms of treatment are used at the same time (in particular, other anticancer medicines, radiation), which also have a harmful effect on the bone marrow, the harmful effect of Mitomicina medac on the bone marrow may be intensified.

The combination with vinca alkaloids or bleomycin (medicines that belong to the group of cytostatics) may intensify the harmful effect on the lungs.

There have been reports of an increased risk of a specific type of kidney disease (hemolytic uremic syndrome) in patients receiving concomitant administration of intravenous mitomicina and 5-fluorouracil or tamoxifen.

There are reports from animal experiments indicating that the effect of mitomicina is lost when administered together with vitamin B6.

You should not be vaccinated with live vaccines during treatment with mitomicina, as this may increase your risk of being infected by the live vaccine.

The harmful effect on the heart of adriamycin (doxorubicin, a medicine from the group of cytostatics) may be intensified by mitomicina.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Mitomicina may cause hereditary genetic damage and may negatively affect the development of the embryo. You must not become pregnant during treatment with mitomicina. If you become pregnant, genetic counseling should be provided.

You must not use mitomicina during pregnancy. Your doctor must evaluate the benefit versus the risk of harmful effects on the fetus if treatment with mitomicina is necessary during pregnancy.

Breastfeeding

Mitomicina 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 take contraceptive measures or practice sexual abstinence during chemotherapy and the 6 months following.

Mitomicina may cause hereditary genetic damage. Consequently, as a male patient treated with mitomicina, you are advised not to procreate during treatment and the 6 months following, and to seek advice on sperm preservation before starting treatment, due to the possibility of irreversible infertility caused by mitomicina therapy.

Driving and using machines

Even when used according to the instructions, this medicine may cause nausea and vomiting, and consequently reduce reaction times to such an extent that the ability to drive a vehicle or use machines is affected. This is especially applicable if you consume alcohol at the same time.

3. How to use Mitomicina medac

Mitomicina medac is administered only by trained healthcare personnel.

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

Your doctor will prescribe the dose and treatment regimen that is right for you.

Intravenous administration

Before you are administered Mitomicina medac as an injection or infusion, it is recommended that blood tests and a check of lung, kidney, and liver function be performed to exclude any disease that could worsen during treatment with mitomicina.

The needle must remain in the blood vessel while Mitomicina medac is being administered. If the needle comes out or becomes loose, or if the medicine leaks into the surrounding tissue (you may feel discomfort or pain), inform your doctor or nurse immediately.

Intravesical administration

Mitomicina medac is introduced into the bladder at low pressure using a catheter. You must empty your bladder before treatment. The medicine must remain in the bladder for 1-2 hours. To achieve this, you should not drink too much liquid before, during, or after treatment. While the solution remains in the bladder, you should have sufficient contact with the entire surface of the mucosa, so moving around is good for the treatment. After 2 hours, you must empty your bladder while sitting down to avoid spilling.

If you use more Mitomicina medac than you should

If you have accidentally been administered a higher dose, 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 on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Possible Adverse Effects After Injection or Infusioninto a Blood Vessel(Intravenous Administration)

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

A severe pulmonary disorder may occur, presenting as shortness of breath, dry cough, and crackling sounds when inhaling (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 aforementioned reactions, inform your doctor immediately, as treatment with mitomycin should be suspended.

Very Common: May Affect More Than 1 in 10 People

• inhibition of blood cell production in the bone marrow (myelosuppression)
• decrease in the number of white blood cells (leukopenia), which increases the risk of infections
• decrease in the number of platelets (thrombocytopenia), which causes bruising and bleeding
• nausea and vomiting

Common: May Affect Up to 1 in 10 People

• pulmonary disorder presenting as shortness of breath, dry cough, and crackling sounds when inhaling (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 (kidney dysfunction, nephrotoxicity, glomerulopathy, increased creatinine levels in the blood), where little or no urine is produced

In Case of Mitomycin Injection or Drip into the Surrounding Tissue (Extravasation)

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

Uncommon: May Affect Up to 1 in 100 People

• inflammation of the 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
• septicemia
• decrease in the number of red blood cells due to abnormal destruction of these cells (hemolytic anemia)
• bruises (purpura) and red and purple spots (petechiae) on the skin (thrombocytopenic purpura)

cardiac failure after previous treatment with anticancer drugs (anthracyclines)

• increase in blood pressure in the lungs, which can cause shortness of breath, dizziness, and fainting (pulmonary hypertension)
• disease involving obstruction of the pulmonary veins (pulmonary veno-occlusive disease, PVOD)
• liver disease (liver dysfunction)
• increase in liver enzyme levels (transaminases)
• yellowing of the skin and whites of the eyes (jaundice)
• disease involving obstruction of the liver veins (hepatic veno-occlusive disease, HVOD)
• generalized rash (generalized exanthema)
• a particular form of kidney failure (hemolytic-uremic syndrome, HUS) characterized by destruction of red blood cells that exceeds the production of the bone marrow (hemolytic anemia), acute kidney failure, and a 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, inflammation 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 count (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 bladder instillation), as treatment with mitomycin should be suspended:

• 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 presenting as shortness of breath, dry cough, and crackling sounds when inhaling (interstitial pneumonia)
• severe kidney dysfunction: a kidney disease in which little or no urine is produced

Common: May Affect Up to 1 in 10 People

• bladder inflammation (cystitis), which may be accompanied by blood in the bladder or urine
• painful urination (dysuria)
• frequent urination at night (nocturia)
• excessive frequent urination (pollakiuria)
• blood in the urine (hematuria)
• local irritation of 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

• generalized rash (generalized exanthema)

Very Rare: May Affect Up to 1 in 10,000 People

• bladder inflammation with damage to the bladder tissue (necrotizing cystitis)
• allergic bladder inflammation (eosinophilic cystitis)
• narrowing (stenosis) of the urinary tract
• reduction in bladder capacity
• calcium deposits in the bladder wall (bladder wall calcification)
• partial conversion of the bladder wall tissue to connective tissue (bladder wall fibrosis)
• decrease in the number of white blood cells (leukopenia), which increases the risk of infections
• decrease in the number of platelets (thrombocytopenia), which causes bruising and bleeding
• systemic allergic reactions
• pulmonary disorder presenting as shortness of breath, dry cough, and crackling sounds when inhaling (interstitial lung disease)
• increase in liver enzyme levels (transaminases)
• hair loss (alopecia)
• nausea and vomiting
• diarrhea
• kidney disease (kidney dysfunction) where little or no urine is produced
• fever

Frequency Not Known: Cannot Be Estimated from Available Data

If Mitomycin Accidentally Enters Other Regions Besides the Bladder:

• bladder injury
• abscess in the abdomen
• tissue death (necrosis) of the surrounding area
• bladder fistula

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Medicines Surveillance System for Human Use: https://www.notificaRAM.es. By reporting adverse effects, you can contribute to providing 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 expiration date stated on the label and carton after EXP/CAD. The expiration date is the last day of the month indicated.

After reconstitution, this medicine should 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 the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Mitomycin medac

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

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

Appearance of the Product and Package Contents

Mitomicina medac is a gray to gray-blue powder for solution for injection or intravesical solution in a vial with a rubber stopper and an aluminum seal.

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

Each package of Mitomicina medac contains 1, 5, or 10 vials.

Only certain package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006-0

Fax: +49 4103 8006-100

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Laboratorios Gebro Pharma, S.A.

Avenida Tibidabo n° 29

08022 Barcelona

Spain

Tel.: +34 93 205 86 86

This medicine is authorized in the Member States of the European Economic Area 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 Last Revision of This Leaflet: 07/2024.

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

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This information is intended only for healthcare professionals:

Dosage

Intravenous Administration

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

The recommended doses are 10 - 20 mg/m² of body surface area every 6 - 8 weeks, 8 - 12 mg/m² of body surface area every 3 - 4 weeks, or 5 - 10 mg/m² of body surface area every 3 - 6 weeks, depending on the therapeutic scheme used.

In combination therapy, the dose is considerably lower. Due to the risk of cumulative myelotoxicity, it is not possible to deviate from proven treatment protocols without a specific reason.

Intravesical Administration

There are various regimens for intravesical administration of mitomycin, which vary in the dose of mitomycin used, the frequency of instillation, and the duration of treatment.

Unless otherwise specified, the dose of mitomycin is 40 mg, instilled into the bladder once a week. Regimens with instillations every two weeks, every month, or every 3 months may also be used.

The specialist should decide on the optimal regimen, frequency, and duration of treatment for each individual patient.

It is recommended to use this medicine at its optimal pH (urinary pH > 6) and to maintain the concentration of mitomycin in the bladder by reducing fluid intake before, during, and after instillation. The bladder should be emptied before instillation. Mitomycin is introduced into the bladder through a catheter and at low pressure. The duration of individual instillation should be 1 - 2 hours. During this period, the solution should have sufficient contact with the entire mucosal surface of the bladder. Therefore, the patient should be mobilized as much as possible. After 2 hours, the patient should evacuate the instilled solution, preferably in a sitting position.

Reconstitution of the Solution for Injection or Infusion Ready for Use

Mitomicina 2mg

Dissolve the contents of a 2 mg vial of Mitomicina medac in 2 ml of water for injections, inverting the vial.

Mitomicina 10mg

Dissolve the contents of a 10 mg vial of Mitomicina medac in 10 ml of water for injections, inverting the vial.

Mitomicina 20mg

Dissolve the contents of a 20 mg vial of Mitomicina medac in 20 ml of water for injections, inverting the vial.

Mitomicina 40mg

Dissolve the contents of a 40 mg vial of Mitomicina medac in 40 ml of water for injections, inverting the vial.

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

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

It is essential to avoid extravasation in the case of intravenous administration.

Reconstitution of the Solution for Intravesical Use Ready for Use

Mitomicina 2mg

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

Mitomicina 10mg

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

Mitomicina 20mg

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

Mitomicina 40mg

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

Notes

After reconstitution, the medicine should be used immediately.

Only clear solutions should be used. The contents of the vials are intended for single use only. The unused solution should be discarded.