Package Leaflet: Information for the User

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

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

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

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

mitomicina

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

•Keep this leaflet, as you may need to read it again.

•If you have any questions, ask your doctor or pharmacist.

•If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section4.

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 side effects

5.Storage of Mitomicina medac

6. Contents of the pack and additional information

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

Therapeutic indications

Mitomicina medac is used in oncological therapy for symptom relief (palliative oncological treatment).

Intravenous application

When administered in the form of an injection or perfusion into a vein (intravenous administration), this medication is used alone or in combination with other cytostatic medications. This medication is effective in the case of the following tumors:

•Advanced colorectal cancer

•Advanced gastric cancer

•Advanced and/or metastatic breast cancer

•Advanced esophageal cancer

•Advanced cervical cancer

•Non-small cell lung cancer

•Advanced pancreatic cancer

•Advanced head and neck tumors

Intravesical application

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

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

Do not use Mitomicin Medac

•if you are allergic to mitomicin or any of the other components of this medication (listed in section6),

•during breastfeeding: do not breastfeed during mitomicin treatment,

•in the case of intravenous administration (injection or perfusion in 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 a isolated reduction of white blood cells (leucopenia) or platelets (thrombocytopenia),

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

•in acute infections (disease 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 have an inflammation of the urinary bladder (cystitis).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Mitomicin Medac.

Special precautions are required when using Mitomicin Medac:

•if your general state of health is poor,

•if you have a deterioration of lung, kidney, or liver function,

•if you are undergoing radiation therapy,

•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 can worsen (especially in older people and during long-term treatment with mitomicin); infections can worsen due to a reduction in blood counts and can lead to potentially fatal situations,

•if you are fertile, as mitomicin can affect your future ability to have children.

Mitomicin is a substance that can cause significant genetic changes in the genetic material, and can potentially cause cancer in humans.

Intravesical administration

If you experience abdominal pain or pelvic pain that appears immediately after, or weeks or months after the application of Mitomicin Medac in the urinary bladder, inform your doctor immediately. You may need your doctor 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 urinary bladder:

It is recommended to sit to urinate to avoid spilling urine and to wash your hands and genital area after urinating. This is particularly applicable in the first urination after mitomicin administration.

Children and adolescents

This medication is not recommended for use in children and adolescents.

Other medications and Mitomicin Medac

No interactions with other medications have been described if mitomicin is administered in the bladder (intravesical administration).

Possible interaction during injection or perfusion in a blood vessel (intravenous administration)

Inform your doctor or pharmacist if you are taking or using, have taken or used recently, or may need to take or use any other medication.

If other forms of treatment are used at the same time (particularly other anticancer medications, radiation) that also have a harmful effect on the bone marrow, it is possible that the harmful effect of Mitomicin Medac on the bone marrow will be intensified.

The combination with vinca alkaloids or bleomycin (medications that belong to the group of cytostatics) can 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 concurrent administration of intravenous mitomicin and 5‑fluorouracil or tamoxifen.

There are reports from animal experiments indicating that the effect of mitomicin is lost when administered with vitaminB6.

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

The harmful effect on the heart of adriamicin (doxorubicin, a medication in the group of cytostatics) can be intensified by mitomicin.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Mitomicin can cause genetic damage, and can negatively affect fetal development. You should not become pregnant during treatment with mitomicin. If you become pregnant, you should be provided with genetic counseling.

You should not use mitomicin during pregnancy. Your doctor should evaluate the benefit against the risk of harmful effects on the fetus, if necessary, the treatment with mitomicin during pregnancy.

Breastfeeding

Mitomicin is likely to pass into breast milk. You should interrupt breastfeeding during treatment with Mitomicin Medac.

Fertility / contraception in men and women

As a sexually mature patient, you should take contraceptive measures or practice abstinence during chemotherapy and for 6 months afterwards.

Mitomicin can cause genetic damage. Consequently, as a man treated with mitomicin, you are advised not to father children during treatment and for 6 months afterwards, and to seek advice on sperm conservation before starting treatment, due to the possibility of irreversible infertility caused by mitomicin therapy.

Driving and operating machines

Even when used as directed, this medication can cause nausea and vomiting, and therefore reduce reaction times to such an extent that the ability to drive a vehicle or operate machines is impaired. This is particularly applicable if you consume alcohol at the same time.

Mitomicin medac is administered only by trained healthcare personnel.

This medication must be used for 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 appropriate dose and treatment regimen for you.

Intravenous administration

Before Mitomicin medac is administered as an injection or infusion, it is recommended to perform blood tests and a check of pulmonary, renal, and hepatic function to exclude any underlying disease that could worsen during mitomicin treatment.

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

Intravesical administration

Mitomicin medac is introduced into the bladder at low pressure through a catheter. You must empty your bladder before treatment. The medication must remain in the bladder for 1-2 hours. To achieve this, do not drink too much liquid before, during, or after treatment. While the solution remains in the bladder, you must have sufficient contact with the entire surface of the mucosa, so moving around is beneficial for treatment. After 2 hours, you must empty your bladder while sitting to prevent spillage.

If you use more Mitomicin medac than you should

If you have accidentally received 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 other questions about the use of this medication, ask your doctor or pharmacist.

Like all medications, this medication may cause side effects, although not everyone will experience them.

Possible side effects after intravenous or intravenous administration in a blood vessel

A severe allergic reaction may occur (symptoms may include fainting, skin rash or urticaria, 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 lung disorder that presents as shortness of breath, dry cough, and crackling sounds when inhaling (interstitial pneumonia) and also severe kidney dysfunction (a kidney disorder in which little or no urine is produced).

If you notice any of the previously mentioned 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)

• Decreased white blood cell count (leucopenia), increasing the risk of infections

• Decreased platelet count (thrombocytopenia), causing bruises and bleeding

• Nausea and vomiting

Common: may affect up to 1 in 10 people

• Lung disorder that presents 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 (erythema palmo-plantar)

• Severe kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased creatinine levels in the blood), where little or no urine is produced

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

• Inflammation of connective tissue (cellulitis)

• Tissue death (necrosis)

Rare: may affect up to 1 in 100 people

• Inflammation of mucous membranes (mucositis)

• Inflammation of mucous membranes in the mouth (stomatitis)

• Diarrhea

• Hair loss (alopecia)

• Fever

• Loss of appetite

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

• Potentially fatal infection

• Septicemia

• Decreased red blood cell count due to abnormal destruction of these cells (hemolytic anemia)

• Purpura and petechiae (small red or purple spots) on the skin (purpura thrombocytopenic thrombocytopenia)

• Heart failure after previous treatment with anticancer medications (anthracyclines)

• Elevated blood pressure in the lungs, for example, causing shortness of breath, dizziness, and fainting (pulmonary hypertension)

• Disease involving obstruction of the pulmonary veins (pulmonary veno-occlusive disease, PVOD)

• Liver disease (hepatic dysfunction)

• Elevated liver enzyme levels (transaminases)

• Yellowing of the skin and white of the eyes (jaundice)

• Disease involving obstruction of the hepatic veins (hepatic veno-occlusive disease, HVOD)

• Generalized skin rash (exanthema generalizado)

• A particular form of kidney failure (uremic hemolytic syndrome, UHS) characterized bydestruction of red blood cells exceeding those produced by 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 urticaria, itching, inflammation of the lips, face, and airways with difficulty breathing, loss of consciousness)

Frequency unknown: cannot be estimated from available data

• Infections

• Reduced blood cell count (anemia)

Possible side effects after instillation in the bladder(intravesical administration)

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

• Severe allergic reaction, with symptoms such as fainting, skin rash or urticaria, itching, swelling of the lips, face, and airways with difficulty breathing, loss of consciousness

• Severe lung disorder that presents as shortness of breath, dry cough, and crackling sounds when inhaling (interstitial pneumonia)

• Severe kidney dysfunction: kidney disease in which little or no urine is produced

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

• Painful urination (dysuria)

• Frequent urination at night (nocturia)

• Excessively frequent urination (pollakiuria)

• Blood in the urine (hematuria)

• Local irritation in the bladder wall

• Local skin rash (exanthema local)

• Allergic skin rash

• Skin rash due to contact with mitomycin (contact dermatitis)

• Numbness, swelling, and painful redness of palms and soles (erythema palmo-plantar)

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

• Generalized skin rash (exanthema generalizado)

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

• Inflammation of the bladder with damage to the bladder tissue (necrotizing cystitis)

• Allergic inflammation of the bladder (eosinophilic cystitis)

• Narrowing (stenosis) of the urinary tract

• Reduced bladder capacity

• Calcification of the bladder wall (vesical calcification)

• Partial conversion of bladder wall tissue to connective tissue (vesical fibrosis)

• Decreased white blood cell count (leucopenia), increasing the risk of infections

• Decreased platelet count (thrombocytopenia), causing bruises and bleeding

• Systemic allergic reactions

• Lung disorder that presents as shortness of breath, dry cough, and crackling sounds when inhaling (interstitial lung disease)

• Elevated liver enzyme levels (increased transaminases)

• Hair loss (alopecia)

• Nausea and vomiting

• Diarrhea

• Kidney disease (renal dysfunction) where little or no urine is produced

• Fever

Frequency unknown: cannot be estimated from available data

If mitomycin accidentally reaches other areas besides the bladder:

• Bladder damage

• Abscess in the abdomen

• Death of surrounding fatty tissue (necrosis)

• Vesical fistula

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly throughthe Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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

Do not use this medication after the expiration date that appears on the label and on the box after EXP/CAD. The expiration date is the last day of the month indicated.

After reconstitution, this medication must be used immediately.

Protect the reconstituted solution from light.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Mitomicin Medac

•The active ingredient is mitomycin.

•The other component is urea.

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

Appearance of the product and contents of the packaging

Mitomicin Medac is a grey to blue-grey powder for injectable solution or intravesical solution in a vial with a rubber stopper and an aluminum seal.

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

Each package of Mitomicin Medac contains 1, 5 or 10vials.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr.6

22880Wedel

Germany

Phone: +4941038006-0

Fax: +4941038006-100

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Laboratorios Gebro Pharma, S.A.

Avenida Tibidabo n°29

08022Barcelona

Spain

Phone:+34 93 205 86 86

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

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

Mitomycin Medac

Spain, Italy, Portugal:

Mitomicin Medac

Slovenia

Mitomicin Medac

Last review date of this leaflet: 07/2024.

Further information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Dosage

Intravenous administration

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

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

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

Intravesical administration

There are various intravesical administration regimens for 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 40mg, instilled into the bladder once a week. Other regimens may also be used, with instillations every two weeks, every month, or every three months.

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

It is recommended to use this medicinal product at its optimal pH (urine pH>6) and to reduce the intake of liquids before, during, and after instillation. The bladder should be emptied before instillation. Mitomycin is introduced into the bladder via a catheter and at low pressure. The individual instillation time should be 1-2hours. During this time, 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 2hours, the patient should evacuate the instilled solution, preferably in a sitting position.

Reconstitution of the injectable solution or ready-to-use perfusion solution

Mitomicin 2mg

Dissolve the contents of a 2mg vial of Mitomicin Medac in 2ml of injectable water, inverting the vial.

Mitomicin 10mg

Dissolve the contents of a 10mg vial of Mitomicin Medac in 10ml of injectable water, inverting the vial.

Mitomicin 20mg

Dissolve the contents of a 20mg vial of Mitomicin Medac in 20ml of injectable water, inverting the vial.

Mitomicin 40mg

Dissolve the contents of a 40mg vial of Mitomicin Medac in 40ml of injectable water, inverting the vial.

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

Mitomicin Medac should not be used mixed with other injectables. Other injectable solutions or perfusions should be administered separately.

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

Reconstitution of the intravesical solution ready for use

Mitomicin 2mg

Dissolve the contents of 10–20vials of Mitomicin Medac 2mg (equivalent to 20‑40mg of mitomycin) in 20‑40ml of sterile injectable sodium chloride solution (0.9%)

Mitomicin 10mg

Dissolve the contents of 2–4vials of Mitomicin Medac 10mg (equivalent to 20‑40mg of mitomycin) in 20‑40ml of sterile injectable sodium chloride solution (0.9%)

Mitomicin 20mg

Dissolve the contents of 1‑2vials of Mitomicin Medac 20mg (equivalent to 20‑40mg of mitomycin) in 20‑40ml of sterile injectable sodium chloride solution (0.9%)

Mitomicin 40mg

Dissolve the contents of a vial of Mitomicin Medac 40mg (equivalent to 40mg of mitomycin) in 40ml of sterile injectable sodium chloride solution (0.9%)

The solution should be clear blue-violet and should be formed within 2minutes.

Notes

After reconstitution, the medicinal product should be used immediately.

Only clear solutions should be used. The contents of the vials are intended for single use/ administration only. Unused solutions should be discarded.