Mitomycin Medac

Package leaflet: Information for the user

Mitomicina medac 1 mg/ml, powder for injectable/infusion solution or for

intravesical use
mitomycin
Generic medicine
Please read all of this leaflet carefully before 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 side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this 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 side 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 significantly slows down the division of actively dividing cells by affecting their metabolism in various ways (cytostatic agent). The therapeutic use of cytostatic agents in cancer therapy is based on the fact that one of the differences between cancer cells and normal cells in the body is the faster rate of cell division in cancer cells, as their growth cannot be controlled.

Therapeutic indications

Mitomicina medac is used in oncology to relieve symptoms (palliative oncology therapy).

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 cancers:

• 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 cancers

Intravesical administration

This medicine is introduced into the urinary bladder (intravesical administration) to prevent recurrence of superficial bladder cancer following removal of the cancerous tissue via the urethra (transurethral resection).

2. What you need to know before using Mitomicina medac

Mitomicina medac may only be administered when strictly indicated, under continuous monitoring of blood counts when given intravenously, and by physicians experienced in this type of therapy.

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 while being treated with mitomycin
• in case of intravenous administration (injection or infusion into a blood vessel):
• if you have a significant reduction in the number of all blood cells (red blood cells, white blood cells, and platelets [pancytopenia]) or a reduction in white blood cells alone (leukopenia) or platelets alone (thrombocytopenia)
• if you have a tendency to bleed (hemorrhagic diathesis)
• if you have acute infections (disease caused by pathogens)
• in case of intravesical administration (application into the bladder):
• if you have a perforation of the bladder wall
• if you suffer from inflammation of the bladder (cystitis).

Warnings and precautions

Talk to your doctor or pharmacist before using Mitomicina medac.

Special caution is required when using Mitomicina medac

• if you are in poor general health
• if you have impaired lung, kidney, or liver 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 told that you have bone marrow depression (your bone marrow is unable to produce the blood cells you need). This condition may worsen (especially in elderly patients and during long-term treatment with mitomycin); infections may worsen due to low blood cell counts and could be fatal
• if you are of childbearing age, as mitomycin may impair your ability to have children in the future.

Mitomycin is a substance that may cause significant heritable genetic alterations and has the potential to cause cancer in humans.

Intravesical administration

Inform your doctor immediately if you experience abdominal or pelvic pain shortly after the instillation of Mitomicina medac into the bladder, or even weeks or months later. Your doctor may need to perform an abdominal ultrasound to determine the cause of the pain.

Avoid contact with skin and mucous membranes.

Read the general hygiene instructions to follow after intravesical instillation:

It is recommended to urinate while sitting down to avoid splashing of urine, and to wash your hands and genital area after urination. This is particularly important the first time you urinate after mitomycin administration.

Children and adolescents

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

Other medicines and Mitomicina medac

No interactions with other medicines are known in the case of intravesical administration of mitomycin.

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

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

When administered concomitantly with other treatments (particularly other anticancer medicines, radiotherapy), which also have a toxic effect on the bone marrow, the bone marrow toxicity of Mitomicina medac may be intensified.

Combination with vinca alkaloids or bleomycin (medicines belonging to the group of cytostatics) may increase the severity of lung toxicity.

In patients treated with intravenous mitomycin concomitantly with 5-fluorouracil or tamoxifen, an increased risk of a specific kidney disease (hemolytic-uremic syndrome) has been observed.

Animal experiments have shown a loss of mitomycin effect when administered together with vitamin B_.

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

Mitomycin may increase the severity of the cardiotoxic effect of Adriamycin (doxorubicin, a medicine belonging to the group of cytostatics).

Pregnancy, breastfeeding, and fertility

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy

Mitomycin may cause heritable genetic alterations and adverse effects on embryonic development. You must avoid pregnancy during treatment with mitomycin. In case of pregnancy, genetic counseling should be provided.

You must not use mitomycin during pregnancy. Your doctor must evaluate the benefit versus the risk of harmful effects on the unborn child if treatment with mitomycin becomes necessary during pregnancy.

Breastfeeding

Mitomycin is probably excreted in breast milk. Breastfeeding must be discontinued during treatment with Mitomicina medac.

Fertility/Contraception in men and women

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

Mitomycin may cause heritable genetic alterations. If you are a man undergoing mitomycin therapy, you must not father children during treatment and for 6 months after treatment ends, and you should seek advice on sperm preservation before starting therapy, as mitomycin may cause irreversible infertility.

Driving and using machines

Even when used according to instructions, this medicine may cause nausea and vomiting, thereby prolonging reaction times to an extent that may impair your ability to drive vehicles or operate machinery. This is particularly relevant if alcohol is used concomitantly.

3. How to use Mitomycin medac

Mitomycin medac is administered only by trained healthcare professionals.
This medicinal product is intended for administration by injection or infusion into a blood vessel
(intravenous use) or instillation into the urinary bladder (intravesical instillation) after dissolution.
Your doctor will prescribe a dose and treatment schedule suitable for you.
Intravenous administration
Before receiving Mitomycin medac by injection or infusion, a blood test and assessment of lung, kidney, and liver function are recommended to rule out pre-existing conditions that may worsen during mitomycin therapy.
During administration of Mitomycin medac, the needle must remain properly positioned in the blood vessel. If the needle becomes dislodged or loosens, or if the medicine leaks into the surrounding tissue (in which case 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 must empty your bladder before treatment. The medicine must remain in the bladder for a period of 1 to 2 hours. For this reason, you should avoid drinking excessive fluids before, during, and after treatment. While the solution remains in the bladder, ensure adequate contact with the entire mucosal surface; moving around may help enhance treatment effectiveness. After 2 hours, you should empty your bladder while sitting down to avoid urine splashing.
If you use more Mitomycin 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 prescribe supportive therapy to manage any symptoms that may occur.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Possible side effects following injection or infusion into a blood vessel (intravenous administration)

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

A severe lung disease may develop, characterized by shortness of breath, dry cough and crackling sounds during inspiration (interstitial pneumonia), and severe kidney dysfunction (kidney disease with reduced or no urine output).

If you notice any of these reactions, 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 (bone marrow suppression)
• Reduction in the number of white blood cells (leucopenia), leading to increased risk of infection
• Reduction in the number of platelets (thrombocytopenia), causing bruising and bleeding
• Nausea and vomiting

Common: may affect up to 1 in 10 people

• Lung disorder characterized by shortness of breath, dry cough and crackling sounds during inspiration (interstitial pneumonia)
• Breathing difficulties (dyspnea), cough, shortness of breath
• Skin rash (exanthema)
• Allergic skin rash
• Skin rash caused by contact with mitomycin (contact dermatitis)
• Numbness, swelling and painful redness of the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia)
• Kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased blood creatinine levels), with reduced or absent urination

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
• Blood poisoning (sepsis)
• Reduction in the number of red blood cells due to abnormal destruction of these cells (haemolytic anaemia)
• Bruising (purpura) and red or purple spots (petechiae) on the skin (thrombotic thrombocytopenic purpura)
• Heart failure following previous treatment with anti-cancer medicines (anthracyclines)
• Increased blood pressure in the lungs, causing, for example, shortness of breath, dizziness and fainting (pulmonary hypertension)
• Disease with blockage of veins in the lungs (pulmonary veno-occlusive disease, PVOD)
• Liver disease (liver dysfunction)
• Increased levels of liver enzymes (transaminases)
• Yellowing of the skin and whites of the eyes (jaundice)
• Disease with blockage of veins in the liver (hepatic veno-occlusive disease, VOD)
• Skin rash all over the body (generalised exanthema)
• A specific type of kidney failure (haemolytic uraemic syndrome, HUS), characterised by destruction of red blood cells at a faster rate than their production by the bone marrow (haemolytic anaemia), acute kidney failure and low platelet count
• A form of haemolytic anaemia caused by certain factors in small blood vessels (microangiopathic haemolytic anaemia, MAHA)

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

• Severe allergic reaction (with symptoms such as fainting, skin rash or hives, itching, swelling of lips, face and airways with breathing difficulties, loss of consciousness)

Not known: frequency cannot be estimated from the available data

• Infections
• Reduction in the number of blood cells (anaemia)

Possible side effects following instillation into the bladder (intravesical use)

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

• Severe allergic reaction with symptoms such as feeling unwell, skin rash or hives, itching, swelling of lips, face and airways with breathing difficulties, loss of consciousness,
• Severe lung disease characterised by shortness of breath, dry cough and crackling sounds during inspiration (interstitial pneumonia),
• Severe kidney dysfunction: kidney disease with reduced 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/urine
• Painful urination (dysuria)
• Frequent urination during the night (nocturia)
• Excessive frequency of urination (pollakiuria)
• Blood in the urine (haematuria)
• Local irritation of the bladder wall
• Localised skin rash (localised exanthema)
• Allergic skin rash
• Skin rash caused by contact with mitomycin (contact dermatitis)
• Numbness, swelling and painful redness of the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia)

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

• Skin rash all over the body (generalised exanthema)

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

• Inflammation of the bladder with damage to bladder tissue (necrotising cystitis)
• Allergic-type (eosinophilic) inflammation of the bladder (cystitis)
• Narrowing (stenosis) of the urinary tract
• Reduced bladder capacity
• Calcium deposits in the bladder wall (bladder wall calcification)
• Partial transformation of bladder wall tissue into connective tissue (bladder wall fibrosis)
• Reduction in the number of white blood cells (leucopenia), leading to increased risk of infection
• Reduction in the number of platelets (thrombocytopenia), causing bruising and bleeding
• Systemic allergic reactions
• Lung disorder characterised by shortness of breath, dry cough and crackling sounds during inspiration (interstitial lung disease)
• Increased levels of liver enzymes (elevated transaminases)
• Hair loss (alopecia)
• Nausea and vomiting
• Diarrhoea
• Kidney disease (renal dysfunction) with reduced or no urine output
• Fever

Not known: frequency cannot be estimated from the available data
If mitomycin accidentally reaches areas other than the bladder:

• Bladder damage
• Collection of pus in the abdomen (abscess)
• Death (necrosis) of surrounding tissue (adipose tissue)
• Bladder fistula

Reporting of side effects

If you get any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mitomicina medac

Keep this medicine out of the sight and reach of children.
Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the label and the carton after Exp.
The expiry date refers to the last day of that month.
After reconstitution, this medicine must be used immediately.
Protect the reconstituted solution from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Mitomicina medac contains

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

One vial contains 2 mg (10 mg, 20 mg, 40 mg) of mitomycin.
Description of the appearance of Mitomicina medac and package contents
Mitomicina medac is a powder for solution for injection or for infusion or for solution for intravesical use, grey to grey-blue in colour, contained in a vial with a coated rubber stopper and an aluminium seal.
Each vial contains 2, 10, 20 or 40 mg of mitomycin.
Each package of Mitomicina medac contains 1, 5 or 10 vials.
Not all pack 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
This medicinal product is authorized in the European Economic Area countries under the
following names:
Austria, Belgium, Denmark, Estonia, Finland, Germany, Iceland, Latvia, Lithuania, Norway,
Poland, Czech Republic, Slovakia, Spain:
Mitomycin medac
Italy, Portugal:
Mitomicina medac
Slovenia:
Mitomicin medac

The following information is intended for healthcare professionals only:

Dosing
Intravenous administration
In monotherapy cytostatic treatment, mitomycin is generally administered intravenously
by bolus injection.
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 regimen used.
In combination therapy, the dose is considerably lower. Due to the risk of additive myelotoxicity,
deviation from established treatment protocols should not occur without a specific reason.

Intravesical administration
There are several mitomycin-based regimens for intravesical use, differing in mitomycin dose,
frequency of instillation, and duration of therapy.
Unless otherwise specified, the mitomycin dose is 40 mg instilled into the bladder once weekly.
Regimens with instillation every 2 weeks, monthly, or every 3 months may also be used.
The specialist must determine the optimal regimen, frequency, and duration of therapy based on the 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 must be emptied prior to instillation. Mitomycin is introduced into the bladder via a catheter under low pressure. The duration of a single instillation should be 1–2 hours. During this period, the solution must be in sufficient contact with the entire bladder mucosal surface. Therefore, the patient should be mobilized as much as possible. After 2 hours, the patient should void the instilled solution, preferably while sitting.

Reconstitution of injectable or infusion solution ready for use
Mitomycin 2 mg
Dissolve the contents of one 2 mg Mitomycin medac vial in 2 ml of water for injectable preparations by inverting the vial.
Mitomycin 10 mg
Dissolve the contents of one 10 mg Mitomycin medac vial in 10 ml of water for injectable preparations by inverting the vial.
Mitomycin 20 mg
Dissolve the contents of one 20 mg Mitomycin medac vial in 20 ml of water for injectable preparations by inverting the vial.
If the powder does not dissolve immediately, allow it to stand at room temperature until complete dissolution. The vial contents should dissolve to form a clear, blue-violet solution within 2 minutes.
Mitomycin medac must not be mixed with other injections. Other injectable or infusion solutions must be administered separately.
In case of intravenous administration, extravasation must be strictly avoided.

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

Notes
After reconstitution, the medicinal product must be used immediately.
Use only clear solutions. Vial contents are for single use only and intended for a single administration. Unused solution must be discarded.