Mitomycin, 40 mg, powder and solvent for intravesical solution – patient leaflet, side effects, dosage

1. What Mitomycin is and what it is used for

Mitomycin is a medicine for the treatment of cancer, i.e. a medicine which prevents or considerably 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 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 of their growth.

Therapeutic indications

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

2. What you need to know before you use Mitomycin

Mitomycin may only be administered if strictly indicated, and by doctors experienced in this type of therapy.

Do not use Mitomycin

• if you are allergic to mitomycin or any of the other ingredients of this medicine (listed in section 6),
• while breast-feeding: you must not breast-feed during treatment with mitomycin,
• if you have a perforation of the bladder wall,
• if you suffer from an inflammation of the urinary bladder (cystitis).

Warnings and precautions

Talk to your doctor or pharmacist before using Mitomycin.

Particular caution is required when using Mitomycin

• if you are in poor general health,
• if you are suffering from impaired lung, kidney or liver function,
• if you are undergoing radiation therapy,
• if you are being treated with other cytostatics (substances which inhibit cell growth/cell division),
• if you have been told that you have bone marrow depression (your bone marrow is not able to make the blood cells that you need). It may become worse (especially in the elderly and during long-term treatment with mitomycin); infection may get worse due to low blood count and may lead to fatal conditions,
• if you are of child-bearing age as mitomycin may affect your ability to have children in the future.

If you experience abdominal pain or pain in the pelvic region that occurs straight after or weeks or months after the application of Mitomycin in the bladder inform your doctor immediately. It can be necessary that your doctor performs an abdominal sonography to clarify the cause of your pain.

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

Avoid contact with the skin and mucous membranes. Please read the general hygiene instructions after an intravesical instillation into the bladder:

It is recommended to sit down for urinating to avoid spillage of the urine and to wash hands and genital area after urinating. This applies especially to the first urination following mitomycin administration.

Children and adolescents

The use of Mitomycin in children and adolescents is not recommended.

Other medicines and Mitomycin

No interactions with other medicines are known if mitomycin is given in the bladder (intravesical administration).

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

If other forms of treatment (in particular other anti-cancer medicines, radiation) which also have a harmful effect on the bone marrow are used at the same time, it is possible that the harmful effect of mitomycin on the bone marrow will be intensified.

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

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

There are reports from animal experiments that the effect of mitomycin gets lost, if administered together with vitamin B₆.

You should not get vaccinated with live vaccines during mitomycin treatment because this may put you at an increased risk to get infected by the live vaccine.

The harmful effect on the heart of Adriamycin (doxorubicin, a medicine belonging to the group of cytostatics) can be intensified by mitomycin.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Mitomycin can cause inherited genetic damage and can adversely affect the development of an embryo. You must not become pregnant during treatment with mitomycin: If you become pregnant, genetic counselling must be provided.

You should not use mitomycin during pregnancy. Your doctor has to evaluate the benefit against the risk of harmful effects on your child, if mitomycin treatment during pregnancy is necessary.

Breast-feeding

Mitomycin probably passes into breast milk. Breast-feeding must be discontinued during treatment with Mitomycin.

Fertility/Contraception in males and females

As a sexually mature patient you must take contraceptive measures or practise sexual abstinence during chemotherapy and for 6 months afterwards.

Mitomycin can cause inherited genetic damage. As a man treated with mitomycin you are therefore advised not to father a child 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 mitomycin therapy.

Driving and using machines

Even when used in accordance with instructions this medicine may cause nausea and vomiting and thereby reduce your reaction times to such an extent that the ability to drive a motor vehicle or use machines is impaired. This applies in particular if you consume alcohol at the same time.

3. How to use Mitomycin

Mitomycin is administered by trained healthcare personnel only.

This medicine is intended to be used for introduction into the urinary bladder (intravesical instillation) after being dissolved.

Your doctor will prescribe a dose that is right for you.

Mitomycin is introduced into an empty bladder at low pressure by means of a catheter. Your healthcare professional will empty your bladder before the treatment with a catheter. Do not go to the toilet directly prior to your healthcare professional visit. The medicine should remain in the bladder for a period of 1 - 2 hours. To allow this, you should not drink too much liquid before, during and after the treatment. While the solution remains in your bladder, it should have sufficient contact with the entire mucosal surface, moving around supports the treatment. After 2 hours you should empty your bladder in a sitting position to avoid spillage.

If you use more Mitomycin than you should

If you have been accidentally given a higher dose you may experience symptoms such as fever, nausea, vomiting and blood disorders. Your doctor may give you 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 side effects

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

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

Please inform your doctor immediately if you notice any of the following reactions (which have been observed very rarely following instillation in the bladder), because mitomycin therapy will have to be stopped:

• severe allergic reaction, with symptoms such as faintness, skin rash or hives, itching, swelling of lips, face and airway with difficulty in breathing, loss of consciousness
• severe lung disease presenting as shortness of breath, dry cough and crackling sounds when breathing-in (interstitial pneumonia)
• severe renal dysfunction: kidney disease where you pass little or no urine.

Common: may affect up to 1 in 10 people

• bladder inflammation (cystitis) which may be accompanied by blood in the bladder/urine
• painful urination (dysuria)
• frequent urination at night (nocturia)
• excessive frequent urination (pollakiuria)
• blood in the urine (haematuria)
• local irritation of the bladder wall
• localised skin rash (local exanthema)
• allergic skin rash
• skin rash caused by 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 over the whole body (generalised exanthema)

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

• bladder inflammation with damage of the bladder tissue (necrotising cystitis)
• allergic (eosinophilic) bladder inflammation (cystitis)
• narrowing (stenoses) of the urinary tract

• reduced bladder capacity

  • calcium deposits in the bladder wall (bladder wall calcification)
  • partial conversion of bladder wall tissue into connective tissue (bladder wall fibrosis)
  • decreased number of white blood cells (leukopenia) increasing the risk of infections
  • decreased number of platelets (thrombopenia) causing bruises and bleeding
  • systemic allergic reactions
  • lung disorder presenting as shortness of breath, dry cough and crackling sounds when breathing-in (interstitial lung disease)
  • increased levels of liver enzymes (transaminases increased)
  • hair loss (alopecia)
  • feeling sick (nausea) and being sick (vomiting)
  • diarrhoea
  • kidney disease (renal dysfunction) where you pass little or no urine
  • fever

Not known: frequency cannot be estimated from the available data

If mitomycin reaches other regions than the bladder by accident:

• bladder damage
• pocket of pus in the abdomen (abscess)
• death of (fat) tissue (necrocis) of the surrounding area
• vesical fistula

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

Very common: may affect more than 1 in 10 people

• inhibition of blood cell production in the bone marrow (bone marrow suppression)
• decreased number of white blood cells (leukopenia) increasing the risk of infections
• decreased number of platelets (thrombopenia) causing bruises and bleeding
• feeling sick (nausea) and being sick (vomiting)

Common: may affect up to 1 in 10 people

• lung disorder presenting as shortness of breath, dry cough and crackling sounds when breathing-in (interstitial pneumonia)
• difficulties breathing (dyspnoea), 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 palms and soles (palmar-plantar erythema)
• kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased levels of creatinine in the blood) where you pass little or no urine

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

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

Uncommon: may affect up to 1 in 100 people

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

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

• life-threatening infection
• blood poisoning (sepsis)
• decrease in number of red blood cells due to an abnormal breakdown of these cells (haemolytic anaemia)
• bruises (purpura) and red and purple dots (petechiae) on the skin (thrombotic thrombocytopenic purpura)
• heart failure (cardiac insufficiency) after previous therapy with anti-cancer medicines (anthracyclines)
• raised blood pressure in the lungs, e.g. leading to shortness of breath, dizziness and fainting (pulmonary hypertension)
• disease involving obstruction of the 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 (icterus)
• disease involving obstruction of the veins in the liver (veno-occlusive liver disease, VOD)
• rash over the whole body (generalised exanthema)
• a particular form of kidney failure (haemolytic uraemic syndrome, HUS) characterised by destruction of red blood cells that outpaces your bone marrow’s production (haemolytic anaemia), acute kidney failure, and a low platelet count
• a type of haemolytic anaemia caused by factors in the small blood vessels (microangiopathic haemolytic anaemia, MAHA)

Not known: frequency cannot be estimated from the available data

• infection
• reduced blood cell count (anaemia)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Mitomycin

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

Do not use this medicine after the expiry date which is stated on the label and carton after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special temperature storage conditions.

Keep the vial in the outer carton in order to protect from light.

The physical and chemical in-use stability has been demonstrated for 48 hours when stored protected from light at room temperature (15 °C – 25 °C) and for 72 hours when stored protected from light at 2 °C – 8 °C in a refrigerator.

From a microbiological point of view, the medicinal product should be used immediately.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, protected from light, unless reconstitution has taken place in controlled and validated aseptic conditions. Protect the reconstituted solution from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Mitomycin contains

• The active substance is mitomycin.

  1 vial powder for solution for intravesical use contains 40 mg mitomycin. After reconstitution with 40 mL solvent 1 mL solution for intravesical use contains 1 mg mitomycin.

• The other ingredients are:

  Powder for solution for intravesical use: Urea Solvent for intravesical solution: Sodium chloride, water for injections, pH adjusting agents (1 M sodium hydroxide, 1 M hydrochloric acid).

What Mitomycin looks like and contents of the pack

Mitomycin is a grey to grey-blue powder.

The solvent is a clear and colourless solution.

Mitomycin powder and solvent for intravesical solution (instillation set) is available in packs with 1, 4 or 5 clear glass vials (50 mL) with a coated rubber stopper and aluminium seal. Instillation sets for intravesical instillation also include 1, 4 or 5 APP* bags with a volume of 40 mL containing sodium chloride 9 mg/mL (0.9 %) solution for injection. The sets are available with or without catheters and/or connectors (Luer-Lock to conical).

* APP = Advanced Polypropylene (polyolefin/ polypropylene/styrene-block copolymer)

Not all 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

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria, Belgium, Denmark, Estonia, Finland, Iceland, Ireland, Latvia, Lithuania, Netherlands, Norway, Poland, Slovak Republic, Sweden:

Mitomycin medac

Germany:

mito-extra

Italy:

Miturox

Portugal:

Mitomicina medac

Slovenia

Mitomicin medac

United Kingdom

Mitomycin

This leaflet was last revised in 01/2025.

Mitomycin, 40 mg powder and solvent for intravesical solution

70233-VB3GB

AA

Mitomycin, 40 mg powder and solvent for intravesical solution

70233-VB3GB

AA

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The following information is intended for healthcare professionals only:

Important information on the use of Mitomycin

Mitomycin may only be used by appropriately trained healthcare professionals.

Ensure suitable storage (see section 5) and the integrity of the packaging.

Therapy regimens

There are many intravesical mitomycin regimens, varying in the dose of mitomycin used, the frequency of instillation and the duration of therapy.

Unless otherwise specified, the dose of mitomycin is 40 mg instilled into the bladder once weekly. Regimens with instillations every 2 weeks, every month or 3 monthly can also be used.

The specialist should decide on the optimum regimen, frequency and duration of therapy on an individual patient basis.

It is advised to use this medicinal product at its optimal pH (urinary pH > 6). By reducing fluid intake before, during and after instillation the dilution effect on the mitomycin concentration in the urinary bladder can be reduced. The bladder must be emptied before instillation. Mitomycin is instilled into the bladder by means of a catheter and at low pressure. After the catheter has been removed, the solution should remain in the bladder for 1 – 2 hours. During this period the solution should have sufficient contact with the entire mucosal surface of the bladder. Therefore, care should be taken that the patient changes position every 15 minutes. After 2 hours the patient should void the instilled solution, preferably in a sitting position.

Basic principles and protective measures for the use of Mitomycin

In general, direct contact with Mitomycin should be avoided. Mitomycin is a cytostatic that poses a risk to people and the environment. A hazard may occur if the medicinal product is able to enter the body via injuries or through unprotected softened skin, if aerosols are inhaled, droplets get into the eyes or come into contact with mucous membranes, or if ingested. Do not eat, drink or smoke in the work areas and do not store any food, drinks or tobacco products here. It is recommended that a closed, splashproof protective gown, disposable gloves, a suitable respirator mask and safety goggles with side shields are worn as personal protective equipment during handling. Mitomycin may only be transported in closed containers (for storage conditions after reconstitution, see section 5). After working and in the case of contact with skin, wash your hands thoroughly with plenty of water and use skin care products.

Preparation of the reconstituted intravesical solution

Before use, the medicinal product must be dissolved under aseptic conditions with sterile 0.9 % (9 mg/mL) sodium chloride solution (see Instructions for Use, step 7). Dissolve the content of one vial of Mitomycin (equivalent to 40 mg mitomycin) in 40 mL sterile 0.9 % (9 mg/mL) sodium chloride solution. The content of the vial must dissolve to form a blue-purple clear solution within 2 minutes. Only clear blue-purple solutions may be used.

Use of a lubricant is recommended to minimise the risk of traumatic catheterisation and to make the procedure more comfortable. Women might need less lubricant than men. Drain the bladder after catheterisation to reduce the amount of lubricant potentially introduced before you administer Mitomycin.

The content of the vial is intended for single use/single dose only. Unused solution must be disposed of.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

For further information regarding the catheter please see the corresponding instructions for use.

Instructions for users of Mitomycin

Constituents and application of the instillation set

Main constituents of the instillation set

D

E

B

A

C

C2

C1 C4

D1

F

C3

Main constituent

Description

A Vial with powder

B Protective cover

C Solvent bag with 0.9 % (9 mg/mL)

sodium chloride solution

C1 Vial connector with protective cap and

break-open seal

C2 Luer-Lock catheter connector with

protective cap and break-open seal

C3 Pressure clamp

C4 Filling port without application function

D Luer-Lock catheter

D1 Lubricant

E Disposal bag

F Luer-Lock to conical connector

Connecting the vial to the solvent bag

1. 1.

   Lay out the disposal

   bag (E) ready for direct

   disposal of the set after

   instillation to prevent

   contamination.

2. 2.

   Remove the flip-off cap

   from the vial (A) and

   disinfect the stopper

   according to local

   regulations.

3. 3.

   Tear open the protective

   cover (B) of the solvent

   bag (C) and remove

   the protective cover

   completely.

   CC

   B

4. 4.

   Remove the protective

   cap from the vial

   connector (C1).

   C1

5. 5.

   Push the connector

   onto the vial up to

   the stop.

Mixing the powder with the solvent

1. 6.

   Bend the break-open

   seal inside the tube of

   the vial connector (C1)

   up and down multiple

   times to break the seal.

   C1

   1. 7.

      Hold the solvent bag so that the vial is below it.

      Squeeze the solvent

      bag multiple times to

      transfer enough solvent into the vial.

      Make sure that the vial is not filled completely to allow for the

      subsequent transfer

      of the solution into the

      solvent bag. Some

      solvent may remain

      inside the bag.

      Swirl the vial slowly to dissolve the medicinal

      product with the

      solvent.

      The contents of the

      vial must dissolve to

      form a blue-purple

      clear solution within

      2 minutes.

   2. 8.

      Turn the solvent bag

      upside down and hold

      it so that the vial is

      above it.

      Hold the vial.

      Squeeze the solvent

      bag multiple times until the vial is completely

      empty.

      If any powder remains

      inside the vial, repeat

      steps 7 and 8.

      From a microbiological point of view the

      medicinal product

      should be used

      immediately.

      If the medicinal

      product is not used

      immediately, please see section 5 “How to store Mitomycin”.

      Only use clear blue-

      purple solutions. The

      solution should not

      be administered at

      refrigerator temperature in order to prevent the

      patie nt from feeling the need to urinate resulting in a shortened exposure time.

Catheterisation

1. 9.

   Catheterise the patient according to local regulations and the instructions for use using the enclosed Luer-Lock catheter (D) and lubricant (D1) or another suitable catheter and lubricant.

   Empty the u rinary bladder using the catheter.

   Note for use with self-selected catheter with conical connector:

   The enclosed Luer-Lock to conical connector (F) must be used to connect the bag to a catheter with conical connector (not shown).

   To do this, the following additional steps must be carried out:

   • Remove the protective cap from the catheter connector (C2, see step 10).
   • Connect the Luer-Lock to conical connector (F) to the catheter connector (C2) of the bag.
   • Carefully connect the bag with the Luer-Lock to conical connector (F) to the patient’s permanent catheter.
   • Then proceed with step 11.

Connecting the catheter to the solvent bag

1. 10.

   Rotate a nd swirl the

   bag before connecting it.

   Do not administer the solution at refrigerator temperature.

   Remove the protective cap from the catheter connector (C2).

   Connect the patient’s Luer-Lock catheter

   (D) with the catheter

   connector (C2) of the solvent bag.

   C2

   C2

   D

   Instillation

   1. 11.

      Bend the break-open seal inside the tube of the catheter connector (C2) up and down multiple times to break the seal.

      Hold the patient’s catheter steady while doing so.

      C2

   2. 12.

      Hold the solvent bag with the vial upside down above the bag.

      Squeeze the solvent bag gently with the other hand so that the medicinal product is slowly instilled into the patient’s urinary bladder.

      Continue to squeeze until the solvent bag and the vial are empty.

   3. 13. Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation

1. 14.

   Closing the pressure clamp (C3) prevents a reflux of fluid into the catheter and minimises the risk of contamination. Alternatively, you can keep the solvent bag compressed while performing steps 15 and 16.

   C3

2. 15.

   Immediately remove the catheter carefully from the bladder without disconnecting the solvent bag from the catheter when the instillation set is emptied. After the catheter ha s been removed, the solution should remain in the bladder for 1 – 2 hours. Avoid contamination from splashing droplets.

   Note for use with self-selected catheter with conical connector: Separate the bag including the Luer-Lock to conical connector from the permanent catheter. Close the permanent catheter, for example using a catheter stopper or a clamp, to ensure that the medicinal product remains active in the bladder for the intended duration

3. 16.

   Dispose of the product according to national regulations using the disposal bag.

   The contents of the vial are intended for single use/single dose only. Any remaining solution must be disposed of.