Mitomycin medac, 40 mg, Powder and solvent for intravesical solution

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

Mitomycin medac 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).

• 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).

Talk to your doctor or pharmacist before using Mitomycin medac.

Particular caution is required when using Mitomycin medac

• 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 medac 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.

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

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.

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 medac.

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.

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.

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.

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

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)

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.

• 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).

Mitomycin medac is a grey to grey-blue powder.

The solvent is a clear and colourless solution.

Mitomycin medac 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.