Package leaflet: Information for the user

Mitomycin 40mg powder for solution for injection/infusion

Mitomycin

What is in this leaflet:-

1.    What Mitomycin is and what it is used for

2.    What you need to know before you use Mitomycin

3.    How to use Mitomycin

4. Possible side effects

5. How to store Mitomycin

6.    Contents of the pack and other information.

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. The therapeutic application of medicinal products for the treatment of cancer 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 used in cancer therapy for the relief of symptoms (palliative cancer therapy). Intravenous application

When administered intravenously it is used in monochemotherapy, i.e. treatment with only one active substance, or in combined cytostatic chemotherapy, i.e. treatment with several active substances. Mitomycin is effective in the case of the following tumours:

•    advanced metastatic stomach cancer (stomach carcinoma)

•    advanced and/or metastatic breast cancer (breast carcinoma)

•    cancer of the respiratory tract (non-small cell bronchial carcinoma)

•    advanced cancer of the pancreas (pancreatic carcinoma)

2.    What you need to know before you use Mitomycin Mitomycin must not be administered:

-    if you are hypersensitive (allergic) to mitomycin or any of the other constituents of Mitomycin .

-    during breastfeeding

if you suffer from a major reduction in the number of all types of blood cells (including red and white blood cells as well as platelets [pancytopenia]), or an isolated reduction of white blood cells (leucopenia) or blood platelets (thrombocytopenia), a tendency to bleeding (haemorrhagic diathesis) or acute infections (disease caused by pathogens).

Warnings and precautions

Talk to your doctor or pharmacist before using Mitomycin

-    if you are suffering from impaired lung, kidney or liver function.

-    if your general state of health is not good

-    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 be worse (especially in the elderly and during long term treatment with mitomycin); infection may be aggravated due to bone marrow depression and may lead to fatal conditions.

-    if you are capable to have a baby as mitomycin may affect your ability to have children in the future.

You will be given the treatment under the supervision of a healthcare professional who is experienced in this particular branch of medicine to minimise any unwanted side effects in the injection site.

Children and adolescents

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

Other medicines and Mitomycin

Tell your doctor or pharmacist if you are taking/using, have recently taken/used or might take/use any other medicines.

Through the additional use of other types of therapy (in particular other anti-cancer medicines, radiation) which also have harmful effects on you, it is possible that the adverse effects of mitomycin will be reinforced.

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

You should not get vaccinated, especially with live vaccines during mitomycin treatment.

Please note that the above also applies to medications used in the recent past.

Pregnancy, breast-feeding and fertility

Mitomycin should not be used 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.

Women of child-bearing age should avoid becoming pregnant. Contraceptive measures must be taken by both male and female patients during and for at least six months after cessation of therapy. Still, if you become pregnant during this period you must immediately inform your doctor.

Breast-feeding must be discontinued before you start to use mitomycin.

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 operate machinery is impaired. This applies in particular in conjunction with alcohol.

3.    How to use Mitomycin

Mitomycin should only be administered by healthcare professionals experienced in this kind of therapy.

Mitomycin is intended to be used for injection or infusion into a blood vessel (intravenous use) after being dissolved.

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

Before you receive mitomycin as injection or infusion into a vein a blood test, check of lung, kidney and liver function is recommended to exclude any diseases, which could worsen during mitomycin therapy.

The needle must remain in the vein while mitomycin is being given. If the needle comes out or becomes loose, or the medicinal product is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.

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, please 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 administration into a vein

Severe lung disease presenting as shortness of breath, dry cough and crackles during breath-in

(interstitial pneumonia) as well as severe renal dysfunction (nephrotoxicity) may occur. If you

notice any of the above reactions please inform your doctor immediately because mitomycin

therapy must be stopped.

Very common side effects (may affect more than 1 in 10 people)

•    Blood disorders: Inhibition of blood cell production in the bone marrow; decreased number of white blood cells (leucopenia) increasing the risk of infections; decreased number of platelets (thrombocytopenia) causing bruises and bleedings

•    Nausea, vomiting

Common side effects (may affect up to 1 in 10 people)

•    Lung disorders presenting as shortness of breath, dry cough and inspiratory crackles (interstitial pneumonia)

•    Dyspnoea, cough, shortness of breath

•    Skin rashes and irritation of the skin

•    Numbness, swelling and painful redness on palms and soles (palmar-plantar erythema)

•    Kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased levels of creatinine in the blood) - the kidneys may not be able to work

•    Inflammation of connective tissue (cellulitis) and death of tissue (tissue necrosis) following accidental injection into the surrounding tissue (extravasation)

Uncommon side effects (may affect up to 1 in 100 people)

•    Inflammation of a mucous membrane (mucositis)

•    Inflammation of the mucosa of the mouth (stomatitis)

•    Diarrhoea

•    Hair loss (alopecia)

•    Fever

•    Loss of appetite (anorexia)

Rare side effects (may affect up to 1 in 1,000 people)

•    Life-threatening infection

•    Blood poisoning (sepsis)

•    Decrease in number of red blood cells sometimes together with a acute renal dysfunction (haemolytic anaemia, microangiopathic-haemolytic anaemia (MAHA syndrome), Haemolytic uraemic syndrome (HUS))

•    Loss of cardiac function (heart failure) after previous therapy with other anti-cancer medicines (anthracyclines)

•    Increase in blood pressure in the vasculature of the lungs, e,g, leading to shortness of breath, dizziness and fainting (pulmonary hypertension)

•    Obstructive disease of the pulmonary veins (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)

•    Blockage of the small veins in the liver (veno-occlusive disease [VOD] of the liver) leading to fluid retention, increased liver size and raised levels of bilirubin in the blood

•    Widespread skin rash

Very rare side effects (may affect up to 1 in 10,000 people)

• Severe allergic reaction (symptoms may include faintness, skin rash or hives, itching, swelling of lips, face and airway with difficulty in breathing, loss of consciousness)

If you get any side effects talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

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 agency’s website: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Mitomycin

Do not refrigerate or freeze.

Reconstituted solution: Chemical and physical in-use stability has been demonstrated in the recommended diluents for 24 hours stored at 25°C and 2-8°C.

Diluted solution: After dilution, the solution should be used immediately

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 folding box after “EXP”. The expiry date refers to the last day of that month.

Do not throw away any medicine via waste water or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to 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 injection/infusion contains 40 mg mitomycin. After reconstitution with 80 ml water for injections each ml solution contains 0.5 mg mitomycin.

The other ingredient is Mannitol (E421)

What Mitomycin looks like and contents of the pack

Mitomycin is a powder which is mixed before injection. It is packaged in an amber coloured glass vials with a rubber stopper and aluminium seal.

Mitomycin is available in packs contains 1, 5 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Mylan

Potters Bar

Hertfordshire

EN6 1TL

United Kingdom

Manufacturer

Agila Specialties Polska Sp. z. o. o.

10, Daniszewska Str., 03-230 Warsaw Poland

The leaflet was last revised on 10/2014

The following information is intended for medical or healthcare professionals only:

General Information

It is essential that the injection is administered intravenous. If the medicinal product is injected perivasally, extensive necrosis occurs in the area concerned. To avoid necrosis following recommendations apply:

•    Always inject into large veins in the arms.

•    Do not directly inject intravenously, but rather into the tube of a good and securely running infusion.

•    Before removing the cannula after central venous administration, flush it through for a few minutes using the infusion in order to release any residual mitomycin.

If extravasation occurs, it is recommended that the area is immediately infiltrated with sodium bicarbonate 8.4% solution, followed by an injection of 4 mg dexamethasone. A systemic injection of 200 mg of Vitamin B6 may be of some value in promoting the regrowth of tissues that have been damaged.

Contacts with the skin and mucous membranes must be avoided.

Method of administration

Mitomycin is intended for intravenous injection or infusion after being dissolved. Partial use is applicable.

Special precautions for disposal and other handling

Preparation of ready-to-use solution for injection or infusion

The contents of the vial should be reconstituted with water for injection or 0.9% sodium chloride injection, to a concentration of 0.5mg/ml.

Preparation of Reconstituted solution

The contents of one vial of Mitomycin 40 mg are dissolved in 80 ml of water for injections or 0.9% sodium chloride solution. After reconstitution with 80 ml solvent each ml of solution contains 0.5 mg mitomycin.

If the powder does not dissolve immediately, allow it to stand at room temperature until it has completely dissolved. The contents of the vial must dissolve to form a clear solution within 2 minutes.

For intravenous infusion the solution of Mitomycin 40 mg is further diluted with 0.9% sodium chloride solution or Sodium Lactate Injection to a concentration of 20 or 40 micrograms of mitomycin/ml.

Notes

•    Mitomycin 40 mg must not be used in mixed injections.

•    Other injection solutions or infusion solutions must be administered separately.

•    It is essential that the injection is administered intravenous.

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

Diluted solution: After dilution, the solution should be used immediately