Bleomycin 15000 IU Powder for solution for injection/infusion

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

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

• if you are allergic to bleomycin sulphate or any of the other ingredients of this medicine (listed in section 6) or to any similar anti-cancer medicine;
• if you have Ataxia telangiectasia (very rare inherited disease that leads to difficulties in coordinating your movements and the risk of infections);
• if you have an acute lung infection or severe lung impairment;
• if you have a history of lung damage (possibly) caused by bleomycin;
• during breast-feeding (see also "Pregnancy and lactation" section).

Talk to your doctor or pharmacist or nurse before you are given Bleomycin if:

• you are over 60 years of age;
• your kidneys or liver no longer function properly;
• you have or have had a lung disease;
• you had lung irradiation prior to bleomycin treatment, or if you are having radiation therapy during bleomycin treatment;
• you have chickenpox;
• you are being administered oxygen. Tell your doctor that you are using bleomycin.

Cases of cancer in the blood (acute myeloid leukaemia) and a syndrome where the bone marrow does not make enough healthy blood cells or platelets (myelodysplastic syndrome) have been reported in patients treated concomitantly with bleomycin and other cytostatics (substances which inhibit cell growth/cell division).

You must also tell your doctor if you have an operation planned as it may be necessary to adjust your treatment with bleomycin.

The patient groups specified above are more sensitive to bleomycin's harmful effects on the lungs. The doctor will probably examine you more often and/or take X-rays of your lungs. If you are treated with bleomycin, a regular lung function test should be performed, to monitor the possible adverse effects of bleomycin on the lungs.

If you have a cough and/or are short of breath, this can be a sign of the adverse effects of bleomycin on the lungs. In this case you should inform a doctor immediately.

Like other cytotoxic active substances, bleomycin can trigger tumour lysis syndrome in patients with rapidly growing tumours. Appropriate supportive treatment and pharmacological measures might prevent or alleviate such complications.

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

An interaction is taken to refer to when (medicinal) products used together may influence each other's efficacy and/or side effects. An interaction may occur when bleomycin is used together with:

• Carmustine, mitomycin, cyclophosphamide, gemcitabine (medicines used for certain types of cancer) and methotrexate (a medicine used for certain types of cancer, rheumatism and severe skin diseases): there is an increased risk of harmful effects on the lungs;
• Cisplatin (an anti-cancer medicine) and other medicines that cause kidney damage: there is an increased risk of side effects from bleomycin (potentiation of pulmonary toxicity);
• Vinca alkaloids (a group of medicinal products used for certain types of cancer, e.g. vincristine, vinblastine): circulatory disturbances may occur in the extremities (fingers, toes, tip of the nose). In very severe cases the extremities can die (necrosis);
• Acetyldigoxin (a medicine for cardiac disorders): there is a risk that the effect of acetyldigoxin will be reduced;
• Phenytoin (a medicine for epilepsy): there is a risk that the effect of phenytoin will be reduced;
• Clozapine (a medicine for schizophrenia): it may cause more severe reduction in number of white blood cells which makes infections more likely;
• Radiotherapy: the risk of side effects on the lungs and/or mucous membranes is increased;
• Oxygen: you are at greater risk of pulmonary toxicity if you are given oxygen during anaesthesia;
• Gentamicin, amikacin and ticarcillin (medicines that inhibit the growth of bacteria): the efficacy of these substances may be reduced;
• Ciclosporine and tacrolimus (medicines that reduce efficacy of immune system): risk of excessive generation of lymphocytes;
• Granulocyte colony-stimulating factor: lung damage may be aggravated;
• Live vaccines: there is a risk of serious or life-threatening infections caused by the vaccine. Vaccinations with live vaccines should therefore not be administered to patients receiving bleomycin.

Pregnancy

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 using this medicine.

Animal studies have shown that this medicine can harm the embryo.

The use of bleomycin should be avoided during pregnancy, especially during the first 3 months.

If bleomycin treatment is vital during the first three months of pregnancy, a medical consultation on aborting the pregnancy is essential.

Both men and women must take measures to prevent a pregnancy during use of bleomycin, and for 6 months after the end of the treatment. If pregnancy occurs during treatment with bleomycin, genetic counselling is recommended.

Men who wish to father children in the future should seek advice on storing sperm before starting treatment with bleomycin because there is possibility of becoming irreversibly infertile by the treatment.

Breast feeding

It is not known whether bleomycin or the metabolically degraded materials are secreted in your milk, but since there is a possibility that bleomycin is harmful to your child, you must not breast-feed during treatment with bleomycin.

Fertility

Bleomycin therapy may cause irreversible infertility.

This medicinal product may affect your reactions and your ability to drive.

Possible side effects of chemotherapy with bleomycin may occur, such as nausea and vomiting. If you are affected by these side effects, you should not drive and/or operate machines that require you to be alert.

Symptoms that can occur if you have received too much Bleomycin include: low blood pressure, fever, increased heart rate and shock. If you notice any of the above symptoms, please tell your doctor, who will arrange for the appropriate treatment. Use of the medicinal product must be discontinued immediately.

If you have missed an injection, please talk with your treating doctor, to clarify if and how to make up for the missed dose.

If you suddenly stop taking Bleomycin without consulting a doctor, the original symptoms may recur.

If you develop any of the following side effects, tell your doctor immediately:

• coughing
• breathlessness
• cracking or popping sound when breathing

You may need to have your treatment stopped.

Side effects can include the following:

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

• interstitial pneumonitis (inflammatory changes in the lungs)
• pulmonary fibrosis (disease of the lung tissue caused by increased formation of connective tissue between the alveoli)
• laboured breathing
• loss of appetite
• weight loss
• nausea and vomiting
• mucositis (inflammation of the mucous membranes)
• stomatitis (inflammation of the mucous lining of the mouth)
• inflammatory redness of the skin
• itching
• striae (stretch marks)
• blistering
• hyperpigmentation (increased pigment formation)
• tenderness and swelling of the fingertips
• hyperkeratosis (excessive thickening of the skin)
• hair loss

Common (may affect up to 1 in 10 people)

• severe hypersensitivity reactions. These reactions may occur immediately, or after a delayed period of a few hours after the first or second dose. Tell your doctor straight away if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body). idiosyncratic reaction (various types of hypersensitivity reaction)
• headache
• acute respiratory insufficiency (acute respiratory distress syndrome - ARDS)
• respiratory failure
• pulmonary embolism
• rash, urticaria, erythema
• induration (hardening of the skin)
• swelling (due to fluid retention in the tissues)
• inflammatory skin reaction
• pyrexia, chills and malaise

Uncommon (may affect up to 1 in 100 people)

• myelosuppression (damage to the bone marrow)
• leukopaenia (reduction in white blood cell count)
• neutropaenia (reduction in neutrophil granulocytes in the blood)
• thrombocytopaenia (reduction in platelets)
• haemorrhage (bleeding)
• dizziness
• confusion
• low blood pressure
• angular cheilitis (infection of the corners of the mouth) and diarrhoea
• deformation and discolouration of the nails, bulla formation at pressure points
• muscle and joint pain
• oliguria (decreased urine output)
• pain during urination
• polyuria (increased urine output)
• urinary retention
• pain in the tumour area
• phlebitis (inflammation of a vein)
• hypertrophy (thickening) of the vein wall and venous access constriction (with i.v. administration)
• induration (hardening of the tissue following administration into a muscle or with local administration)

Rare (may affect up to 1 in 1000 people)

• neutropaenic fever (fever caused by a decrease in white blood cells)
• heart attack, pericarditis (inflammation of the fibrous sac surrounding the heart) and chest pain
• cerebral infection, thrombotic microangiopathy (disease of the capillaries and arterioles), haemolytic uraemic syndrome (severe disease affecting the blood and kidneys)
• cerebral arteritis (inflammation of the small and medium-sized arteries in the brain)
• Raynaud's phenomenon (a vascular disorder), arterial thrombosis, deep vein thrombosis
• hepatic impairment
• scleroderma (hardening of the connective tissue)

Vary rare (may affect up to 1 in 10,000 people)

• tumour lysis syndrome (condition following rapid breakdown of tumours)

Not Known (frequency cannot be estimated from the available data)

• overwhelming infection (sepsis)
• severe reduction in blood cells (pancytopenia)
• reduction in red blood cells (anaemia)

If you get any side effects, talk to your doctor or hospital 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 Website: 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 bleomycin (as bleomycin sulphate).
  Each vial contains 15,000 International Units (I.U.) of bleomycin (as bleomycin sulphate).
• There are no other ingredients.

White freeze dried substance in type-I clear glass vial closed with a bromobutyl rubber stopper and sealed with a flip-off aluminium seal.

Pack of 1 vial.

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