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Active substance(s): BLEOMYCIN SULPHATE

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Package leaflet: Information for the patient

Bleomycin 15000 IU Powder for solution for injection/ infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information
for you.
- 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 or hospital pharmacist or nurse. This includes any possible side effects
not listed in this leaflet. See section 4.
What is in this leaflet
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

1. What Bleomycin is and what it is used for
This medicine contains the active ingredient bleomycin sulphate. Bleomycin is one of a group of medicines called
cytostatic medicines. These medicines are anti-cancer medicines sometimes referred to as chemotherapy. They attack
cancer cells and prevent them from dividing.
Bleomycin is used to treat:
• Certain types of cancer (squamous cell carcinomas) in the head and neck, cervix and external genitalia;
• Certain types of lymph node cancer (e.g. Hodgkin's disease and Non-Hodgkin’s lymphoma of intermediate and high
• Testicular cancer;
• Fluid accumulation in the lungs (as a result of cancer).
Bleomycin can be used alone, or in combination with other cancer medications, and/or in combination with

2. What you need to know before you are given Bleomycin
Bleomycin will not be given:
- if you are allergic to bleomycin sulphate 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).
Warnings and precautions
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
- you have chickenpox
- you are being administered oxygen. Tell your doctor that you are using bleomycin
You must also tell your doctor if you have an operation planned as it may be necessary to adjust your treatment with
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
Other medicines and Bleomycin
Tell your doctor or pharmacist if you are taking or using, have recently taken or used, or might take or use any other
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
- 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, 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 using this medicine.

The following information is intended for medical professionals only:
Posology and method of administration
Bleomycin is administered parenterally as an intramuscular injection, intravenous injection/infusion, intra-arterial
injection/infusion, subcutaneous injection, intratumoural injection, or intrapleural instillation.
1) Squamous cell carcinoma
Intramuscular or intravenous injection of 10-15 x 103 IU/m2 body surface area (BSA), once or twice a week at
intervals of 3-4 weeks up to a total cumulative dose 400 x 103 IU. Intravenous infusion of 10-15 x 103 IU/m2/day for
6-24 hours on 4 to 7 consecutive days, at intervals of 3-4 weeks.
2) Hodgkin's disease and non-Hodgkin's lymphoma
When used alone, intramuscular or intravenous injection of 5-15 x 103 IU/m2 BSA, once or twice a week, up to a
cumulative dose of 225 x 103 IU. Because of the possibility of anaphylactoid reactions, lymphoma patients should
be treated with lower doses (for instance 2 x103 IU) for the first two applications. If there are no acute reactions
after 4 hours of observation the normal dose schedule can be followed.
3) Testicular tumours
Intramuscular or intravenous injection of 10-15 x 103 IU/m2 BSA once or twice a week, at intervals of 3-4 weeks up
to a total cumulative dose of 400 x 103 IU.
The intravenous infusion of the dose of 10-15 x 103 IU/m2 BSA/day is performed for 6-24 hours on 5-6 consecutive
days, at intervals of 3-4 weeks.
4) Malignant pleural effusions
60 x 103 IU in 100 mL physiological saline solution intrapleurally, as a single dose, which can be repeated after 2-4
weeks, depending on the response.
Since approximately 45 % of bleomycin is absorbed, this should be taken into account for the total cumulative dose
(body surface area, kidney function and lung function).
The development of stomatitis is the most useful guide to the determination of individual tolerance with respect to
the maximum dose. A total cumulative dose of 400 x 103 IU (corresponding to 225 x 103 IU/m2 BSA) should not be
exceeded in patients under 60, because of the increased risk of pulmonary toxicity in all indications. In lymphoma
patients, the total dose should not be more than 225 x 103 IU.
In cases of Hodgkin's disease and testicular tumours, improvement occurs rapidly and can be observed within two
weeks. If no improvement is observed by then, an improvement is unlikely. Squamous cell carcinomas respond
more slowly. In some cases it can take up to three weeks before an improvement is noted.
Elderly patients (from the age of 60)
The total dose of bleomycin in elderly patients should be reduced according to the following table:

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 3 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.
Bleomycin therapy may cause irreversible infertility.
Driving and using machines
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.
Bleomycin Powder for solution for injection/infusion contains sodium
This medicines contains less than 1 mmol sodium (23 mg) per dose, i.e essentially “sodium free”

3. How to use Bleomycin
The doctor will calculate the required quantity for you, based on the dosage details specified later.
The usual dose:
The (total) dose depends on the indication, your age, renal function, and combination with other anticancer medicines.
Your doctor will set the dose of bleomycin, the duration of the treatment, and the number of treatments. These can vary
for each patient.
There is a risk of serious hypersensitivity reaction especially in lymphoma patients which may occur directly or
sometime after administration. Therefore, your doctor will give you a test dose and will observe for 4 hours before
starting bleomycin therapy for the first time.
Method of administration
Your doctor will administer bleomycin into a vein or artery, under the skin, into a muscle, directly into the tumour, or into
the space surrounding the lungs (intrepleural), either by injection or using an infusion.
Use in children and adolescents
There is insufficient experience with regard to the administration of bleomycin in children and adolescents.
Until more information is available, bleomycin should only be administered in children and adolescents in exceptional
circumstances and at special facilities.
If you have been given more Bleomycin than you should
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.
Information for the doctor:
Information about treating an overdose can be found at the end of this leaflet.
If you have not received Bleomycin when you should
If you have missed an injection, please talk with your treating doctor, to clarify if and how to make up for the missed
If you stop taking Bleomycin
If you suddenly stop taking Bleomycin without consulting a doctor, the original symptoms may recur.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse.

4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Bleomycin can cause immediate and delayed side effects. Fever on the day of injection is the earliest reaction. Loss of
appetite, loss of hair, chills, fatigue, inflammation of the lungs (interstitial pneumonia) – shortness of breath or cough,
inflammation of the mucous lining of the mouth and nausea may also occur. Pain at the injection site and in the tumour
area has also been observed on occasion. Other sporadic side effects include a fall in blood pressure and local
thrombophlebitis (inflammation of a vein) after administration into a vein.
Skin and mucosal lesions are the most common side effects and are observed in up to 50 % of the patients treated.
They comprise redness; rash; itching; formation of ulcers, stretch marks and blisters; heavy pigmentation; and
tenderness and swelling of the fingertips.
Serious side effects:
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 patients)
• interstitial pneumonitis (inflammatory changes in the lungs)
• pulmonary fibrosis (disease of the lung tissue caused by increased formation of connective tissue between the
• 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)

Age in years
80 and over
Under 60

Total dose
100 x 103 IU
150-200 x 103 IU
200-300 x 103 IU
400 x 103 IU

Dose per week
15 x 103 IU
30 x 103 IU
30-60 x 103 IU
30-60 x 103 IU

Children and adolescents
There is insufficient experience with regard to the administration of bleomycin in paediatric patients. Until more
information is available, bleomycin should only be administered in children in exceptional circumstances and at special
facilities. If administration is indicated as part of a combination regimen the dosage is usually calculated based on the
body surface area and adjusted to meet the individual requirements of each patient. Current specialized protocols and
guidelines should be consulted for the appropriate treatment regimen.
Renal insufficiency
In case of renal failure, especially if creatinine clearance <35 ml / min, elimination of bleomycin is delayed. There are
no specific guidelines for dose adjustment in these patients, but it is recommended that patients with moderate renal
impairment (GFR 10-50 ml / min) should receive 75% of the usual dose administered at the usual dosing intervals and
patients severe renal failure (GFR below 10 ml / minute) should receive 50 % of the usual dose, given at the normal
dosing interval. No dose adjustment is required dosing in patients with a GFR greater than 50 ml / minute.
Combination therapy
The dose might require adjustment when bleomycin is used in combination therapy.
The bleomycin dosage should be reduced in conjunction with radiotherapy since the risk of mucosal damage is
increased. Dose adjustment may also be required when bleomycin is used in combination chemotherapy. Details
regarding treatment regimens applied for certain indications can be found in the current literature.
Method of administration and preparation of the solution for injection:
N.B.: The entire contents of a vial (15000 IU) should be dissolved in the appropriate quantity of solvent for preparation
of the solution. The quantity of units required for the treatment is then taken from this solution.
Bleomycin should not be mixed with solutions of essential amino acids, riboflavin, ascorbic acid, dexamethasone,
aminophylline, benzylpenicillin, carbenicillin, cefalotine, cefazoline, diazepam, furosemide, glutathione, hydrogen
peroxide, hydrocortisone Na succinate, methotrexate, mitomycin, nafcillin, penicillin G, substances containing
sulphydryl groups, terbutaline, or thiols. As bleomycin forms chelating agents with bi- and tervalent cations it should not
be mixed with solutions that contain such ions (in particular copper).
Intramuscular injection
Dissolve the contents of a vial in 1-5 mL physiological saline solution. Since repeated i.m. injections at the same site
can cause local discomfort, it is recommended to change the injection site regularly. In the event of excessive local
discomfort, a local anaesthetic can be added to the injection solution, e.g. 1.5-2 mL lidocaine HCl 1%.
Intravenous injection
Dissolve the contents of a vial in 5-10 mL physiological saline solution and inject slowly over a period of 5-10 minutes.
Fast bolus injections are to be avoided, because they lead to high intrapulmonary plasma concentrations, increasing
the risk of lung damage.

• 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)
• swellings (due to fluid retention in the tissues)
• inflammatory skin reaction
• fever, chills and malaise

Accord Healthcare Limited
Sage House, 319, Pinner Road, Harrow
Middlesex HA1 4HF
United Kingdom
Wessling Hungary Kft
Fòti ùt 56, Budapest 1047,
This leaflet was last revised in 06/2016

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 stomatitis (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 volume)
• 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),
Reporting of side effects
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 Yellow Card Scheme Website: By reporting side effects you can help provide more information on the safety of this

5. How to store Bleomycin
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 carton and the vial after EXP. The expiry date
refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
For single use only. Discard any residues.
The reconstituted/diluted product should be used immediately.
Do not use Bleomycin if you notice any visible signs of deterioration in the product or the vial, e.g. discolouration of the
powder or damage to the vial and the seal.
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 bleomycin contains
- The active substance is bleomycin (as bleomycin sulphate).
Each vial contains 15,000 International Units (I.U.) of bleomycin (as bleomycin sulphate).
- The other ingredients are sodium hydroxide (for pH adjustment) and hydrochloric acid (for pH adjustment).
What Bleomycin looks like and contents of the pack
White to light yellowish 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, 10 and 100 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare Limited
Sage House, 319, Pinner Road, Harrow
Middlesex HA1 4HF
United Kingdom

Intravenous infusion
Dissolve the contents of a vial in 200-1,000 mL physiological saline solution.
Intra-arterial injection
Dissolve the contents of a vial of bleomycin in at least 5 mL physiological saline solution and inject over a period of
5-10 minutes.
Intra-arterial infusion
Dissolve bleomycin in 200-1,000 mL physiological saline solution. The infusion can be administered over a few hours to
a number of days. Heparin can be added to prevent thrombosis at the injection site, especially if the infusion is
administered over a longer period.
Injection or infusion into an artery supplying the tumour tends to exhibit higher efficacy than other systemic routes of
administration. The toxic effects are the same as with intravenous injection or infusion.
Subcutaneous injection
Dissolve the contents of a vial in maximum 5 mL physiological saline solution. Absorption following subcutaneous
injection is delayed and may resemble a slow i.v. infusion. This form of administration is rarely used. Care must be
taken to avoid intradermal injection.
Intratumoural injection
Bleomycin is dissolved in physiological saline solution, producing a concentration of 1-3 x 103 IU/mL; this solution is
then injected into the tumour and the surrounding tissue.
Intrapleural instillation
Following drainage of the pleural cavity, bleomycin dissolved in 100 ml physiological saline solution and instilled via the
puncture cannula or drainage catheter. The cannula or catheter is then removed. In order to ensure uniform distribution
of the bleomycin in the serous cavity, position of patient should be changed every 5 minutes for a period of 20 minutes.
Approximately 45% of Bleomycin will be absorbed; this has to be considered for total dose (body surface area, kidney
function, lung function).
Perivascular administration of bleomycin does not usually require any specific measures. If in doubt (highly
concentrated solution, sclerotic tissue, etc.) perfusion can be performed with a physiological saline solution.
The reconstituted/diluted product should be used immediately.
Single use only, the reconstituted solution is a clear pale yellow solution. Any unused solution should be discarded.
Special precautions for disposal and other handling
The general guidelines for safe handling of cytotoxic medicinal products must be adhered to. Appropriate precautions
should be taken to avoid contact with the skin, mucous membranes and eyes. In the event of contamination, the parts
affected should be washed thoroughly with water.
Urine produced for up to 72 hours after administration of bleomycin should be handled wearing protective clothing.
Information on treating an overdose
There is no specific antidote. It is virtually impossible to eliminate bleomycin from the body by dialysis.
The acute reaction following an overdose consists of hypotension, fever, tachycardia, and generalised shock.

Treatment is exclusively symptomatic. In the event of respiratory complications, the patient should be treated with a
corticosteroid and a broad-spectrum antibiotic. Usually the lung reaction to an overdose (fibrosis) is not reversible,
unless diagnosed at an early stage.

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