Skip to Content

BLEO-KYOWA

Active substance: BLEOMYCIN SULPHATE

View full screen / Print PDF » Download PDF ⇩
Transcript
PACKAGE LEAFLET: INFORMATION FOR THE USER

®

1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Bleomycin Sulphate equivalent to 15,000 IU(15×103 IU)

3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
4.1 Therapeutic indications

a. Squamous cell carcinoma affecting the mouth, nasopharynx and paranasal sinuses,
larynx, oesophagus, external genitalia, cervix or skin. Well differentiated tumours
usually respond better than anaplastic ones.
b. Hodgkin's disease and other malignant lymphomas, including mycosis fungoides.
c. Testicular teratoma.
d. Malignant effusions of serous cavities.
e. Secondary indications in which bleomycin has been shown to be of some value (alone
or in combination with of other drugs) include metastatic malignant melanoma,
carcinoma of the thyroid, lung and bladder.

4.2 Posology and method of administration
Adults:

Routes of administration
Bleomycin is usually administered intramuscularly but may be given intravenously (bolus
or drip), intra-arterially, intrapleurally or intraperitoneally as a solution in physiological
saline. Local injection directly into the tumour may occasionally be indicated.
Recommended dose and dosage schedules
Squamous cell carcinoma and testicular teratoma:
Used alone the normal dosage is 15×103 IU (1 vial) three times a week or 30×103 IU (2
vials) twice a week, either intramuscularly or intravenously. Treatment may continue on
consecutive weeks, or more usually at intervals of 3-4 weeks, up to a total cumulative dose
of 500×103 IU although young men with testicular tumours have frequently tolerated twice
this amount. Continuous intravenous infusion at a rate of 15×103 IU (1 vial) per 24 hours
for up to 10 days, or 30×103 IU (2 vials) per 24 hours for up to 5 days may produce a
therapeutic effect more rapidly. The development of stomatitis is the most useful guide to
the determination of individual tolerance of maximum therapeutic response. The dose may
need to be adjusted when bleomycin is used in combination chemotherapy. Use in elderly
or children - see below.
Malignant lymphomas:
Used alone the recommended dosage regimen is 15×103 IU (1 vial) once or twice a week,
intramuscularly, to a total dose of 225×103 IU (15 vials). Dosage should be reduced in the
elderly. The dose may need to be adjusted when bleomycin is used in combination
chemotherapy. Use in elderly or children - see below.
Malignant effusions:
After drainage of the affected serous cavity, 60×103 IU (4 vials) bleomycin dissolved in
100 ml physiological saline is introduced via the drainage needle or cannula. After
instillation, the drainage needle or cannula may be withdrawn. Administration may be
repeated if necessary subject to a total cumulative does of 500×103 IU (about 33 vials).
Use in elderly or children-see below.
Combination therapy:
Bleomycin is commonly used in conjunction with radiotherapy, particularly in treatment of
cancer of the head and neck region. Such a combination may enhance mucosal reactions
if full doses of both forms of treatment are used and bleomycin dosage may require
reduction, e.g. to 5×103 IU at the time of each radiotherapy fraction five days a week.
Bleomycin is frequently used as one of the drugs in multiple chemotherapy regimens (e.g.
squamous cell carcinoma, testicular teratoma, lymphoma). The mucosal toxicity of
bleomycin should be borne in mind in the selection and dosage of drugs with similar toxic
potential used in such combinations.
Elderly Patients:
The total dose of bleomycin used in the treatment of squamous cell carcinoma, testicular
teratoma or malignant effusions should be reduced as indicated below
80 and over
70-79
60-69

Paediatric population

100×103
150 - 200×103
200 - 300×103

Pulmonary toxicity of bleomycin is both dose-related and age-related. It may also occur
when lower doses are administered, especially in elderly patients, patients with reduced
kidney function, pre-existing lung disease, previous or concurrent radiotherapy to the
chest and in patients who need administration of oxygen. It is significantly enhanced by
thoracic radiation and by hyperoxia used during surgical anaesthesia.
The earliest symptom associated with pulmonary toxicity of bleomycin is dyspnoea. Fine
rales are the earliest sign. If pulmonary changes are noted, treatment should be
discontinued until it can be determined if they are drug related. Patients should be
treated with broad spectrum antibiotics and corticosteroids.

Powder for solution for injection
White to light yellowish, freeze-dried substance

Total dose (IU)

Bleomycin sulphate

4.4 Special warnings and precautions for use

Bleo-Kyowa

Age in Years

BLEO-KYOWA® Powder for solution for injection 15,000 IU

Dose per week (IU)
15×103
30×103
30 - 60×103

Administration of bleomycin to paediatrics should take place only under exceptional
circumstances and in special centres. The dosage should be based on that recommended
for adults and adjusted to body surface area or body weight.
Reduced kidney function
With serum creatinine values of 2-4 mg%, it is recommended to half the above dosages.
With serum creatinine above 4 mg%, a further reduction in dose is indicated.
Preparation of solution
For intramuscular injections the required dose is dissolved in up to 5 ml of suitable
solvents such as physiological saline. If pain occurs at the site of injection a 1% solution
of lignocaine may be used as a solvent.
For intravenous injections the dose required is dissolved in 5 - 200ml of physiological
saline and injected slowly or added to the reservoir of a running intravenous infusion. For
intra-arterial administration a slow infusion in physiological saline is used. For
intra-cavitary injection 60×103 IU is dissolved in 100ml normal saline.
For local injections bleomycin is dissolved in physiological saline to make a 1-3×103 IU/ml
solution.

4.3 Contra-indications

Bleomycin is contra-indicated in patients with acute pulmonary infection or chest X-ray
findings suggesting diffuse fibrotic changes or greatly reduced lung function.
Patients with a past history of hypersensitivity or idiosyncratic reaction to an analogue of
bleomycin.

R Resgistered Trade Mark

Patients undergoing treatment with bleomycin should have chest X-rays weekly. These
should continue to be taken for up to 4 weeks after completion of the course and
patients should be kept under clinical review for approximately 2 months. If
breathlessness or lung infiltrates appear, not obviously attributable to tumour or to
co-existent lung disease, administration of the drug must be stopped immediately and
patients should be treated with a corticosteroid and a broad spectrum antibiotic. High
oxygen concentrations should be used with caution in these cases.
Lung function tests which use 100% oxygen should not be used in patients who have
been treated with bleomycin. Lung function tests using less than 21% oxygen are
recommended as an alternative.
When bleomycin has been administered pre-operatively, reduced oxygen concentrations
should be used during operation and post operatively.
Patients should be carefully monitored under the following conditions and bleomycin
dosage should be reduced or prolong the dose interval based on clinical observation of
the patient: These clinical conditions include the following:
·
Patients treated previously or concurrently with radiation to the chest may
develop more frequent or severe toxicity.
·
Use with caution in patients with significant renal impairment as clearance may
be reduced and toxicity increased (see Section 4.2).
·
Use with caution in patients with severe heart disease or hepatic dysfunction as
toxicity may be increased.
·
Use with caution in patients with varicella as fatal systematic dysfunctions may
occur.
Because bleomycin treatment may give rise to shock, if any abnormalities appear,
withdraw bleomycin immediately, and take appropriate measures. (Because shock is
likely to develop in patients with malignant lymphomas at the 1st – 2nd administration,
you may start this drug treatment with lower dose and after establishing that no acute
reactions to the drug occur, increase the dose to the usual level).
With long-term administration of bleomycin, peplomycin or other analogies of bleomycin,
toxicity is thought to be additive, thus administration must be performed with care.
Attention should be paid to the appearance or exacerbation of infection and any bleeding
tendency.
In adults or adolescents capable of reproduction, effects on the sexual glands should be
considered.
Intravenous administration
Vascular pain may occur, therefore, it is important to pay due attention to concentration
of the injection and administration rate. Give intravenously as slowly as possible.
Intramuscular administration
Avoid repeated injections at the same site and innervated sites, particularly if
administering to paediatrics. If insertion of the injection needle evokes intense pain or if
blood flows back into the syringe, withdraw the needle immediately and inject at a
different site.

4.5 Interactions with other medicinal products and other forms of
interaction

When bleomycin is used as one of the drugs in multiple chemotherapy regimes the toxicity
of bleomycin should be borne in mind in the selection and dosage of drugs with similar
toxic potential. The addition of other cytotoxic drugs can necessitate changes and dose
alterations. Increased pulmonary toxicity has been noted when bleomycin is given with
cisplatin.

Previous or concurrent radiotherapy to the chest and/or administration of anti-tumour
agents (e.g. cisplatin) are important factors in increasing the incidence and severity of lung
toxicity such as interstitial pneumonia or pulmonary fibrosis.
Previous or concurrent radiotherapy to the head or neck is a factor increasing stomatitis
and angular stomatitis may deteriorate. It may cause inflammation of pharyngolaryngeal
mucosa infrequently resulting in hoarseness.
Because of bleomycin's sensitisation of lung tissue, patients who have received bleomycin
pre-operatively are at greater risk of developing pulmonary toxicity when oxygen is
administered at surgery and a reduction in inspired oxygen concentration during operation
and post-operatively is recommended. (See Section 4.4)
In patients treated for testicular cancer with a combination of bleomycin and vinca
alkaloids a syndrome has been reported corresponding to Raynaud’s disease, ischaemia
which can lead to necrosis of peripheral parts of the body (fingers, toes, nose tip).
The following clinical incompatibilities have been noted:-Cytotoxics possibly reduce the
absorption of phenytoin. Concomitant use of bleomycin with clozapine should be avoided
due to an increased risk of agranulocytosis.

4.6 Fertility, pregnancy and lactation

Pregnancy
The administration of this drug to pregnant patients, or women suspected of being
pregnant, is not recommended. The use of bleomycin should be avoided whenever
possible during pregnancy, particularly during the first trimester.
Breastfeeding
Bleomycin should not be given to mothers who are breast feeding.
Fertility
Bleomycin can cause congenital malformations. Conception during and six months after
treatment is not advisable. Women should not become pregnant during and six months
after treatment.

4.7 Effects on ability to drive and use machines

This depends on the patient’s condition and should be considered in co-operation with the
doctor.

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 pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It
may harm them, even if their symptoms are the same as yours.
If you get any side effects, talk to your doctor or nurse. This includes any
possible side affects not listed in this leaflet. See section 4.

-

What is in this leaflet

Other medicines and Bleo-Kyowa
Tell your doctor or pharmacist if you are using, have recently used or might use any
other medicines, as some medicines could interact with Bleo-Kyowa.
When Bleo-Kyowa is used with vinca alkaloids (another type of cancer drug) to
treat cancer of the testes, Raynauds’s disease (poor blood circulation which makes
the toes and fingers numb and pale) has been reported.
Use of Bleo-Kyowa together with cisplatin or ratiation to the chest can cause
interstitial pneumonia (serious inflamation of the lungs) and pulmonary fibrosis
(scarring of the lungs which leads to shortness of breath).
Use of Bleo-Kyowa with clozapine should be avoided, as it may cause more severe
reduction in number of white blood cells which makes infections more likely
(agranuclocytosis).

1.
2.
3.
4.
5.
6.

What Bleo-Kyowa is and what it is used for
What you need to know before you use Bleo-Kyowa
How to use Bleo-Kyowa
Possible side effects
How to store Bleo-Kyowa
Contents of the pack and other information

Use of cytotoxics (medicines that kill cancer cells) may lower the absourption of
phenytoin.

1.

WHAT BLEO-KYOWA IS AND WHAT IT IS USED FOR

If you are planning to have a baby, ask your doctor for advice before using
Bleo-Kyowa.

Bleo-Kyowa is an anti-cancer drug (chemotherapy) used for treating certain types of
cancer. Bleo-Kyowa is used to treat cancer known as squamous cell carcinoma
which can affect the mouth, nose, throat, skin, cervix or external genitalia.
It is also used to treat Hodgkin's disease and other types of cancer of the blood, as
well as to treat fluid producing cancers in the cavity around the lungs or in the
abdomen, and to treat testicular teratoma.
Bleo-Kyowa is also of value in treating malignant melanoma (a type of skin cancer)
and thyroid, lung and bladder cancer.

2.

WHAT YOU NEED TO KNOW BEFORE YOU USE BLEO-KYOWA

Do not use Bleo-Kyowa:
• if you are allergic (hypersensitive) to bleomycin or to any similar anti-cancer
medicine
• if you have a chest infection
• if you have scarring of the lungs
• if you have greatly reduced lung function
If any of these apply to you, tell your doctor.
Warnings and precautions
Talk to your doctor before using Bleo-Kyowa if you have or have recently had any of
the following:







kidney problems
lung problems or you have been receiving oxygen
severe heart disease
liver function that is impaired
chicken pox
radiation to the chest

You must also tell your doctor if you have an operation planned as it may be
neccessary to adjust your treament with Bleo-Kyowa.

Pregnancy, breast-feeding and fertility
If you are pregnant, breast-feeding, or think you may be pregnant do not take this
medicine.

Driving and using machines
A few people have reported that they feel tired or weak after the treatment. Do not
drive or use any tools or machines if you are affected.

3.

HOW TO USE BLEO-KYOWA

Bleo-Kyowa powder from one or more vials will be dissolved in saline (a weak salt
solution that mixes well with body fluids). The solution is usually given by injection
in to muscle tissue or a blood vessel or into the chest or abdominal cavity
depending on the type of cancer. Occasionally, it is injected directly into a tumour.
The usual treatment is for 2 or 3 days in one week and may be repeated in
subsequent weeks. Sometimes the treatment is given on consecutive days for up to
5 or 10 days.
The precise dosage, frequency of dosing and duration of treatment with
Bleo-Kyowa will depend on your age, weight, medical condition and whether
Bleo-Kyowa is being given in combination with other drug treatment.
If other medicines or radiotherapy are also being used in your treatment or if you
have kidney disease or reduced kidney function, the amount of Bleo-Kyowa given
to you may be reduced.
Use in children and adolescents
The dose is calculated in relation to child body weight and such treatment will
probably take place under the supervision of a specialist treatment centre.
If during treatment you develop a dry cough, breathlessness, rapid breathing or
anything else which suggests your lungs might be affected, you may require to be
monitored by X-rays of your chest that could continue up to 4 weeks after the end of
treatment.
LFT-BLO-GB-001

If you are given more Bleo-Kyowa than you should
If you have been accidentally given a higher dose you may experience symptoms
such as fever, low blood pressure and rapid pulse. Your doctor may give you
supportive treatment for any symptoms that may occur.

4.

POSSIBLE SIDE EFFECTS

Like all medicines, Bleo-Kyowa can cause side effects, although not everybody
gets them. These might occur at the time of treatment or might occur at some later
time.
If you notice any of the following reactions tell your doctor immediately:
• breathlessness
• inflamation of the lungs (interstitial pneumonia) – fever, chills, shortness of
breath or a cough
• severe allergic reaction – you may experience a sudden itchy rash (hives),
swelling of the hands, feet, ankles, face, lips, mouth or throat (which may
cause difficulty in swallowing or breathing), and you may feel you are going to
faint.
These are serious side effects. You may need urgent medical attention.
If you experience any of the following tell your doctor or nurse as soon as
possible:
Very common: (these may affect more than 1 in 10 patients)
fever on the day of treatment
loss of appetite and weight loss
nausea and vomiting
lung problems
sore mouth and mouth ulcers
changes in skin colour, or itchy skin
hardening, thickening, redness, tenderness or swelling of the tips of the
fingers
• hair loss
• ridging of nails, blisters on pressure points e.g. elbows
• numbness, pain or colour changes to the fingers, toes and tip of the nose,
and hardening and tightening of skin








Common: (these may affect between 1 in 10 and 1 in 100 patients)





headache
bleeding
skin rash, redness of the skin
soreness at the corners of the mouth

Uncommon: (these may affect between 1 in 100 and 1 in 1,000 patients)








dizziness
changes in urinating or pain when urinating
low white blood cell count
liver problems
blood vessel changes (narrowed or enlarged)
diarrhoea
pain, swelling, redness or tenderness at the site of the injection or at the site
of the tumour

The following side effects have been reported since the marketing of Bleo-Kyowa
but the frequency for them to occur is not known:
Overwhelming infection (sepsis), severe reduction in blood cells (pancytopenia),
reduction in blood platelets (thrombocytopenia), reduction in red blood cells
(anaemia), neutropenia (reduced white blood cells), chest pain, heart attack,
reduced blood flow to the fingers, toes and tip of the nose (Raynaud’s syndrome or
digital ischaemia), blood clots (embolism), blood clotting (thrombosis) and a type of
stroke (cerebral infarction).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any
possible side effects not listed in this leaflet. You can also report side effects
directly via the Yellow Card Scheme, 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 BLEO-KYOWA

Keep out of the reach and sight of children.

4.8 Undesirable effects

The most frequently observed adverse reactions in 1613 patients
receiving bleomycin were pulmonary manifestations such as
interstitial pneumonia or pulmonary fibrosis (10.2%), sclerosis of
skin, pigmentation (40.6%), fever and rigors (39.8%), alopecia
(29.5%), anorexia and weight decrease (28.7%), general malaise
(16.0%), nausea and vomiting (14.6%), stomatitis (13.3%) and nail
changes (11.2%).
Common
System Organ Class Very Common
Uncommon
>1/100 to < 1/10 >1/1,000 to <1/100
>1/10
Neoplasms, Benign,
Malignant and
Unspecified (including
Cysts and Polyps)

Pain at the site of
tumour

Blood and lymphatic
system disorders

Leukopenia

Metabolism and
Nutrition disorders

Anorexia

Vascular disorders

Haemorrhage

Respiratory, thoracic
and mediastinal
disorders

Interstitial
pneumonia;
pulmonary
fibrosis
Weight
decrease;
nausea;
vomiting;
stomatitis

Nervous system
disorders

Gastrointestinal
disorders

Hepatobilliary
disorders
Skin and
subcutaneous tissue

Bleo-Kyowa should be kept in its original packaging and stored at 2-8C.
This medicine will normally be stored by the doctor providing your treatment or by
another qualified person such as a nurse or pharmacist.
Avoid contact of Bleo-Kyowa on the skin. Each vial of Bleo-Kyowa is labelled with a
'use-by' date and the medicine should not be used after this date.
After being treated with Bleo-Kyowa, any remaining bleomycin solution or
equipment used for the treatment will be safely disposed of by your nurse or doctor.
Medicines should not be disposed of via wastewater or household waste. These
measures will help to protect the environment.

6.

FURTHER INFORMATION

What Bleo-Kyowa contains
-

The active substance is bleomycin sulphate
There are no other ingredients

What Bleo-Kyowa looks like and contents of the pack
Bleo-Kyowa is a white to yellow-ish powder which is mixed with saline before
injection. It is packaged in glass vials with a rubber stopper and aluminium seal.
Marketing Authorisation Holder
ProStrakan Limited
Galabank Business Park
Galashiels
TD1 1QH
UK

Manufacturer
Aesica Queenborough Limited
North Road
Queenborough
Kent
ME11 5EL

Tel: 01896 664000
This medicinal product is authorised in the Member States of the EEA under
the following names:

Musculoskeletal
and connective
tissue disorders
Renal and Urinary
disorders

Headache

Alopecia; skin
hypertrophy;
pigmentation;
deformation
and
discolouration
of the nail;
scratch
dermatitis
Scleroderma

General disorders and Fever; rigors;
administration site
malaise
conditions

Dizziness
Shock; vein wall
hypertrophy;
venous stenosis

Angular
stomatitis

Rash; urticaria;
erythroderma

Diarrhoea

Hepatocellular
injury

Oliguria; dysuria;
pollakiuria; urinary
retention; polyuria;
feeling of residual
urine
Injection site
induration

Like most cytotoxic agents bleomycin can give rise both to
immediate and to delayed toxic effects. The most immediate effect is
fever on the day of injection. Anorexia, tiredness or nausea also may
occur. Pain at the injection site or in the region of the tumour has
occasionally been reported, and other rare adverse effects are
hypotension and local thrombophlebitis after intravenous
administration. Fever may develop with a lag time of 4-5 hours or
more after the administration of this drug. Because a doseresponse relation exists between the fever and dose at a given time,
if the fever is severe, appropriate measures should be taken such as
administering a reduced dose at shorter intervals, or antihistaminic
and antipyretic agents before and/or after administration of this drug.
The majority of patients who receive a full course of bleomycin
develop lesions of the skin or oral mucosa. Induration,
hyperkeratosis, reddening, tenderness and swelling of the tips of the
fingers, ridging of the nails, bulla formation over pressure points
such as elbows, loss of hair and stomatitis are rarely serious and
usually disappear soon after completion of the course.
The most serious delayed effect is interstitial pneumonia, which may
develop during, or occasionally after, a course of treatment. This
condition may sometimes develop into fatal pulmonary fibrosis,
although such an occurrence is rare at recommended doses.
Previous or concurrent radiotherapy to the chest is an important
factor in increasing the incidence and severity of lung toxicity.
A few cases of acute fulminant reactions with hyperpyrexia and
cardiorespiratory collapse have been observed after intravenous
injections of doses higher than those recommended. Hypotension,
hyperpyrexia and drug-related deaths have been reported rarely
following intra-cavitary instillation of bleomycin.
During post-marketing surveillance the following events have been
reported: sepsis, pancytopenia, thrombocytopenia, anaemia,
neutropenia, chest pain, myocardial infarction, Raynaud’s syndrome,
embolism, thrombosis, digital ischaemia and cerebral infarction.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the
medicinal product is important. It allows continued monitoring of the
benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties

ATC code: LO1D C01, other cytotoxic antibiotics
Bleomycin is a basic, water-soluble glycopeptide with cytotoxic
activity. The mechanism of action of bleomycin is believed to involve
single-strand scission of DNA, leading to inhibition of cell division, of
growth and of DNA synthesis in tumour cells.
Apart from its antibacterial and antitumour properties, bleomycin is
relatively free from biological activity. When injected intravenously it
may have a histamine-like effect on blood pressure and may cause
a rise in body temperature.

5.2 Pharmacokinetic properties

Bleomycin is administered parenterally. After intravenous (IV)
administration of a bolus dose of 15×103 IU/m2 body surface, peak
concentrations of 1 to 10 IU are achieved in plasma. Following the
intramuscular (IM) injection of 15×103 IU peak plasma concentrations
of about 1 IU/ml have been reported. The peak plasma concentration
is reached 30 minutes after an IM injection. Continuous infusion of
bleomycin 30×103 IU daily, for 4 to 5 days, resulted in an average
steady state plasma concentration of 100-300 milli IU/ml. After IV
injections of bleomycin in a dose of 15×103 IU/m2 body surface, the
area under the serum concentration curve is, on average, 300 milli
IU x min x ml-1.
Bleomycin is only bound to plasma proteins to a slight extent.
Bleomycin is rapidly distributed in body tissues, with the highest
concentrations in skin, lungs, peritoneum and lymph. Low
concentrations are seen in the bone marrow. Bleomycin could not be
detected in cerebrospinal fluid after intravenous injection. Bleomycin
appears to cross the placental barrier.
The mechanism for biotransformation is not yet fully known.
Inactivation takes place during enzymatic breakdown by bleomycin
hydrolase, primarily in plasma, liver and other organs and, to a much
lesser degree, in skin and lungs. When bleomycin was administered
as an IV bolus injection in a dose of 15×103 IU/m2 body surface,
initial and terminal half-lives were 0.5 and 4 hours respectively.
Given as a continuous intravenous infusion in a dose of 30×103 IU
daily for 4 to 5 days bleomycin disappears from plasma with initial
and terminal half-lives of about 1.3 hours and 9 hours, respectively.
About two thirds of the administered drug is excreted unchanged in
the urine, probably by glomerular filtration. Approximately 50% is
recovered in the urine in the 24 hours following an IV or IM injection.
The rate of excretion, therefore, is highly influenced by renal
function; concentrations in plasma are greatly elevated if usual
doses are given to patients with renal impairment with only up to
20% excreted in 24 hours. Observations indicate that it is difficult to
eliminate bleomycin from the body by dialysis.

5.3 Pre-clinical safety data

Animal experiences have revealed that bleomycin, like most
cytotoxics, may have teratogenic and carcinogenic potential.

Bleomycin has been reported to cause fibrosarcoma and renal
carcinoma in a laboratory animal (rat) administered subcutaneously.
Bleomycin has been reported to cause foetal malformation in
laboratory animals (mice and rats).

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
None

6.2 Incompatibilities

Bleomycin solution should not be mixed with solutions of essential
amino acids, riboflavine, ascorbic acid, dexamethasone,
aminophylline or frusemide.

6.3 Shelf life
3 years.

6.4 Special precautions for storage
Protect from light. Store at 2℃-8℃.

6.5 Nature and contents of container

5ml colourless glass vials with rubber closure and aluminium cap
containing freeze dried bleomycin sulphate equivalent to 15,000 IU
Ten vials per carton.

6.6 Special precautions for disposal and other handling
Bleomycin should be handled with care. Precautions should be
taken to avoid bleomycin coming into contact with skin, mucous
membranes or eyes, but in the event of contamination the affected
parts should be washed with water.

7. MARKETING AUTHORISATION HOLDER
ProStrakan Limited
Galabank Business Park
Galashiels
TD1 1QH
UK

8. MARKETING AUTHORISATION NUMBER
PL16508/0046

9. DATE OF FIRST AUTHORISATION/RENEWAL OF
AUTHORISATION
03/07/2006

10. DATE OF REVISION OF THE TEXT
06/11/2014

4.9 Overdose

The acute reaction to an overdosage of bleomycin would probably
include hypotension, fever, rapid pulse and general symptoms of
shock. Treatment is purely symptomatic. In the event of respiratory
complications the patient should be treated with a corticosteroid and
a broad-spectrum antibiotic. There is no specific antidote to
bleomycin.

Bleo-Kyowa.
This leaflet was last revised in 11/2014.
LFT-BLO-GB-001
F-2-2AH

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

(web1)