Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Accord Healthcare Limited, Sage House, 319, Pinner Road, North Harrow, Middlesex HA1 4HF, United Kingdom
Bleomycin can be used in the treatment of:
Bleomycin can be used as a monotherapy, but is usually combined with other cytostatics and/or radiation therapy.
Warning: Posology for all therapeutic indications is provided in IU and not in mg. Some hospital protocols may state use “mg” instead of Units (U or IU). This mg value refers to mg-activity and not to mg-dry material as these reflect different values.
Our recommendation is to ignore this posology in mg and actually use the posology in International Units (IU) as described in this SmPC for the relevant therapeutic indications.
Please note that 1 mg dry substance is equivalent to at least 1500 IU. Yet we strongly recommend not to use this conversion as this may result in overdosage because of the differences between mg-activity and mg-dry material. This product should therefore only be prescribed in international units (IU).
Bleomycin should only be used under the strictest supervision of a physician specialised in the use of oncolytic medicinal products, preferably in a hospital with experience in such therapies
Bleomycin may be administered intravenously, intramuscularly, intra-arterially, subcutaneously or by intrapleural instillation. Local injection directly into the tumour may occasionally be indicated.
1) Squamous cell carcinoma
Intramuscular or intravenous injection of 10-15 × 103 IU/m² body surface area (BSA), once or twice a week, at intervals of 3-4 weeks up to a lifetime cumulative dose of 360 × 103 IU.
Intravenous infusion of 10-15 × 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 x103 IU/m² BSA, once or twice a week, up to a cumulative total dose of 225 x103 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 x103 IU/m² BSA once or twice a week, at intervals of 3-4 weeks up to a total cumulative dose of 400 × 103 IU.
The intravenous infusion of the dose of 10-15 × 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 × 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 lifetime 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 x103 IU (corresponding to 225 × 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 x103 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 observed.
The total dose of bleomycin in elderly patients should be reduced according to the following table:
| Age in years | Total dose | Dose per week |
|---|---|---|
| 80 and over | 100 × 103 IU | 15 × 103 IU |
| 70-79 | 150-200 × 103 IU | 30 × 103 IU |
| 60-69 | 200-300 × 103 IU | 30-60 × 103 IU |
| Under 60 | 400 × 103 IU | 30-60 × 103 IU |
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.
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 in patients with a GFR greater than 50 ml/minute.
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.
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.
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%.
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.
Dissolve the contents of a vial in 200-1,000 mL physiological saline solution.
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.
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.
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.
Bleomycin is dissolved in physiological saline solution, producing a concentration of 1-3 x103 IU/mL; this solution is then injected into the tumour and the surrounding tissue.
Following drainage of the pleural cavity, bleomycin, dissolved in 100 ml physiological saline solution, is 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, the position of the 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 the 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.
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.
2 years.
The reconstituted/diluted product should be used immediately.
Store in a refrigerator (2°C-8°C).
For storage conditions after reconstitution/dilution of the medicinal product, see section 6.3.
6 ml Type I tubular clear glass vial, closed with bromobutyl rubber stopper and sealed with a flip-off aluminium seal.
Availbale in pack of 1vial. 10 and 100 vials.
Not all pack sizes may be marketed.
Single use only, the reconstituted solution is a clear pale yellow solution. Any unused solution should be discarded.
Safe 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.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.
Instructions for preparation of the solution for injection/infusion:
The entire contents of a vial (15 × 103 IU) should be dissolved in the appropriate quantity of solvent for preparation of the solution. The quantity of IU required for the treatment is then taken from this solution.
Dissolve the contents of a vial in 1-5 mL physiological saline solution. 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%.
Dissolve the contents of a vial in 5-10 mL physiological saline solution.
Dissolve the contents of a vial in 200-1,000 mL physiological saline solution.
Dissolve the contents of a vial of bleomycin in at least 5 mL physiological saline solution.
Dissolve bleomycin in 200-1,000 mL physiological saline solution. Heparin can be added to prevent thrombosis at the injection site, especially if the infusion is administered over a longer period.
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.
Following drainage of the pleural cavity, bleomycin dissolved in 100 mL physiological saline solution, is 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, the patient’s position should be changed over 20 minutes at an interval of 5 minutes.
Bleomycin is dissolved in physiological saline solution, producing a concentration of 1-3 X 103 IU/mL.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
