Posology : מינונים

4.2 Posology and method of administration

Bleomycin is administered parenterally by intramuscular injection, intravenous injection/infusion, intraarterial injection/infusion, subcutaneous injection, intratumoral injection or intracavitary instillation.
Posology
Adults
1)   Squamous cell carcinoma
Intramuscular or intravenous injection of 10-15 units (USP)/m². Intravenous infusion of 10-15 units (USP)/m²/day over 6-24 hours for 4 to 7 consecutive days at intervals of 3-4 weeks.
2)   Hodgkin's lymphoma and non-Hodgkin's lymphoma
Intramuscular or intravenous injection of 5-10 units (USP)/m² once or twice a week. Due to the possibility of anaphylactoid reactions, in lymphoma patients the first two doses should not exceed 1–2 units. If no acute reactions occur, the regular dosage regimen can be administered.
3)   Testicular carcinoma
Intramuscular or intravenous injection of 10-15 units (USP)/m² BSA once or twice per week.
The dose of 15–20 units (USP)/m2 BSA/day is administered by intravenous infusion over 6–24 hours on 5–6 consecutive days at intervals of 3–4 weeks.
4)   Malignant effusions
60 units (USP) in 100 ml physiological saline intrapleurally or intraperitoneally as a single dose and repeated, if necessary.
5)   Refractory warts
Intralesionally injection of bleomycin has been given as a 0.1 % solution, usually as a 0.1 ml injection.
In cases of Hodgkin's disease and testicular cancer, improvement occurs rapidly and may be observed within two weeks. If no improvement is noted by this point, subsequent improvement is unlikely. Squamous cell carcinomas respond more slowly; in some cases, it can take three weeks before any improvement is observed.
Total doses of bleomycin in patients not older than 60 years should not exceed 400 units (USP) (approximately 225 units/m² body surface), unless an examination of the lung function has ensured continued administration. Doses may need to be adjusted when given in combination with other antineoplastic agents or with radiotherapy, and in patients older than 60 years (see below).

Elderly patients

The total dose should be reduced as indicated below
Age in years                 Total dose                           Dose per week 80 and over                  100 units (USP)                       15 units (USP) 70-79                        150-200 units (USP)                   30 units (USP) 60-69                        200-300 units (USP)                 30-60 units (USP) Under 60                     400 units (USP)                     30-60 units (USP) 

Children
If administration of bleomycin to children is indicated, the dosage should be based on that recommended for adults and adjusted to body surface area.
Reduced renal function
In patients with reduced kidney function, doses should be reduced. If creatinine clearance decreases to 20 ml/min, 50% of bleomycin dose should be given.


Combination therapy
When used in combination with radiotherapy, the dose of bleomycin should be reduced. Dose adjustments may also be necessary in the context of combination chemotherapy.


Method of administration/preparation of solutions
Note: For preparation of the solution dissolve the whole content of a vial (15 units) in the appropriate amount of solvent. From this solution use an aliquot according to the units needed 2        2 for treatment. Example: required dosage 8.5 units (5 units /m x 1.7 m ); dissolve the content of a vial (15 units) in 5 ml solvent; take out 2.83 ml (8.5 units) for application.
Intramuscular injection
Dissolve the contents of one vial in 1-5 mL physiological saline. Since repeated IM injections into the same site can lead to local reactions, it is advisable to change the injection site regularly. In case of excessive local reactions, a local anesthetic, e.g. 1.5 -2 mL lidocaine HCl 1% may be added to the solution for injection.
Intravenous injection
Dissolve the contents of a vial in 5-10 ml of physiological saline solvent and administer over a period of 5-10 minutes. Avoid a fast bolus injection, which will give a high blood concentration passing through the lungs, increasing the risk of damage to the lungs.
Intravenous infusion
Dissolve the contents of one vial in 200-1000 mL of physiological saline.
Intra-arterial injection
Dissolve the contents of one vial of bleomycin in at least 5 mL physiological saline and inject over a period of 5-10 minutes.
Intra-arterial infusion
Dissolve bleomycin in 200-1000 mL physiological saline. The infusion can be administered over a few hours to several days. Heparin may be added to prevent thrombosis at the injection site, especially if the infusion is administered over a long period of time.
Injection or infusion into an artery supplying the tumor tends to be more effective than other systemic routes of administration. The toxic effects are the same as those associated with intravenous injection or infusion.
Subcutaneous injection
Absorption after subcutaneous injection is delayed and may be similar to that associated with slow IV infusion. This method of administration is rarely used. Intradermal injection must be carefully avoided.
Intratumoral injection
Bleomycin is dissolved in physiological saline to make a 1-3 units (USP)/ml solution which is injected into the tumor and its surrounding tissues. This form of application is rarely used.
Intracavitary instillation
Following aspiration of the pleural or peritoneal cavity, bleomycin dissolved in physiological saline is instilled via the needle or catheter used for aspiration. The needle or catheter is then removed. In order to ensure the uniform dispersion of bleomycin within the serous cavity the patient's posture should be changed every 5 minutes, for 20 minutes.
Extravasal administration of bleomycin does not usually demand extraordinary precautions. In case of doubt (concentrated solution, sclerotic tissue, etc.) perfusion with physiological saline may be performed.