Bleomycin

Bleomycin

Usual Diluents

Dilution Data

ADMINISTRATION / DILUTION

Bleomycin for injection may be given by the intramuscular, intravenous, or subcutaneous or intrapleural routes.    
Intramuscular or Subcutaneous:The bleomycin for injection, USP 15 units vial should be reconstituted and dissolved with 1 to 5 mL of sterile water for injection, USP, sodium chloride injection, 0.9%, USP, or bacteriostatic water for injection, USP. The bleomycin for injection, USP 30 units vial should be reconstituted and dissolved with 2 to 10 mL of the above diluents.
Intravenous: The contents of the 15 units or 30 units vial should be dissolved in 5 mL or more or 10 mL or more, respectively of sodium chloride injection, 0.9%, USP, and administered slowly over a period of 10 minutes
.
Stability:  The sterile powder is stable under refrigeration 2°-8°C (36°-46°F) and should not be used after the expiration date is reached.   Bleomycin for injection, USP is stable for 24 hours at room temperature in 0.9 % sodium chloride injection. 

INDICATIONS AND USAGE
Bleomycin for injection should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents.

Squamous Cell Carcinoma
Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to bleomycin is poorer in patients with previously irradiated head and neck cancer.

Lymphomas
Hodgkin's Disease, non-Hodgkin's lymphoma.

Testicular Carcinoma
Embryonal cell, choriocarcinoma, and teratocarcinoma.

Bleomycin has also been shown to be useful in the management of:
Malignant Pleural Effusion
Bleomycin is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions.

CONTRAINDICATIONS
Bleomycin is contraindicated in patients who have demonstrated a hypersensitive or an idiosyncratic reaction to it.

DOSAGE AND ADMINISTRATION
BECAUSE OF THE POSSIBILITY OF AN ANAPHYLACTOID REACTION, LYMPHOMA PATIENTS SHOULD BE TREATED WITH 2 UNITS OR LESS FOR THE FIRST TWO DOSES. IF NO ACUTE REACTION OCCURS, THEN THE REGULAR DOSAGE SCHEDULE MAY BE FOLLOWED.

The following dose schedule is recommended: Squamous cell carcinoma, non-Hodgkin's lymphoma, testicular carcinoma - 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.

Hodgkin's Disease - 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. After a 50% response, a maintenance dose of 1 unit daily or 5 units weekly intravenously or intramuscularly should be given.

Pulmonary toxicity of bleomycin appears to be dose related with a striking increase when the total dose is over 400 units. Total doses over 400 units should be given with great caution.

Note: When bleomycin for injection is used in combination with other antineoplastic agents, pulmonary toxicities may occur at lower doses.

Improvement of Hodgkin's Disease and testicular tumors is prompt and noted within 2 weeks. If no improvement is seen by this time, improvement is unlikely. Squamous cell cancers respond more slowly, sometimes requiring as long as 3 weeks before any improvement is noted.

Malignant Pleural Effusion - 60 units administered as a single dose bolus intrapleural injection.

Administration ------------------------------------
Bleomycin for injection may be given by the intramuscular, intravenous, or subcutaneous or intrapleural routes.

Intramuscular or Subcutaneous
The bleomycin for injection, USP 15 units vial should be reconstituted and dissolved with 1 to 5 mL of sterile water for injection, USP, sodium chloride injection, 0.9%, USP, or bacteriostatic water for injection, USP. The bleomycin for injection, USP 30 units vial should be reconstituted and dissolved with 2 to 10 mL of the above diluents.

Intravenous
The contents of the 15 units or 30 units vial should be dissolved in 5 mL or more or 10 mL or more, respectively of sodium chloride injection, 0.9%, USP, and administered slowly over a period of 10 minutes

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Intrapleural
60 units of bleomycin is dissolved in 50-100 mL sodium chloride injection 0.9% and administered through a thoracostomy tube following drainage of excess pleural fluid and confirmation of complete lung expansion. The literature suggests that successful pleurodesis is, in part, dependent upon complete drainage of the pleural fluid and reestablishment of negative intrapleural pressure prior to instillation of a sclerosing agent. Therefore, the amount of drainage from the chest tube should be as minimal as possible prior to instillation of bleomycin. Although there is no conclusive evidence to support this contention, it is generally accepted that chest tube drainage should be less than 100 mL in a 24 hour period prior to sclerosis. However, bleomycin instillation may be appropriate when drainage is between 100-300 mL under clinical conditions that necessitate sclerosis therapy. The thoracostomy tube is clamped after bleomycin instillation. The patient is moved from the supine to the left and right lateral positions several times during the next four hours. The clamp is then removed and suction reestablished. The amount of time the chest tube remains in place following sclerosis is dictated by the clinical situation.

The intrapleural injection of topical anesthetics or systemic narcotic analgesia is generally not required.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Stability
The sterile powder is stable under refrigeration 2°-8°C (36°-46°F) and should not be used after the expiration date is reached.

Bleomycin for injection, USP should not be reconstituted or diluted with 5% dextrose injection or other dextrose containing diluents. When reconstituted in 5% dextrose injection and analyzed by HPLC, bleomycin for injection, USP demonstrates a loss of A2 and B2 potency that does not occur when bleomycin for injection, USP is reconstituted in 0.9% sodium chloride injection, USP.

Bleomycin for injection, USP is stable for 24 hours at room temperature in 0.9 % sodium chloride injection.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED
Bleomycin for Injection, USP contains sterile bleomycin sulfate equivalent to 15 units or 30 units of bleomycin. Bleomycin for Injection, USP is supplied as follows:

NDC Number
0703 3154-01 15 Units per Vial Individually packaged
0703 3155-01 30 Units per Vial Individually packaged

Store dry powder under refrigeration 2°-8°C (36°-46°F).

Handling and disposal: Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents, US Government Printing Office, Washington, DC 20402. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA 1985; 253(11):1590 1592. National Study Commission on Cytotoxic Exposure-Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115. Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia 1983; 1:426-428. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians 1983; (Sept/Oct) 258-263. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm 1990; 47:1033-1049. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines), Am J Health-Syst Pharm, 1996; 53:1669-1685