Bleomycin

Bleomycin for Injection, USP 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 for Injection, USP 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.

Although the exact mechanism of action of bleomycin is unknown, available evidence indicates that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis. Bleomycin is known to cause single, and to a lesser extent, double-stranded breaks in DNA. In in vitro and in vivo experiments, bleomycin has been shown to cause cell cycle arrest in G2 and in mitosis. When administered into the pleural cavity in the treatment of malignant pleural effusion, bleomycin acts as a sclerosing agent.

Because of the possibility of an anaphylactoid reaction, lymphoma patients should be treated with 2 units or less for the first 2 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/m 2 ) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly. Hodgkin's Disease – 0.25 to 0.50 units/kg (10 to 20 units/m 2 ) 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 for injection appears to be dose-related with a striking increase when the total dose is over 400 units.

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

WARNING It is recommended that Bleomycin for Injection, USP be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Pulmonary fibrosis is the most severe toxicity associated with bleomycin. Patients receiving bleomycin must be observed carefully and frequently during and after therapy. It should be used with extreme caution in patients with significant impairment of renal function or compromised pulmonary function. Pulmonary toxicities occur in 10% of treated patients. In approximately 1%, the nonspecific pneumonitis induced by bleomycin progresses to pulmonary fibrosis and death. Although this is age and dose related, the toxicity is unpredictable.

Pulmonary The most serious side effects are pulmonary adverse reactions, occurring in approximately 10% of treated patients. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Approximately 1% of patients treated have died of pulmonary fibrosis. Pulmonary toxicity is both dose and age related, being more common in patients over 70 years of age and in those receiving over 400 units total dose. This toxicity, however, is unpredictable and has been seen in young patients receiving low doses. Some published reports have suggested that the risk of pulmonary toxicity may be increased when bleomycin is used in combination with G-CSF (filgrastim) or other cytokines. However, randomized clinical studies completed to date have not demonstrated an increased risk of pulmonary complications in patients treated with bleomycin and G-CSF.

Drugs that Can Affect Renal Clearance Because bleomycin is eliminated predominantly through renal excretion, the administration of nephrotoxic drugs with bleomycin may affect its renal clearance. Specifically, in one report of 2 children receiving concomitant cisplatin with bleomycin, total body clearance of bleomycin decreased from 39 to 18 mL/min/m 2 as the cumulative dose of cisplatin exceeded 300 mg/m 2. Terminal half-life of bleomycin also increased from 4.4 to 6 hours. Fatal bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.

Store refrigerated between 2° and 8°C (36° and 46°F). The sterile powder is stable under refrigeration and should not be used after the expiration date is reached. Bleomycin for Injection, USP is stable for 24 hours at room temperature in Sodium Chloride.