Bloicin-S

Each vial contains Bleomycin (as sulfate), USP 15 units.

Pharmacology: Pharmacodynamics: 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.
Pharmacokinetics: Bleomycin is administered parenterally. After intravenous (IV) administration of a bolus dose of 15 x 10³ IU/m² body surface, peak concentrations of 1 to 10 IU are achieved in plasma. Following the intramuscular (IM) injection of 15 x 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 x 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 x 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 bio-transformation 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 x 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 x 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.

Squamous cell carcinoma: Head and neck, penis, cervix, and vulva.
Lymphomas: Hodgkin's or non-Hodgkin's disease Testicular carcinoma.
For the treatment of malignant pleural effusion and prevention of recurrent pleural effusion.

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 SULFATE appears to be dose related with a striking increase when the total dose is over 400 units. Total dose over 400 units should be given with great caution.
Malignant Pleural Effusion: 60 units administered as a single dose bolus intrapleural injection.
Administration: BLEOMYCIN SULFATE may be given by the intramuscular, intravenous, subcutaneous or intrapleural routes.
Intravenous: The contents of the 15 units should be dissolved in 5 mL of Sodium chloride for injection 0.9% and administered slowly over a period of 10 minutes.
Intramuscular or subcutaneous: The BLEOMYCIN SULFATE For Inj. 15 units should be reconstituted with 1-5 mL of sterile water for injection, sodium chloride for injection 0.9%, or sterile bacteriostatic water for injection.
Intrapleural: 60 units of BLEOMYCIN SULFATE is dissolved in 50-100 mL sterile sodium chloride for injection 0.9%. Bleomycin sulfate solutions reconstituted with sodium chloride 0.9% are reported to be stable for four weeks when stored at 2 to 8°C, for two weeks or longer at room temperature, and for 10 days at 37°C.

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.

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

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 sulfate progresses to pulmonary fibrosis, and death.
A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in approximately 1% of lymphoma patients treated with Bleomycin sulfate. Since these reactions usually occur after the first or second dose, careful monitoring is essential after these doses.

Patients with renal impairment.
Patients with pulmonary impairment.
Use in pregnancy & lactation: BLEOMYCIN SULFATE can cause fetal harm when administered to a pregnant woman. It has been shown to be teratogenic in rats (intraperitoneal administration). Pregnant women or women of childbearing potential should be advised to avoid becoming pregnant during therapy with Bleomycin sulfate.
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving Bleomycin sulfate therapy. Safety and effectiveness of Bleomycin sulfate in pediatric patients have not been established.

BLEOMYCIN SULFATE can cause fetal harm when administered to a pregnant woman. It has been shown to be teratogenic in rats (intraperitoneal administration). Pregnant women or women of childbearing potential should be advised to avoid becoming pregnant during therapy with Bleomycin sulfate.
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving Bleomycin sulfate therapy. Safety and effectiveness of Bleomycin sulfate in pediatric patients have not been established.

Pulmonary: Since Bleomycin can cause severe interstitial pneumonia or pulmonary fibrosis, it is necessary to make careful observations and if any change in A-aDo2, PaO2, DLco or any abnormality of the chest roentgenogram is recognized, or if clinical symptoms such as exertional dyspnea or the appearance of rales develop, administration should be immediately halted and appropriate measures must be done.
Idiosyncratic Reactions: Hypotension, mental confusion, fever, chills, and wheezing.
Integument and Mucous Membranes: These consist of erythema, rash, vesiculation, hyperpigmentation, and tenderness of the skin. Hyperkeratosis, nail changes, alopecia, pruritus, and stomatitis have also been reported.
Other: Fever, chills, and vomiting were frequently reported side effects. Anorexia and weight loss are common and may persist long after termination of this medication. Pain at tumor site, phlebitis, and other local reactions were reported infrequently.

Vascular toxicities coincident with the use of Bleomycin sulfate in combination with other antineoplastic agents have been reported rarely. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy (HUS) or cerebral arteritis.
There are also reports of Raynaud's phenomenon occurring in patients treated with Bleomycin sulfate in combination with vinblastine with or without cisplatin or, in a few cases, with Bleomycin sulfate as a single agent.

Store at a temperature not exceeding 30°C.

Cytotoxic Chemotherapy

L01DC01 - bleomycin ; Belongs to the class of other cytotoxic antibiotics. Used in the treatment of cancer.

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