BLEOMYCIN SULFATE

Chemistry - An antibiotic antineoplastic agent, bleomycin sulfate is obtained from Streptomycesverticullis. It occurs as a cream colored, amorphous powder that is very soluble in water andsparingly soluble in alcohol. After reconstitution, the pH of the solution ranges from 4.5-6.
Bleomycin is assayed microbiologically. One unit of bleomycin is equivalent to one mg of thereference Bleomycin A2 standard.

Storage, Stability, Compatibility

Powder for injection should be kept refrigerated. After reconstituting with (sterile saline, water, or dextrose) the resulting solution is stable for 24 hours.
Bleomycin is less stable in dextrose solutions than in saline. After reconstituting with normal saline, bleomycin is reportedly stable for at least two weeks at room temperature and for 4 weeks whenrefrigerated. However, since there are no preservatives in the resulting solution, the product isrecommended to be used with 24 hours.
Bleomycin sulfate is reported to be compatible with the following drugs: amikacin sulfate, cisplatin, cyclophosphamide, dexamethasone sodium phosphate, diphenhydramine HCl, doxorubicin, heparin sodium, metoclopramide HCl, vinblastine sulfate, and vincristine sulfate. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information.

Pharmacology - BLEOMYCIN SULFATE

Bleomycin is an antibiotic that has activity against a variety of gram-negative andgram-positive bacteria as well as some fungi. While its cytotoxicity prevents it from being clinical yuseful as an antimicrobial, it is useful against a variety of tumors in small animals. Its exactmechanism of action is unknown, but it is possible it inhibits the incorporation of thymidine into
DNA. Bleomycin also appears to labilize DNA, thereby splitting both single stranded and doublestranded DNA.
Uses, Indications - Bleomycin has been used as adjunctive treatment of lymphomas, squamous cellcarcinomas, teratomas, and nonfunctional thyroid tumors in both dogs and cats.

Pharmacokinetics - BLEOMYCIN SULFATE

Bleomycin is not appreciably absorbed from the gut and thus must be administered parenterally. It is mainly distributed to the lungs, kidneys, skin, lymphatics and peritoneum. In patients with normal renal function, terminal half life is about 2 hours. In humans, 60-70% of a dose is excreted as active drug in the urine.

Contraindications, Precautions, Reproductive Safety

Because bleomycin is a toxic drug witha low therapeutic index, it should be used only by those with the facilities to actively monitor thepatient and deal with potential complications. The drug should be used very cautiously in patientswith significant renal insufficiency or pulmonary disease (not due to tumor). Bleomycin can beteratogenic, it should only be used in pregnant animals when the owners accept the associated risks.

Adverse Effects, Warnings

Toxicity falls into two broad categories: acute and delayed. Acutetoxicities include fever, anorexia, vomiting, and allergic reactions (including anaphylaxis). Delayedtoxic effects include dermatologic effects (e.g., alopecia, rashes, etc.), stomatitis, pneumonitis andpulmonary fibrosis. These latter two effects have been associated with drug induced fatalities.
Unlike many other antineoplastics, bleomycin does not usually cause bone marrow toxicity, butthrombocytopenia, leukopenia and slight decreases in hemoglobin levels are possible. Renal andhepatotoxicity are also potentially possible.

Overdosage, Acute Toxicity

No specific information located. Because of the toxicity of the drug, it is important to determine dosages carefully.

Drug Interactions

Use of general anesthetics in patients treated previously with bleomycinshould be exercised with caution. Bleomycin sensitizes lung tissue to oxygen (even to concentrations of inspired oxygen considered to be safe) and rapid deterioration of pulmonary functionwith post-operative pulmonary fibrosis can occur. Prior chemotherapy with other agents orradiation therapy can lead to increased hematologic, mucosal and pulmonary toxicities withbleomycin therapy. There are some reports that digoxin or phenytoin serum levels may be decreased by combination chemotherapy; the significance of these interactions are in question.