Bleomycin

2927.17

1414.518433

232-925-2

146842

DTXSID1030862|DTXSID2047800

Colorless to yellow powder

L - Antineoplastic and immunomodulating agents

794.66000

-1.89040

white powder

71

H2O: 20 mg/mL

2-8°C

Peritoneal-rat LD50: 168 mg/kg; peritoneal-mouse LD50: 35

Thermal decomposition to release toxic nitrogen oxide gas

Max absorption: 244-248, 289-294 nm (e = 121-148, 102-121.5, 1%, 1 cm) /Bleomycins/|HYGROSCOPIC; MELTING RANGE POORLY DEFINED; SPECIFIC OPTICAL ROTATION (WATER): +12.6 DEG (FRACTION A2); SPECIFIC OPTICAL ROTATION (WATER): +15.0 DEG (FRACTION B2). /SULFATE SALT/

Water soluble

Alcohols and Polyols

3

46-40

53-36/37-45

EC5991990

T

Warehouse ventilated, low temperature and dry

In vitro, bleomycin is inactivated by agents containing sulfhydryl groups, hydrogen peroxide, and ascorbic acid. Bleomycin sulfate sterile powder is stable under refrigeration at 2-8 °C and should not be used after the expiration date is reached.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|For more Disposal Methods (Complete) data for BLEOMYCIN (8 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl bleomycin sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Bleomycin Sulfate/

UMEZAWA H; RECENT STUDIES ON BLEOMYCIN; LLOYDIA 40 (JAN-FEB): 67 (1977). STRUCTURES & PROPERTIES OF BLEOMYCINS ARE DISCUSSED.|BENNETT JM, REICH SD; BLEOMYCIN; ANN INTERN MED 90 (JUN): 945 (1979). REVIEW OF USE OF BLEOMYCIN IN SQUAMOUS CELL CARCINOMAS, TESTICULAR CANCERS, & MALIGNANT LYMPHOMAS & ITS SIDE EFFECTS ARE PRESENTED.|EVANS WE ET AL; CLINICAL PHARMACOLOGY OF BLEOMYCIN AND CISPLATIN; DRUG INTELL CLIN PHARM 16 (6): 448 (1982). A REVIEW WITH 118 REFERENCES OF THE PHARMACOKINETICS AND TOXICITY OF ANTITUMOR DRUGS BLEOMYCIN AND CISPLATIN.|DABROWIAK JC; BLEOMYCIN; ADV INORG BIOCHEM 4: 69 (1982). A REVIEW WITH 122 REFERENCES ON THE PHYSICAL AND CHEM PROPERTIES AND THE BIOCHEMISTRY AND MECHANISM OF ACTION OF BLEOMYCIN.

Flash point data for this compound are not available. It is probably nonflammable. (NTP, 1992)

|Danger|H340 (95.45%): May cause genetic defects [Danger Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 44 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/|For more Preventive Measures (Complete) data for BLEOMYCIN (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

highly toxic

Chemotherapy with bleomycin in combination with other agents is associated with serum enzyme elevations in 10% to 40% of patients and with levels above 5 times ULN in 1% to 7% of patients, depending upon the dose and other agents used. The ALT elevations are usually asymptomatic and transient, resolving within a month of stopping chemotherapy. In many instances, it is difficult to attribute the liver test abnormalities to bleomycin because of the exposure to other potentially hepatotoxic agents. Rare instances of clinically apparent liver injury have been reported in patients receiving bleomycin, but the time to onset and pattern of injury has varied greatly and was usually attributed to other causes such as reactivation of hepatitis B or to sinusoidal obstruction syndrome due to other alkylating agents. Vanishing bile duct syndrome has been described during chemotherapy of Hodgkin disease with bleomycin containing regimens, but this distinctive form of liver injury also occurs in Hodgkin disease patients who are not treated; some instances arising before the diagnosis of lymphoma. The liver histology of bleomycin hepatotoxicity has not been well characterized, but it causes hepatic steatosis in animal models. In a single case report, biliary strictures and a sclerosing cholangitis-like syndrome was described arising several years after intra-arterial embolization of a large hepatic hemangioma with bleomycin.

General anesthetic use in patients previously treated with bleomycin may result in rapid pulmonary deterioration because bleomycin causes sensitization of lung tissue to oxygen; even with concentrations of inspired oxygen considered to be safe, pulmonary fibrosis may develop postoperatively.|Concurrent use of /antineoplastics or radiation therapy/ may result in increased bleomycin toxicity, including bone marrow depression, which is rarely caused by bleomycin alone, and mucosal and pulmonary toxicity...|Cisplatin-induced renal function impairment may result in delayed clearance and bleomycin toxicity even at low doses; caution is recommended because of the frequent combined use of these two agents.|Raynaud's phenomenon has occurred in patients receiving bleomycin and vinblastine, with or without cisplatin, and in a few patients receiving bleomycin as a single agent. Cisplatin-induced hypomagnesemia may be an additional, although not essential, factor associated with its occurrence in patients receiving combination regimens including bleomycin and cisplatin. The cause of Raynaud's phenomenon in these cases, however, is not clearly established and may involve the underlying disease or vascular compromise, bleomycin, vinblastine, hypomagnesemia, or some combination of these factors.|During chemotherapy with bleomycin and etoposide a 28-year-old male, suffering from germ cell cancer, developed acute myocardial infarction. Under treatment with heparin and aspirin the patient revealed no Q-waves in ECG and recovery was without complications. Four weeks after onset of infarction, thallium-201 scintigraphy showed only a small irreversible, posteroseptal perfusion defect; coronary angiography was not performed. The chemotherapy regimen was continued and modified to etoposide as well as cisplatin and ifosfamide without recurrence of cardiac symptoms or ECG changes.

Children of less than 3 years of age have higher total body clearance than in adults, 71 mL/min/sq m versus 51 mL/min/sq m, respectively, following iv bolus administration. Children of more than 8 years of age have comparable clearance as in adults.

... a mixture of cytotoxic glycopeptide antibiotics isolated from a strain og Streptomyces verticillus

While data specific to bleomycin were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

Drug: Abvd|Drug: Abve|Drug: Abve-pc|Drug: Beacopp|Drug: Bep|Drug: Bleomycin|Drug: Copp-abv|Drug: Jeb|Drug: Peb|Drug: Stanfordv

Bleomycin is a cystotoxic antibiotic that is used as an anticancer agent in the therapy of testicular and germ cell cancers, Hodgkin disease, lymphomas and tumors of the head and neck. Therapy with bleomycin in combination with other agents is often associated with mild-to-moderate serum enzyme elevations, but is a rare cause of clinically apparent liver injury.

Antineoplastic Agents

Antibiotics, Antineoplastic; Antibiotics, Glycopeptide; Antimetabolites, Antineoplastic|Bleomycin is indicated in the treatment of squamous cell carcinomas of the head and neck (including the mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingiva, epiglottis, and larynx and paralarynx), cervix, penis, skin and vulva. It is also indicated for treatment of testicular carcinoma (including embryonal cell carcinoma, choriocarcinoma, and teratocarcinoma), esophageal, and thyroid carcinomas. /Included in US product label/|Bleomycin is indicated for the treatment of Hodgkin's and non-Hodgkin's lymphomas. /Included in US product label/|Bleomycin is indicated in the treatment of AIDS-associated Kaposi's sarcoma. /NOT included in US product label/|For more Therapeutic Uses (Complete) data for BLEOMYCIN (12 total), please visit the HSDB record page.

The most serious toxic effect of bleomycin is pulmonary reactions, usually presenting as interstitial pneumonitis, which occurs in approximately 10% of patients receiving the drug. Bleomycin pneumonitis occasionally progresses to pulmonary fibrosis and has resulted in death in approximately 1% of patients receiving the drug. Pulmonary toxicity generally appears to be dose and age related, occurring most frequently in patients older than 70 years of age and those receiving a total dosage of more than 400 units; however, pulmonary toxicity is unpredictable and reportedly has developed in younger patients receiving lower doses (e.g. after a total dosage of less than 200 units). Fatal pulmonary fibrosis occurred in a geriatric patient who received a total dosage of only 20 units of the drug.|Rarely, sudden onset of an acute chest pain syndrome suggestive of pleuropericarditis has been reported during continuous infusions of bleomycin. Improvement of this syndrome may be noted with slower infusion rates of the drug and patients may require analgesics for treatment of pain; total recovery usually occurs after discontinuance of the drug.|In at least one patient, cavitary pulmonary nodules associated with granuloma developed after combination therapy containing bleomycin; spontaneous resolution of these lesions occurred despite continuation of therapy.|Careful monitoring for clinical manifestations and evidence of pulmonary toxicity is required in patients receiving bleomycin. Dosage modification or discontinuance of the drug may be necessary in patients experiencing pulmonary toxicity.|For more Drug Warnings (Complete) data for BLEOMYCIN (28 total), please visit the HSDB record page.

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)

Bleomycin sulfate is not significantly absorbed from the GI tract and the drug must be administered parenterally. Bleomycin is absorbed systemically following intrapleural or intraperitoneal administration. Systemic absorption of 45% has been reported following intrapleural administration of bleomycin.|Bleomycin is rapidly absorbed following either intramuscular (IM), subcutaneous (SC), intraperitoneal (IP) or intrapleural (IPL) administration reaching peak plasma concentrations in 30 to 60 minutes. Systemic bioavailability of bleomycin is 100% and 70% following IM and SC administrations, respectively, and 45% following both IP and IPL administrations, compared to intravenous and bolus administration.|Bleomycin is widely distributed throughout the body with a mean volume of distribution of 17.5 L/sq m in patients following a 15 units/sq m IV bolus dose.|Protein binding of bleomycin is very low (1%).|For more Absorption, Distribution and Excretion (Complete) data for BLEOMYCIN (9 total), please visit the HSDB record page.

Biotransformation is unknow; probably by enzymatic degradation in tissues (based on animal studdies). Tissue enzyme activity varies, which may determine toxicity and antitumor effect of bleomycin... It is not known if any of the metabolites are active.|Bleomycin is inactivated by a cytosolic cysteine proteinase enzyme, bleomycin hydrolase. The enzyme is widely distributed in normal tissues with the exception of the skin and lungs, both targets of bleomycin toxicity. Systemic elimination of the drug by enzymatic degradation is probably only important in patients with severely compromised renal function.

In patients with creatinine clearance exceeding 35 mL/minute, the serum or plasma terminal half-life of bleomycin is about 2 hours. In patients with creatinine clearances less than 35 mL/minute, the terminal half-life of the drug is inversely related to creatinine clearance.|The average steady-state concentration of bleomycin in plasma of patients receiving continuous infusions of 30 units daily for 4-5 days is approx 150 ng/mL, and there is little bound to plasma proteins. Bleomycin disappears from plasma in a biphasic fashion; the initial half-life is about 1.3 hr, & the terminal half-life is approximately 9 hr.

Cytotoxic action of bleomycins results from their ability to cause fragmentation of DNA. Studies in vitro indicate that bleomycin causes accumulation of cells in the G2 phase of the cell cycle, and many of these cells display chromosomal aberrations, incl chromatid breaks, gaps, and fragments, as well as translocations. Bleomycin appears to cause scission of DNA by interacting with oxygen and iron(2+). In the presence of oxygen and a reducing agent, such as dithiothreitol, the metallobleomycin complex becomes activated and functions mechanistically as a ferrous oxidase, transferring electrons from iron(2) to molecular oxygen to produce activated species of oxygen. It has also been shown that metallobleomycin complexes can be activated by reaction with the flavin enzyme, NADPH-cytochrome p450 reductase. Bleomycin binds to DNA through its amino terminal peptide, and the activated complex generates free radicals that are responsible for scission of the DNA chain.|Bleomycin is an antineoplastic antibiotic. The drug is active against gram-positive and gram-negative bacteria and fungi, but its cytotoxicity precludes its use as an anti-infective agent. The precise mechanism(s) of action of bleomycin is not fully known. Several studies in Escherichia coli and HeLa cells suggest that the drug inhibits the incorporation of thymidine into DNA. In these in vitro studies, DNA synthesis was inhibited to a greater extent than was RNA or protein synthesis. Bleomycin also appears to labilize the DNA structure, resulting in scission of both single- and double-stranded DNA. The drug has no immunosuppressive activity in mice.|Bleomycin is classed as an antibiotic but is not used as an antimicrobial agent. Although bleomycin is effective against both cycling and non-cycling cells, it seems to be most effective in the G2 phase of cell division. Its exact mechanism of antineoplastic action is unknown but may involve binding to DNA, inducing lability of the DNA structure, and reduced synthesis of DNA, and to a lesser extent RNA and ptoteins.|When administered into the pleural cavity in the treatment of malignant pleural effusion, /bleomycin/ acts as a sclerosing agent.

SYMPTOMS: Symptoms of exposure to this compound may include mucocutaneous reactions such as mouth ulcerations; skin redness, ulceration and blistering; headache, mental confusion, fever, chills, cough, wheezing, pneumonitis, nausea, vomiting, abdominal pain, hypotension, cardiorespiratory collapse, hair loss, and pulmonary fibrosis. ACUTE/CHRONIC HAZARDS: Toxic: primarily in the skin and lungs. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup or salt water may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Extravasation; immediately stop the infusion and withdraw as much fluid as possible by negative pressure on the syringe. ... Very few specific treatments or antidotes are available. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/

/HUMAN EXPOSURE STUDIES/ Pulmonary toxicity occurs in 10 to 40% of treated patients, usually 4 to 10 weeks after initiation of treatment; approximately 1% of treated patients have died of pulmonary fibrosis. Pulmonary toxicity is age- and dose-related, occurring most frequently in patients over 70 years of age and/or receiving a total dose greater than 400 Units (although) it has been reported with doses as low as 20 to 60 Units. It may be irreversible and fatal; however, there is some evidence that in patients who survive, symptoms and pulmonary function parameters return to normal in approximately 2 years. It occurs at lower doses in patients who have received other antineoplastics or thoracic radiation; mortality may be as high as 10% in patients who have received pulmonary irradiation. A low-dose allergic pneumonitis has also been reported.|/HUMAN EXPOSURE STUDIES/ Mucocutaneous toxicity is the most frequent adverse effect of bleomycin, occurring in at least 50% of patients receiving the drug. Adverse mucocutaneous effects usually are evident with 1 to 3 weeks following the initiation of therapy. Mucocutaneous effects appear to be reversible and related to total dosage, occurring usually after 150 to 200 units of bleomycin have been administered. Occasionally, mucocutaneous toxicity may necessitate discontinuation of drug or reduction of dosage.|/HUMAN EXPOSURE STUDIES/ Early clinical trials and isolated case reports suggest that bleomycin-induced acute hypersensitivity reactions occur in 1% of patients with lymphoma and <0.5% of those with solid tumors. The reactions are mainly characterized by high-grade fever, chills, hypotension, and in a few cases, cardiovascular collapse, which can lead to death. The exact mechanism of these reactions is unclear, but is thought to be related to the release of endogenous pyrogens from the host cells. Evidence does not suggest any correlation between doses and the onset or severity of the reactions. Supportive care, including hydration, steroids, antipyretics, and antihistamines, may resolve the symptoms. However, it may not completely prevent recurrences. The incidence of acute hypersensitivity or hyperpyrexic reactions associated with bleomycin is very low, but the reaction is potentially fatal. Clinicians should monitor their patients for any signs and symptoms of acute hyperpyrexic reactions during bleomycin administration. Since the onset of the reactions can occur with any dose of bleomycin and at any time, routine test dosing does not seem to predict when drug reactions may occur.|/SIGNS AND SYMPTOMS/ The main reported side effect with intralesional use is local burning or pain within 24 to 48 hours after injection. Blackening and eschar at the site of the lesion within 1 or 2 weeks and healing usually occurs within 2 to 3 weeks without scarring. Cases of urticaria, nail loss, and Raynaud's phenomenon have also been reported.|For more Human Toxicity Excerpts (Complete) data for BLEOMYCIN (20 total), please visit the HSDB record page.

Bellon, Bléomycine

Bleomycin sulfate (blenoxane) is available as lyophilized powder in 15 unit vials.|Parenteral injection 15 units (of bleomycin) Blenoxane and 30 units (of bleomycin) Blenoxane /manufactured by/ Bristol-Myers Squibb. /Generic preparation/: Bleomycin Sulfate for injection /manufactured by/ Bedford, Mayne, Sicor.|Blenoxane; Bleo (sulfate) /Bleomycins/

The drug is employed clinically is a mixture of copper-chelating glycopeptides that consists predominantly of 2 closely related agents, bleomycin A2 & bleomycin B2. The various bleomycins differ only in their terminal-amine moiety...and the addition of various amines to fermentation broths have made possible the preparation of more than 200 different congeners.|The molecule is exceedingly complex, but synthesis was achieved in 1982.

(57)COBALT WAS USED AS TRACER IN RADIOIMMUNAOASSAY FOR BLEOMYCIN. LEVELS DOWN TO 0.025 UG/ML CAN BE DETERMINED.|Analyte: bleomycin sulfate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /bleomycin sulfate/|Analyte: bleomycin sulfate; matrix: chemical purity; procedure: cylinder-plate method with comparison to standards /bleomycin sulfate/|Analyte: bleomycin sulfate; matrix: pharmaceutical preparation (solid for injection); procedure: cylinder-plate method with comparison to standards (chemical purity) /bleomycin sulfate/|For more Analytic Laboratory Methods (Complete) data for BLEOMYCIN (7 total), please visit the HSDB record page.

A RADIOIMMUNOASSAY FOR BLEOMYCIN IN HUMAN BLOOD IS DESCRIBED.|A HIGH PRESSURE LIQ CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF BLEOMYCIN A2 IN PLASMA IS DESCRIBED.|A SENSITIVE AND SPECIFIC ENZYME IMMUNOASSAY FOR BLEOMYCIN IN TISSUES OF RATS IS DESCRIBED.|Analyte: bleomycin sulfate; matrix: blood (plasma), hepatocyte suspension; procedure: high-performance liquid chromatography with fluorescence detection at 297 nm (excitation) and 355 nm (emission); limit of detection: 70 ng/mL /bleomycin sulfate/

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