카르무스틴

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.

Carmustine powder must be refrigerated at 2 - 8 °C. Both the powder and its solutions must be protected from light.

Carmustine wafers must be stored at a temperature of -20 °C or less. The aluminum foil laminate pouches containing each carmustine wafer should not be opened until immediately prior to the implantation procedure. Unopened foil pouches may be kept at ambient room temperature for up to 6 hours at a time.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Evacuate personnel to safe areas. Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.

/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 "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing 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.

Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state, and local environmental regulations. Contact a licensed professional waste disposal service to dispose of this material.

SRP: 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/

For more Disposal Methods (Complete) data for Carmustine (14 total), please visit the HSDB record page.

Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. Choose body protection according to the amount and concentration of the dangerous substance at the work place.

/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/

For more Preventive Measures (Complete) data for Carmustine (30 total), please visit the HSDB record page.

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)

Handle with gloves. Face shield and safety glasses.

Wear self contained breathing apparatus for fire fighting if necessary.

Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

/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/

For more Personal Protective Equipment (PPE) (Complete) data for Carmustine (9 total), please visit the HSDB record page.

In patients receiving carmustine and phenytoin, serum concentrations of phenytoin may be decreased. In patients receiving carmustine therapy, serum concentrations of phenytoin should be monitored carefully and dosage adjustments made as necessary.

Qualitative and quantitative changes in tear films leading to damage of the corneal and conjunctival epithelium have been reported in patients receiving high doses of carmustine and mitomycin.

Cimetidine may potentiate the myelosuppressive effects (e.g., neutropenia, agranulocytosis) of myelosuppressive drugs (e.g., alkylating agents, antimetabolites) or therapies (e.g., radiation). Concomitant cimetidine therapy has been reported to potentiate the neutropenic and thrombocytopenic effect of carmustine alone or combined with radiation therapy.

Mild and transient elevations in serum aminotransferase levels are found in up to 25% of patients treated with carmustine. Because carmustine is typically given in combination with other agents, its role in causing these serum enzyme elevations is not always clear. The abnormalities are generally transient, do not cause symptoms and do not require dose modification. Clinically apparent liver injury from carmustine has been limited to a small number of cases of cholestatic hepatitis and more frequent instances of sinusoidal obstruction syndrome, reported mostly with its use in high doses or as a conditioning agent in preparation for hematopoietic cell transplantation. The onset of sinusoidal obstruction syndrome is usually within two to three weeks of the myeloablation and is characterized by a sudden onset of abdominal pain, weight gain, ascites, marked increase in serum aminotransferase levels (and LDH), and subsequent jaundice and hepatic dysfunction. The severity of sinusoidal obstruction syndrome varies from a transient, self-limited injury to acute liver failure. The diagnosis of sinusoidal obstruction syndrome is usually based on clinical features of tenderness and enlargement of the liver, weight gain, ascites and jaundice occurring within 3 weeks of chemotherapy. Liver biopsy is diagnostic but often contraindicated, because of severe thrombocytopenia after hematopoietic cell transplantation.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 150(SRC), determined from a structure estimation method(2), indicates that carmustine is expected to have high mobility in soil(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization of carmustine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.8X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Carmustine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-4 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 150(SRC), determined from a structure estimation method(2), indicates that carmustine is expected to adsorb to suspended solids and sediment(SRC). However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 4.8X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 5(SRC), from its log Kow of 1.53(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Carmustine is an alkylating agent that may hydrolyze under environmental conditions(4). Biodegradation data were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), carmustine, which has an estimated vapor pressure of 2.9X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase carmustine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4.4 days(SRC), calculated from its rate constant of 3.6X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase carmustine may be removed from the air by wet or dry deposition(SRC). Carmustine contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Carmustine causes cross-links in DNA and RNA, leading to the inhibition of DNA synthesis, RNA production and RNA translation (protein synthesis). Carmustine also binds to and modifies (carbamoylates) glutathione reductase. This leads to cell death.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 150 can be estimated to be carmustine(SRC). According to a classification scheme(2), this estimated Koc value suggests that carmustine is expected to have high mobility in soil. However, by analogy to N-nitroso-N-ethylurea which exhibited a hydrolysis half-life of 47 minutes at pH 9(3), adsorption may be precluded by hydrolysis(SRC).

/SIGNS AND SYMPTOMS/ Pulmonary toxicity, including acute or delayed onset of pulmonary fibrosis causing death, has occurred in patients receiving systemic carmustine therapy. Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis occurring 9 days to 43 months following treatment has been reported in patients receiving carmustine or related nitrosoureas. Most reported cases of pulmonary toxicity have occurred in patients receiving prolonged carmustine therapy with total doses exceeding 1400 mg/sq m; however, pulmonary fibrosis has occurred with lower total doses. Other risk factors include prior history of pulmonary disease and duration of carmustine therapy. Pulmonary toxicity occasionally has been rapidly progressive and/or fatal.

/SIGNS AND SYMPTOMS/ In a randomized trial, encephalopathy, sometimes fatal, was reported in patients receiving intra-arterial carmustine.

/SIGNS AND SYMPTOMS/ ... bis(chloroethyl) nitrosourea is associated with acute nonlymphocytic leukemia following its use with other anticancer therapies in the treatment of previously existing cancer.

/SIGNS AND SYMPTOMS/ Human systemic effects by parenteral, intravenous, and possibly other routes: nausea or vomiting, reduced white blood cell and blood platelet counts, bone marrow damage, and potentially fatal respiratory system effects, including lung fibrosis, dyspnea, and cyanosis.

For more Human Toxicity Excerpts (Complete) data for Carmustine (26 total), please visit the HSDB record page.

Bischloroethyl nitrosourea (BCNU) (Carmustine)

Group 2A: Probably carcinogenic to humans

Volume 26: (1981) Some Antineoplastic and Immunosuppressive Agents

1987

1987

2A, probably carcinogenic to humans. (L135)

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

carmustine

BiCNU®

Antineoplastic agents

3

less-DILI-concern drugs

An estimated BCF of 5 was calculated in fish for carmustine(SRC), using a log Kow of 1.53(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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

Medication to treat cancer of the lymph system, cancerous brain tumors, and a certain type of bone marrow cancer

THERAPEUTIC CATEGORY: Antineoplastic

For the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas.

Carmubris

Carmustin

Nitrumon

Local: Implants: 7.7 mg (of carmustine per wafer) Gliadel Wafer (MGI Pharma).

Parenteral: For injection, for IV infusion: 100 mg BiCNU (Bristol-Myers Squibb).

An antineoplastic nitrosourea

... designed to deliver carmustine directly into the surgical cavity created when a brain tumor is resected /Gliadel wafer/