Daunorubicin

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/

Daunorubicin hydrochloride powder for injection should be stored at 15-30 °C, protected from light, and stored in the carton until time of use.

Commercially available daunorubicin hydrochloride injection should be protected from light in the carton until time of use and refrigerated at 2-8 °C. Following further dilution in 0.9% sodium choride injection, resultant solutions are stable for 24 hours at room temperatures of 15-30 °C; these solutions contain no preservatives, and unused portions should be discarded after this period.

Commercially available daunorubicin citrate liposomal injection should be refrigerated at 2-8 °C and protected from light and freezing; the shelf-life of the injection is 24 weeks when stored as recommended. When diluted as directed with dextrose 5% injection, solutions of daunorubicin citrate liposomal injection are stable for up to 6 hours when refrigerated at 2-8 °C.

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/

/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 contain

/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/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U059, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

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

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for DAUNORUBICIN (28 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

/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/

Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity.

Use of Cerubidine in a patient who has previously received doxorubicin increases the risk of cardiotoxicity. Cerubidine should not be used in patients who have previously received the recommended maximum cumulative doses of doxorubicin or Cerubidine. Cyclophosphamide used concurrently with Cerubidine may also result in increased cardiotoxicity.

Daunorubicin may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse daunorubicin-induced hyperuricemia because of risk or uric acid nephropathy with uricosuric antigout agents.

Leukopenic and/or thrombocytopenic effects of daunorubicin may be increased with concurrent or recent therapy /with blood dyscrasia-causing medications/ if these medications cause the same effects; dosage adjustment of daunorubicin, if necessary, should be based on blood counts.

For more Interactions (Complete) data for DAUNORUBICIN (11 total), please visit the HSDB record page.

Chemotherapy with daunorubicin in combination with other agents is associated with serum enzyme elevations in a proportion of patients depending upon the dose and other agents used. ALT elevations during daunorubicin therapy are usually asymptomatic and transient and may resolve without dose modification. In many instances, it is difficult to attribute the liver test abnormalities to daunorubicin, because of the exposure to other potentially hepatotoxic agents. There have been no convincing instances of acute, clinically apparent idiosyncratic liver injury with jaundice associated with daunorubicin therapy. However, high doses of daunorubicin given in combination with other antineoplastic agents have been linked to cases of sinusoidal obstruction syndrome, typically presenting with right upper quadrant pain 10 to 30 days after the infusion, followed by weight gain, ascites and liver test abnormalities. Fatalities due to hepatic failure have occurred, but most patients recover within 1 to 3 months of onset.；Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

Daunorubicin cause both dose-limiting and non-limiting adverse effects. Some of the common and most serious dose-limiting adverse effects include bone marrow suppression and cardiotoxicity. Bone marrow suppression usually occurs in all patients given the therapeutic dose of daunorubicin; therefore, it should be used cautiously in patients with pre-existing bone marrow suppression. It usually manifests as severe infections or hemorrhage.；Daunorubicin can cause potential cardiac toxicity, especially in children and the elderly. Pre-existing heart disease and concomitant treatment with other cytotoxic agents or radiotherapy involving the field of the heart can enhance the risk of developing daunorubicin-induced cardiotoxicity. It usually presents with new-onset congestive heart failure, although rarely it can present as myocarditis or pericarditis. In adults, the cardiac toxic effects are usually seen after a cumulative dose exceeding 400 to 550 mg/m^2, although it may also occur on doses as low as 200 mg/m^2. Symptomatic heart failure can occur during and even months to years later after the cessation of the therapy. Therefore, serial electrocardiograms (EKG) and echocardiograms are indicated before the initiation and with successive chemotherapy sessions with daunorubicin.；Other more common dose non-limiting adverse effects include reversible alopecia, mucositis, nausea, vomiting, and local skin necrosis, cellulitis, or induration due to extravasation of the drug into the tissues.；Rarely it causes secondary leukemias, hypersensitivity reactions, urticaria, local dermatitis, tumor lysis syndrome, and hyperuricemia.

Daunorubicin causes cardiotoxicity by forming complexes with topoisomerase IIb enzyme in cardiomyocytes. This activity is the same as when the drug forms complexes with topoisomerase IIa in tumor cells and can result in mitochondrial damage with subsequent myocardial cell death. Dexrazoxane is a cardio-protectant agent. Research has shown it to decrease the incidence and severity of cardiotoxicity when given from the first dose of anthracyclines without reducing the effectiveness of the chemotherapeutic agent. It acts by inhibiting the isomer of topoisomerase and decrease the free radical damage by chelating free iron. It is administered intravenously in a ratio of 10 to 1 of dexrazoxane: daunorubicin. Cardiac monitoring is still a recommendation despite concurrent therapy, and if a patient develops a decline in the left ventricular function or develops symptomatic heart failure, treatment should discontinue immediately.

Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Daunorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=20830-81-3]

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/

/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/

/SIGNS AND SYMPTOMS/ Hemorrhagic enterocolitis, renal tubular damage, and hematuria, nausea, anorexia, ... vomiting, abdominal pain, mucositis, ... rash, and lymphoid atrophy also occur /in patients following iv infusion/.

/SIGNS AND SYMPTOMS/ Toxic manifestations of daunorubicin incl bone marrow depression, stomatitis, alopecia, gastrointestinal disturbances, and dermatological manifestations. Cardiac toxicity is peculiar adverse effect ... characterized by tachycardia, arrhythmias, dyspnea, hypotension, and congestive failure unresponsive to digitalis.

/SIGNS AND SYMPTOMS/ Myelosuppression is dose limiting and severe aplasia may develop. Leukopenia ... more significant than thrombocytopenia ... Febrile reactions ... may occur ... Severe local tissue necrosis may develop if extravasation occurs ... Causes transient red discoloration of urine, which is of no clinical significance. /IV; HCl salt/

/SIGNS AND SYMPTOMS/ Daunorubicin was reported to cause abnormal nail pigmentation /identified as/ transverse brown-black bands on the nail plate. /From table/

For more Human Toxicity Excerpts (Complete) data for DAUNORUBICIN (19 total), please visit the HSDB record page.

Hazard Traits - Carcinogenicity；Authoritative List - IARC Carcinogens - 2B; Prop 65；Report - regardless of intended function of ingredient in the product

5,12-Naphthacenedione, 8-acetyl-10-(3-amino-2,3,6-trideoxy-.alpha.-L-lyxo-hexopyranosyl)oxy-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8S,10S)-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

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

U059; As stipulated in 40 CFR 261.33, when daunomycin, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV.D.3.b).

An anti-mitotic agent used in cancer chemotherapy; [HSDB]

Antimitotic agent in cancer chemotherapy (non-USA use).

Therapeutic Category: Antineoplastic

MEDICATION

For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Daunorubicinone

Daunorubicinol

13-dihydrodaunorubicinone

Doxorubicin

For more Impurities (Complete) data for DAUNORUBICIN (6 total), please visit the HSDB record page.

(1977) Not produced commercially in USA

(1979) Not produced commercially in USA

Isolated from fermentation broths of Streptomyces peucetius.

Daunorubicin is obtained from cultures of Streptomyces caeruleorubidus and Streptomyces peucetius, which occur in soil.

Acetyladriamycin

Cerubidin

Cerubidine; Daunoblastina; Ondena. /Daunorubicin hydrochloride/.

Daunarubicinum

For more Formulations/Preparations (Complete) data for DAUNORUBICIN (19 total), please visit the HSDB record page.