Daunorubicin

527.52

527.52

245-723-4

ZS7284E0ZP

756717

DTXSID7022883

C62091

Reddish needles|Thin, red needles

L01DB02|L - Antineoplastic and immunomodulating agents

186

0.1

1.6±0.1 g/cm3

208-209 °C

190 deg C, decomposes

419.5±32.9 °C

1.692

6.27e-01 g/L

Commercially available daunorubicin citrate liposomal injection should be refrigerated at 2-8 deg 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 deg C.

9.4X10-15 mm Hg at 25 deg C

Oral-Rat  LD50 336  mg/kg; Oral-Mouse LD50: 205 mg/kg

Open flame, heat, oxidant is combustible; burning emits nitrogen oxides to stimulate smoke

Henry's Law constant = 2.18X10-13 atm-cu m/mol at 26 °C

pKa = 7.85

222.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

The aglycone can be reduced by sodium borohydride; subsequent periodate oxidation yields benzaldehyde.|Aqueous solutions are stable for one month at 5 °C; unstable at higher temperatures or at acid or alkaline pH's.|Hydroxyl radical reaction rate constant = 1.4X10-10 cu cm/molec-sec at 25 °C (est)

No rapid reaction with air. No rapid reaction with water.

Amines, Phosphines, and Pyridines

III

6.1(b)

3249

R3249

The warehouse is ventilated, low temperature and dry; lightly loaded and unloaded, stored separately from oxidants and acids

Following reconstitution as directed, daunorubicin hydrochloride solutions are stable for 24 hours at room temperature or 48 hours when refrigerated at 2-8 deg C. The reconstituted solution should be protected from sunlight. Daunorubicin hydrochloride is unstable in solutions with a pH greater than 8; decomposition is indicated by a color change from red to blue-purple.

P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, P501

H301

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.

Caution: The only fluid which may be mixed with DaunoXome is D5W; DaunoXome must not be mixed with saline, bacteriostatic agents such as benzyl alcohol, or any other solution.|A precipitate may form immediately if daunorubicin hydrochloride solution is mixed with heparin sodium injection or dexamethasone sodium phosphate injection. The manufacturer states that daunorubicin hydrochloride injection should not be mixed with other drugs or heparin.

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/

Weisburger EK; Bioassay Program for Carcinogenic Hazards of Cancer Chemotherapeutic Agents; Cancer 40: 1935-49 (1977). Route: intraperitoneal injection; Species: rats and mice.

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, and P501|Aggregated GHS information provided by 52 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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/|For more Personal Protective Equipment (PPE) (Complete) data for DAUNORUBICIN (6 total), please visit the HSDB record page.

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 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": 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": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/|/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/

U059; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

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).

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).

highly toxic

LD50=20 mg/kg (mice, IV); LD50=13 mg/kg (rat, IV)

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.

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.

LD50 Rat ip 20 mg/kg|LD50 Rat iv 13 mg/kg|LD50 Mouse oral 105 mg /kg|LD50 Mouse uo 2500 ug/kg|For more Non-Human Toxicity Values (Complete) data for DAUNORUBICIN (6 total), please visit the HSDB record page.

Recognition and analysis of distinct mechanisms by which primaquine and other hemolytic drugs activate the hexose monophosphate shunt (HMS) have suggested a hitherto unsuspected pharmacogenetic interaction between daunorubicin metabolism and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Because this deficiency is very common, and because anthracyclines are indispensable antitumor antibiotics that are biotransformed mainly by carbonyl reductase, we have compared the reductase-mediated conversion of daunorubicin to daunorubicinol and the conversion of doxorubicin to doxorubicinol in G6PD-deficient and nondeficient erythrocytes. We found that even without G6PD deficiency, the HMS dehydrogenases selectively limited daunorubicin metabolism, as contrasted with that of doxorubicin. The milder GdA- variety of G6PD deficiency restricted the biotransformation of daunorubicin at therapeutic levels, in hemolysates and intact erythrocytes, within 15 minutes, for at least 24 hours. The bioconversion defect was even more severe in Gd Mediterranean G6PD deficiency. Primaquine aldehyde competed with daunorubicin as a substrate for carbonyl reductase. These studies show that HMS dehydrogenase activity controls carbonyl reductase-dependent biotransformation. New issues arise concerning possible effects of G6PD deficiency on the oncolytic and toxic properties of anthracyclines that are effective substrates for carbonyl reductase and also on non-xenobiotic reactions catalyzed by this enzyme.

97% binding-albumin

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

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The danger to health-care personnel from handling a hazardous drug stems from a combination of its inherent toxicity and the extent to which workers are exposed to the drug in the course of carrying out their duties. This exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/

For remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.|Treatment of acute myeloid leukaemia|Drug: Daunorubicinhydrochloride

Daunorubicin is an anthracycline antibiotic that has antineoplastic activity and is used in the therapy of acute leukemia and AIDS related Kaposi sarcoma. Daunorubicin is associated with a low rate of transient serum enzyme and bilirubin elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury with jaundice.

Antineoplastic Agents

Antibiotics, Antineoplastic|Cerubidine in combination with other approved anticancer drugs is indicated for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. /Included in US product label/|DaunoXome is indicated as a first line cytotoxic therapy for advanced HIV-associated Kaposi's sarcoma. DaunoXome is not recommended in patients with less than advanced HIV-related Kaposi's sarcoma. /Included in US product label/|An 8-month-old baby with symptoms of Letterer-Siwe's disease responded dramatically after a 5-day course of daunorubicin, 1 mg per kg body-weight daily. A second course was given 2 weeks later.

Cerubidine must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration.|Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/sq m in adults, 300 mg/sq m in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age.|Cardiac function should be monitored regularly in patients receiving DaunoXome (daunorubicin citrate liposome injection) because of the potential risk for cardiac toxicity and congestive heart failure. Cardiac monitoring is advised especially in those patients who have received prior anthracyclines or who have pre-existing cardiac disease or who have had prior radiotherapy encompassing the heart.|Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage.|For more Drug Warnings (Complete) data for DAUNORUBICIN (45 total), please visit the HSDB record page.

Daunorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Daunorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)|Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II. (See all compounds classified as Topoisomerase II Inhibitors.)

Twenty-five percent of an administered dose of daunorubicin hydrochloride is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.|Note: Liposomal encapsulation can substantially affect a drug's functional properties relative to those of the unencapsulated drug. In addition, different liposomal drug products may vary from one another in the chemical composition and physical form of the liposomes. Such differences can substantially affect the functional properties of liposomal drug products.|Encapsulation of daunorubicin citrate in liposomes substantially alters the pharmacokinetics of the drug relative to conventional iv formulations (ie, nonencapsulated drug) with resultant decreased distribution into the peripheral compartment, increased distribution into Kaposi's lesions, and decreased plasma clearance|Daunorubicin hydrochloride is extremely irritating to tissues and, therefore, must be administered iv. Following iv infusion of a single 40-mg/sq m dose of liposomal daunorubicin citrate as a liposomal injection in patients with AIDS-related Kaposi's sarcoma, mean peak plasma daunorubicin (mostly bound to liposomes) concentrations are approximately 18 mug/mL following a 30-60 minute infusion. Peak plasma concentrations of daunorubicin are higher following iv administration of liposomal daunorubicin citrate than those attained following iv administration of conventional (nonencapsulated) daunorubicin hydrochloride.|In one study in patients with disseminated malignancies receiving a single 80-mg/sq m iv dose of nonencapsulated daunorubicin, peak plasma concentrations of the drug were 0.4 ug/mL while in patients with solid tumors (including those with Kaposi's sarcoma) who received a single 80-mg/sq m iv dose of liposomal daunorubicin, peak plasma concentrations of daunorubicin were about 44 ug/mL (about 100-fold greater than those receiving a comparable dose of the nonencapsulated drug); area under the plasma concentration-time curve (AUC) was about 36-fold greater than that observed with conventional daunorubicin hydrochloride. Following iv administration of liposomal daunorubicin, peak plasma concentrations and AUCs of daunorubicin generally increase linearly with increasing doses (at doses of 10-80 ug/mL).|For more Absorption, Distribution and Excretion (Complete) data for DAUNORUBICIN (18 total), please visit the HSDB record page.

Hepatic|Daunorubicin hydrochloride is extensively metabolized in the liver and other tissues, mainly by cytoplasmic aldo-keto reductases, producing daunorubicinol, the major metabolite which has antineoplastic activity. Approximately 40% of the drug in the plasma is present as daunorubicinol within 30 minutes and 60% in 4 hours after a dose of nonencapsulated daunorubicin.|Daunorubicinol has been detected only in low concentrations in the plasma following iv administration of daunorubicin citrate liposomal injection. In patients with AIDS-associated Kaposi's sarcoma receiving iv administration of liposomal daunorubicin doses of 40 mg/sq m, the AUC of daunorubicinol represented only 2% of the total daunorubicin AUC. Additional metabolism by reductive cleavage of the glycosidic bond produces aglycones, which have little or no cytotoxic activity and are demethylated and conjugated with sulfate and glucuronide by microsomal enzymes.|Metabolites identified in human urine are daunorubicinol, daunorubicinol aglycone, desmethyldeoxydaunorubicinol aglycone, desmethyldeoxyrubicinol aglycone-4-o-sulfate, desmethyloxydaunorubicinol aglycone-4-o-glucuronide, and deoxydaunorubicinol aglycone glucuronide.|Extensively metabolized, initially to active alcohol metabolites; further metabolized by liver microsomes to inactive aglycones and demethylated glucuronide and sulfate conjugates.

18.5 hours|Following rapid iv administration of conventional daunorubicin hydrochloride injection, total plasma concentrations of daunorubicin and its metabolites decline in a triphasic manner, and plasma concentrations of unchanged daunorubicin decline in a biphasic manner.|The plasma half-life of nonencapsulated daunorubicin averages 45 minutes in the initial phase and 18.5 hours in the terminal phase. By 1 hour after administration of nonencapsulated daunorubicin, the predominant form of the drug in plasma is the active metabolite daunorubicinol, which has an average terminal plasma half-life of 26.7 hours.|The apparent elimination half-life of DaunoXome (daunorubicin citrate liposome injection) is 4.4 hours, far shorter than that of daunorubicin, and probably represents a distribution half-life.

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.|Daunorubicin is an antineoplastic antibiotic. Daunorubicin has antimitotic and cytotoxic activity. Daunorubicin forms a complex with DNA by intercalation between base pairs. By stabilizing the complex between DNA and topoisomerase II, daunorubicin inhibits the activity of this enzyme, resulting in single-strand and double-strand breaks in DNA. Daunorubicin also may inhibit polymerase activity, affect regulation of gene expression, and be involved in free radical damage to DNA. Although daunorubicin is maximally cytotoxic in the S phase, the drug is not cycle-phase specific. Daunorubicin also has antibacterial and immunosuppressive properties.|Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms of anthracycline action involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a major critical factor that determines anthracycline resistance. Natural product, daunorubicin a toxic analogue of anthracycline is reduced to less toxic daunorubicinol by the AKR1B10, enzyme, which is overexpressed in most cases of smoking associate squamous cell carcinoma (SCC) and adenocarcinoma. In addition, AKR1B10 was discovered as an enzyme overexpressed in human liver, cervical and endometrial cancer cases in samples from uterine cancer patients. Also, the expression of AKR1B10 was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma in cervical cancer and estimated to have the potential as a tumor intervention target colorectal cancer cells (HCT-8) and diagnostic marker for non-small-cell lung cancer. This article presents the mechanism of daunorubicin action and a method to improve the effectiveness of daunorubicin by modulating the activity of AKR1B10.|... In the present study using the ATP depleting agents cyanide, azide, or dinitrophenol to inhibit energy dependent transport processes, /investigators/ observed even larger increases in daunorubicin accumulation than were seen with CsA. Similar patterns were seen in a wide range of P-gp negative human cancer cell lines. Also the observed cyanide effect did not correlate with the expression of mRNA for multidrug resistance-associated protein (MRP), the only other member of the ABC family of membrane transporters that is known to be capable of effluxing daunorubicin. Thse results suggest that daunorubicin accumulation in many cases of AML is modulated by one or more novel energy-dependent processes that are distinct from P-gp or MRP. /The authors/ speculate that this novel drug transport mechanism(s) may influence the response of AML patients to daunorubicin and other therapeutic agents.|Inhibits DNA synthesis and blocks DNA-directed RNA polymerase. It can prevent cell division in doses that do not interfere with nucleic acid synthesis.

Daunorubicinone|Daunorubicinol|13-dihydrodaunorubicinone|Doxorubicin|For more Impurities (Complete) data for DAUNORUBICIN (6 total), please visit the HSDB record page.

Four adult patients who suffered anthracycline extravasation ... were treated with a regimen of ice, local glucocorticoid injection, and dimethylsulfoxide (DMSO) 55%-99% applied topically every 2-4 hr after extravasation for a minimum of 3 days. In all four cases, pain and erythema resolved within 2 days; in no case did tissue necrosis or skin ulceration occur. /Anthracycline/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/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.

Cerubidine

Acetyladriamycin|Cerubidin|Cerubidine; Daunoblastina; Ondena. /Daunorubicin hydrochloride/.|Daunarubicinum|For more Formulations/Preparations (Complete) data for DAUNORUBICIN (19 total), please visit the HSDB record page.

Daunorubicin is a glycoside formed by a tetracyclic aglycone, daunomycinone, and an amino sugar, daunosamine, 3-amino-2,3,6-trideoxy-l-lyxo-hexose.

Analyte: daunorubicin hydrochloride; matrix: chemical identification; infrared absorption spectrophotometry of a potassium bromide dispersion with comparison to standards /Daunorubicin hydrochloride/|Analyte: daunorubicin hydrochloride; matrix: chemical identification; procedure: retention time of the main peak of the chromatogram with comparison to standards /Daunorubicin hydrochloride/|Analyte: daunorubicin hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /Daunorubicin hydrochloride/|For more Analytic Laboratory Methods (Complete) data for DAUNORUBICIN (8 total), please visit the HSDB record page.

Analyte: daunorubicin hydrochloride; matrix: pharmaceutical preparation (injection solution); procedure: retention time of the major peak of the liquid chromatogram with comparison to standards (chemical identification) /Daunorubicin hydrochloride/|Analyte: daunorubicin hydrochloride; matrix: pharmaceutical preparation (injection solution); procedure: liquid chromatography with ultraviolet detection at 254 nm and comparison to standards (chemical purity) /Daunorubicin hydrochloride/|Analyte: daunorubicin; matrix: cell suspension; procedure: high-performance liquid chromatography with ultraviolet detection at 237 nm; limit of detection: 2 pmol|Analyte: daunorubicin; matrix: blood (plasma), urine; procedure: high-performance liquid chromatography with fluorescence detection at 480 nm (excitatory) and 560 nm (emission)|For more Clinical Laboratory Methods (Complete) data for DAUNORUBICIN (17 total), please visit the HSDB record page.

Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Polyketides [PK] -> Aromatic polyketides [PK13] -> Anthracyclinones [PK1305]