Mithramycin

1085.15

1085.15

232-455-8

NIJ123W41V

DTXSID6023492

C658

YELLOW, CRYSTALLINE POWDER SHOWING BIREFRINGENCE

L - Antineoplastic and immunomodulating agents

29419090

358.20000

1.29

Red to brown Powder

1.1576 (rough estimate)

180-183 °C

761.72°C (rough estimate)

327.4±27.8 °C

1.6500 (estimate)

Sol in lower alcohols, acetone, ethyl acetate, water. Moderately sol in chloroform. Slightly sol in ether, benzene.|1 G SOL IN LESS THAN 200 ML WATER, 2000 ML ALCOHOL, IN LESS THAN 1000 ML METHANOL, IN MORE THAN 10 ML ETHYL ACETATE|In water, 1.5X10+5 mg/L at 25 °C (est)

2-8°C

LD50 in mice, rats (mg/kg): 2.14, 1.74 i.v. (Slavik, Carter)

D20 -51° (c = 0.4 in ethanol)

ODORLESS

pKa1 = 6.9; pKa2 = 7.7 (naphthalene hydroxyls) (est)

log Kow = 2.4 (est)|Hydroxyl radical reaction rate constant = 5.0X10-10 cu cm/molecule-sec at 25 °C (est)

III

6.1(b)

3249

3

22-26/27/28

45-38-36/37/39-28A-22

PZ2800000

Xn,T+

HYGROSCOPIC, DECOMP SLOWLY IN LIGHT, & DECOMP IN HEAT

H302

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 MITHRAMYCIN (8 total), please visit the HSDB record page.

|Warning|H302 (95.45%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 44 companies from 4 notifications to the ECHA C&L Inventory.

/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 MITHRAMYCIN (19 total), please visit the HSDB record page.

The most important form of toxicity associated with the use of plicamycin consists of a dose-related bleeding syndrome which usually begins with an episode of epistaxis. Plicamycin crosses the blood-brain barrier; the concentration found in brain tissue is low but it persists longer than in other tissues.

Chemotherapy with plicamycin causes serum enzyme elevations in almost all patients who are treated for more than 1 or 2 days and who are monitored during therapy. Serum ALT, AST and LDH values begin to rise within 3 days of the first infusion and peak within 7 to 10 days at levels of 5 to 500 times the upper limit of the normal range (ULN). The elevations, however, are transient and resolve within 1 to 3 weeks and are rarely associated with symptoms or jaundice. Liver biopsies taken during these episodes usually demonstrate centrolobular necrosis and congestion. With repeated courses, elevations continue to occur generally to the same or lesser degree. A single instance of acute liver failure arising within days of therapy that was suggestive of ischemic hepatitis or sinusoidal obstruction syndrome has been reported in a patient treated with full doses of plicamycin for 4 days for nonmalignant hypercalcemia. Otherwise, the serum enzyme elevations, despite being moderate to severe, are transient and benign.

Plicamycin-induced hypoprothrombinemia may increase the activity of coumarin- and indandione-derivative anticoagulants and may increase the risk of bleeding in patient receiving heparin or thrombolytic agents; concurrent use is not recommended.|Concurrent use /of nonsteroidal anti-inflammatory drugs, aspirin, dextran, dipyridamole, sulfinpyrazone, or valproic acid/ with plicamycin may increase the risk of hemorrhage because of additive or multiple actions, which may decrease the blood-clotting ability, ie, inhibition of platelet aggregation, by these medications and/or plicamycin combined with induction of hypoprothrombinemia by plicamycin and large dose of aspirin; in addition, the gastrointestinal ulcerative or hemorrhagic potential of aspirin, the nonsteroidal anti-inflammatory drugs, or sulfinpyrazone may increase the risk of hemorrhage in plicamycin-treated patients.|Concurrent use /of other bone marrow depressants, hepatotoxic medications, or nephrotoxic medications/ may increase the potential for toxicity.|Concurrent use /of vitamin D, including calcifediol and calcitriol/ may antagonize the effect of plicamycin when used as a calcium antagonist.

LD50 Rat iv 1.74 mg/kg|LD50 Mouse iv 2.14 mg/kg

There is no evidence of protein binding, nor is there any evidence of metabolism of the carbohydrate moiety of the drug to carbon dioxide and water with loss through respiration.

/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 the treatment of testicular cancer, as well as hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer.

Plicamycin, which was formerly known as mithramycin, is an antibiotic that is used as an anticancer agent in the therapy of testicular and germ cell cancers. Plicamycin causes acute hepatic injury that arises within days of starting therapy, but is usually transient and asymptomatic and rarely leads to jaundice. Plicamycin has not been approved for use as cancer chemotherapy in the United States, but continues to be used on an investigational basis.

Antineoplastic Agents

Mesh Heading: Antibiotics, antineoplastic, fluorescent dyes, nucleic acid synthesis inhibitors, protein synthesis inhibitors|Plicamycin is of limited value in the treatment of neoplastic disease because of its severe toxicity.|Because of low incidence of testicular tumors (est. to be 1% of all tumors), number of cases evaluated is limited.|It has been beneficial in patients with disseminated testicular carcinomas, especially of the embryonal-cell type, but has been largely superseded by other drug regimens, particularly vinblastine, cisplatin, and bleomycin.|For more Therapeutic Uses (Complete) data for MITHRAMYCIN (12 total), please visit the HSDB record page.

It is recommended that plicamycin be administered by intravenous infusion only to hospitalized patients by or under the supervision of a physician experienced in the use of cancer chemotherapeutic agents because of the possibility of severe reactions.|Hemorrhagic syndrome occurs in about 5% of patients who receive no more than 30 ug/kg/day for no more than 10 doses, whereas it is about 12% for higher doses.|BASELINE PLATELET COUNTS, PROTHROMBIN TIME, & BLEEDING TIME SHOULD BE DETERMINED BEFORE THERAPY IS BEGUN. THESE SHOULD BE MONITORED DURING THERAPY & FOR SEVERAL DAYS FOLLOWING LAST DOSE. SIGNIFICANT DECR IN PLATELET COUNT...OR SIGNIFICANT PROLONGATION OF PROTHROMBIN OR BLEEDING TIMES ARE INDICATIONS FOR DISCONTINUING DRUG.|METASTATIC LESIONS IN PATIENTS WITH MIXED PRIMARY TUMORS OF TESTES HAVE BEEN ONLY PARTIALLY REDUCED OR WERE UNAFFECTED... USUALLY, THESE...IDENTIFIED AS TERATOMAS, CHORIOCARCINOMAS, OR SEMINOMAS. USE...IS NOT RECOMMENDED FOR TREATMENT OF METASTASES DUE TO THESE CELL TYPES.|For more Drug Warnings (Complete) data for MITHRAMYCIN (17 total), please visit the HSDB record page.

Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally.

Hormones and molecules with calcium-regulating hormone-like actions that modulate OSTEOLYSIS and other extra-skeletal activities to maintain calcium homeostasis. (See all compounds classified as Calcium-Regulating Hormones and Agents.)|Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. (See all compounds classified as Fluorescent Dyes.)|Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)|Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)|Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. (See all compounds classified as Protein Synthesis Inhibitors.)

Radioautography studies with 3H-labeled plicamycin in mice show that the greatest concentrations of the isotope are in the Kupffer cells of the liver and cells of the renal tubules. Plicamycin is rapidly cleared from the blood within the first 2 hours and excretion is also rapid. 67% percent of measured excretion occurs within 4 hours, 75% within 8 hours, and 90% is recovered in the first 24 hours after injection.|It is not known whether plicamycin is excreted in breast milk.|Duration of action: 7 to 10 days with a single dose.|Time to peak effect: 72 hours with a single dose.|Onset of action: When used for hypercalcemia, a reduction in plasma calcium usually occurs within 24 to 48 hours following administration.|Plicamycin is concentrated in the Kupffer cells of the liver, in renal tubular cells, and along formed bone surfaces. It may localize in areas of active bone resorption. Plicamycin also crosses the blood-brain barrier and enters the cerebrospinal fluid (CSF).

Plicamycin is presumed to inhibit cellular and enzymic RNA synthesis by forming a complex with DNA. Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D.|The exact mechanism of action is unknown. However, it has been shown that plicamycin forms a complex with DNA in the presence of magnesium or other divalent cations, thereby inhibiting DNA-dependent or DNA-directed RNA synthesis.|Plicamycin is believed to lower serum calcium concentrations, but the exact mechanism is unknown. It may act by blocking hypercalcemic action of vitamin D or by inhibiting the effect of parathyroid hormone on osteoclasts. Plicamycin's inhibition of DNA-dependent RNA synthesis appears to render osteoclasts unable to fully respond to parathyroid hormone with the biosynthesis necessary for osteolysis.|The aureolic acid antitumor antibiotic mithramycin (MTM) inhibits both cancer growth and bone resorption by cross-linking GC-rich DNA, thus blocking binding of Sp-family transcription factors to gene regulatory elements. Transcription of c-src, a gene implicated in many human cancers and required for osteoclast-dependent bone resorption, is regulated by the binding of Sp factors to specific elements in its promoter. Therefore, this gene represents an important anticancer target and a potential lead target through which MTM displays its so far uncharacterized action against osteoclastic bone resorption. Here we demonstrate, using DNA binding studies, promoter reporter assays, and RT-PCR, that MTM inhibits Sp binding to the c-src promoter region, thereby decreasing its expression in human cancer cells. Furthermore, selected mithramycin analogues, namely, premithramycin B, mithramycin SK, 7-demethylmithramycin, 4E-ketomithramycin, and 4C-ketodemycarosylmithramycin, generated through combinatorial biosynthesis, were compared with MTM for their ability to block Sp binding to the c-src promoter. Although most of the tested compounds lost their ability to bind to the DNA, alteration of the MTM 3-pentyl side chain led to a compound (mithramycin SK) with the same DNA binding specificity but with lower binding affinity than MTM. While this compound was comparable to MTM in promoter reporter, gene expression, and anticancer assays, given its weaker interaction with the DNA, it may be much less toxic than MTM. The results presented here supplement recent findings and, moreover, allow new conclusions to be made regarding both the structure-activity relationships, particularly with respect to the alkyl side chains, and the mechanism of action of aureolic acid drugs.|Mithramycin is an mRNA synthesis inhibitor that has been used to decrease bone resorption in patients with humoral hypercalcemia and Paget's disease. During studies on the mechanism of action of mithramycin it became clear that the compound has a direct inhibitory effect on osteoclastic bone resorption in the in vitro bone slice assay. At concentrations of 0.1 - 100 nM mithramycin directly inhibited osteoclastic bone resorption dose-dependently up to 66 + or - 5% at 100 nM (mean + or - SEM, 3 expts.). Another mRNA synthesis inhibitor, actinomycin D (0.1 - 100 nM) and the protein synthesis inhibitor, cycloheximide (0.1 - 10 M), also dose-dependently inhibited osteoclastic bone resorption by 78 + or - 7% at 100 nM and 76 + or - 7% at 10 M, respectively. Mithramycin and actinomycin D at 100 nM did not affect osteoclast survival on bone slices and were therefore not cytotoxic at the concentrations used. Mithramycin (100 nM) and cycloheximide (10 M) both slightly decreased osteoctast cytoplasmic spreading. Addition of 100 nM mithramycin 6 hr after osteoclast adhesion to bone slices still inhibited subsequent resorption by 50%, indicating a continued but lesser requirement for mRNA synthesis during bone resorption. These results show that 75% of osteoclasts obtained from neonatal rat long bones are activated by adhesion to mineralized bone surfaces and require mRNA and protein synthesis in order to resorb bone in vitro.|For more Mechanism of Action (Complete) data for MITHRAMYCIN (6 total), please visit the HSDB record page.

/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/ STRIKING CUTANEOUS EFFECT...WHEN DRUG IS GIVEN DAILY UNTIL TOXIC REACTIONS OCCUR. ...OBSERVED DAY BEFORE ONSET OF BIOCHEMICAL CHANGES & IS CHARACTERIZED INITIALLY BY ERYTHEMA OF FACE, NECK, & UPPER THORAX WITH PERIORBITAL PALLOR. ...HYPEREMIA WITH...THICKENING OF FACIAL FOLDS & PAPULAR LESIONS. ...RESIDUAL PIGMENTATION...|/SIGNS AND SYMPTOMS/ MOST COMMON UNTOWARD EFFECTS ARE NAUSEA, VOMITING, DIARRHEA, ANOREXIA, & STOMATITIS. LESS FREQUENTLY THERE OCCUR FEVER, FACIAL FLUSHING, RASH, PHLEBITIS, MALAISE, HEADACHE, DROWSINESS, ASTHENIA, LETHARGY, DEPRESSION, HEPATIC DYSFUNCTION, RENAL INSUFFICIENCY, HYPOCALCIURIA, HYPOPOTASSEMIA, HYPOPHOSPHATEMIA, & LEUKOPENIA.|/SIGNS AND SYMPTOMS/ Toxic effects of plicamycin on oral and GI mucosa include anorexia, nausea, vomiting, diarrhea, and stomatitis. The incidence and severity of these reactions increase when the drug is administered by rapid, direct IV injection. Antiemetic drugs given prior to and during plicamycin therapy may be helpful in relieving nausea and vomiting.|/SIGNS AND SYMPTOMS/ STUDIES DEMONSTRATED DRUG DEPENDENT, REVERSIBLE HEMORRHAGIC DIATHESIS ASSOC WITH PROLONGATION OF BLEEDING TIME, DECR PLATELET AGGREGATION RESPONSES TO ADP, COLLAGEN, & EPINEPHRINE, DEPLETED PLATELET STORES OF ADP IN ABSENCE OF THROMBOCYTOPENIA & ONSET OF MUCOCUTANEOUS BLEEDING IN PATIENTS.|For more Human Toxicity Excerpts (Complete) data for MITHRAMYCIN (10 total), please visit the HSDB record page.

Aureolic Acid

Plicamycin (mithramycin; mithracin), is available as a powder in vials containing 2.5 mg of drug.

GLC MASS SPECTROMETRY OF SEVERAL IMPORTANT ANTICANCER DRUGS.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients