(+)-Vincristine

824.96

824.96

200-318-1

1544

DTXSID1032278

Blades from methanol

L01CA02|L - Antineoplastic and immunomodulating agents

171

2.8

Vincristine appears as a white crystalline solid. Melting point 218°C. Used as an antineoplastic.

1.4±0.1 g/cm3

218-220 °C

1.677

3.00e-02 g/L

LD50 i.p. in mice: 5.2 mg/kg (Adamson)

D25 +17°; D25 +26.2° (ethylene chloride)

pKa: 5.0, 7.4 in 33% dimethylformamide

Crystals from ethanol. MP: 273-281 °C. One part soluble in 2 parts water, in 30 parts chloroform. Slightly soluble in ethanol. Practically insoluble in ether. Specific optical rotation: +8.5 deg at 26 °C/D ( c = 0.8). UV max (methanol): 218,252, 285, 293 nm (log epsilon 4.72, 4.24, 4.18, 4.23) /Sulfate/|Slightly soluble in alcohol. /Vincristine sulfate/|Hydroxyl radical reaction rate constant = 6.73X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 4.3X10-18 cu cm/molec-sec at 25 °C (est)

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

Alcohols and Polyols

II

6.1(a)

1544

Stable, but may be heat sensitive. Incompatible with strong oxidizing agents.

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

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl vincristine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /Vincristine sulfate/

Weisburger EK; Bioassay Program for Carcinogenic Hazards of Cancer Chemotherapeutic Agents; Cancer 40: 1935-49 (1977). Route: intraperitoneal injection; Species: rats and mice.|Zhou XJ, Rahmani R; Preclinical and Clinical Pharmacology of Vinca Alkaloids. Drugs 44 (Suppl 4): 1-16; 66-9 (1992). Vinca alkaloids, including vinblastine, vincristine, vindesine and vinorelbine, are widely used antineoplastic drugs, either as single agents or in combination with other drugs. Numerous studies have been conducted in animals and humans, using various in vivo and in vitro models, to investigate the pharmacological behavior of this class of antitumor drug.

Flash point data for this chemical are not available, but it is probably combustible. (NTP, 1992)

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

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

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

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

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

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

Concurrent administration of vincristine sulfate with itraconazole (a known inhibitor of the metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects (see Adverse Reactions). This interaction is presumed to be related to inhibition of the metabolism of vincristine.|The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination.|The effects of bovine brain gangliosides on the neurotoxicity of vincristine were investigated in dissociated cultures of dorsal root ganglion cells from 10 day chick embryos. The effects of the drugs were quantified as the numbers of neurite bearing cells or total neurite length in individual neurite bearing cells. The administration of vincristine (1 to 1000 pg/mL) inhibited neurite outgrowth from the cells, whereas gangliosides (10 to 1000 ug/mL) protected them against this inhibition in a concentration dependent manner. Electron microscopy revealed vincristine induced fragmentation and longitudinal disorientation of microtubules in neurites and showed the protection by gangliosides against such damaging effects. Results show that exogenous administration of gangliosides attenuates the neurotoxicity of vincristine in vitro.|Verapamil has been shown to overcome acquired drug resistance to vincristine in P388 leukemia both in vitro and in vivo. To study the selectivity of this action, the effect of addition of verapamil on the cytotoxicity of vincristine was studied using lymphocytes from eight patients with chronic lymphocytic leukemia, lymphoblasts from a T-acute lymphoblastic leukemia cell line (GM 3639), and peripheral blood lymphocytes from eight normal healthy volunteers. Using the differential staining cytotoxicity assay, it was demonstrated that verapamil at 1 uM concentration potentiated the in vitro cytotoxicity of vincristine on chronic lymphocytic leukemia and GM 3639 cells in concentrations of 0.04-0.25 ug/L. There was however, no enhancement of cytotoxicity noted against the control peripheral blood lymphocytes. The data demonstrate that verapamil preferentially enhances the in vitro cytotoxicity of vincristine on chronic lymphocytic leukemia and GM 3639 cells but no enhancement of cytotoxicity is seen against peripheral blood lymphocytes.|For more Interactions (Complete) data for VINCRISTINE (6 total), please visit the HSDB record page.

Patients with the demyelinating form of Charcot-Marie-Tooth syndrome should not be given vincristine sulfate injection.|Because of the hepatic metabolism and biliary excretion of vincristine, some clinicians recommend reduced doses in patients with obstructive jaundice or other hepatic impairment. Vincristine must be given with care, and dosage and toxicity monitored, in patients receiving other neurotoxic drugs or those with preexisting neuromuscular disease.

An alkaloid isolated from Vinca rosea.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,072 workers (933 of these were female) were potentially exposed to vincristine in the US(1). Occupational exposure to vincristine may occur through inhalation and dermal contact with this compound at workplaces where vincristine is produced or used. Exposure to vincristine among the general population may be limited to those administered this drug, an antineoplastic(SRC).

Antineoplastic Agents, Phytogenic|Vincristine sulfate injection is indicated in acute leukemia. /Included in US product label/|Vincristine sulfate injection has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non-Hodgkin's malignant lymphomas (lymphocytic, mixed cell, histiocytic, undifferentiated, nodular and diffuse types), rhabdomyosarcoma, neuroblastoma, and Wilms' tumor. /Included in US product label/|Vincristine is used as a component of various chemotherapeutic regimens for the treatment of disseminated Hodgkin's disease. Combination therapy for Hodgkin's disease is clearly superior to single drug therapy. Various drugs have been used for combination chemotherapy, and comparative efficacy of these regimens is continually being evaluated. Vincristine is most frequently used in combination with mechlorethamine, procarbazine, and prednisone or prednisolone (known as the MOPP regimen), given intensively for at least 6 cycles.|For more Therapeutic Uses (Complete) data for VINCRISTINE (9 total), please visit the HSDB record page.

/BOXED WARNING/ WARNINGS: Caution-This preparation should be administered by individuals experienced in the administration of Vincristine Sulfate Injection, USP. It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection, USP may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis. FOR INTRAVENOUS USE ONLY - FATAL IF GIVEN BY OTHER ROUTES.|Because of the hepatic metabolism and biliary excretion of vincristine, some clinicians recommend reduced doses in patients with obstructive jaundice or other hepatic impairment. Vincristine must be given with care, and dosage and toxicity monitored, in patients receiving other neurotoxic drugs or those with preexisting neuromuscular disease. ... Vincristine should not be administered to patients while they are receiving radiation therapy through ports that include the liver.|Vincristine can cause fetal toxicity when administered to pregnant women. ... There are no adequate and controlled studies to date using vincristine in pregnant women, and the drug should be used during pregnancy only in life threatening situations or severe disease for which safer drugs cannot be used or are ineffective. Women of childbearing potential should be advised to avoid becoming pregnant while receiving the drug. When vincristine is administered during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.|Vincristine is a tissue irritant and may cause phlebitis and necrosis. Extravasation results in pain and cellulitis. ... Local injection of hyaluronidase and application of moderate heat may decrease local reactions resulting from extravasation; however, some clinicians prefer to treat extravasation with cold compresses, dilution with 0.9% sodium chloride injection or infiltration of sodium bicarbonate (5 mL of 8.4% injection), and/or local injection of hydrocortisone.|For more Drug Warnings (Complete) data for VINCRISTINE (23 total), please visit the HSDB record page.

Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES. (See all compounds classified as Tubulin Modulators.)|Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. (See all compounds classified as Antineoplastic Agents, Phytogenic.)

Development of CNS leukemia in patients receiving vincristine and in hematological remission has been interpreted as evidence that ... /vincristine/ penetrates blood-brain barrier poorly. Vincristine ... can be infused into arterial blood supply of tumors in doses several times larger than those that can be admistered iv with comparable toxicity; thus either local uptake or destruction is very rapid. Vinca alkaloids appear to be excreted primarily by liver into bile.|Urinary excretion ... over first few hr after injection was ... low in dogs and monkeys. In both ... the drug was distributed to most tissues, but highest concentrations ... found in lung, kidney, spleen, pancreas and liver. In monkeys, vincristine and its metabolites rapidly entered cerebrospinal fluid from plasma to form low concentrations of drug, which persisted for several days.|Vincristine sulfate is unpredictably absorbed from the Gl tract. Following rapid iv injection of a 2 mg dose of vincristine in patients with normal renal and hepatic function, peak serum drug concentrations of approximately 0.19-0.89 uM occur immediately and the drug is rapidly cleared from serum. The area under the serum vincristine concentration time curve has been shown to be increased following continuous iv infusion compared with rapid iv injection of the drug when comparable doses are administered.|Distribution of vincristine and its metabolites (and/or decomposition products) into human body tissues and fluids has not been fully characterized, but the drug is rapidly and apparently widely distributed following iv administration. Drug that is distributed into tissues is tightly but reversibly bound. Vincristine and its metabolites (and/or decomposition products) are rapidly and extensively distributed into bile, with peak biliary concentrations occurring within 2-4 hr after rapid iv injection of the drug. Vincristine and its metabolites (and/or decomposition products) cross the blood brain barrier poorly following rapid iv injection and generally do not appear in the CSF in cytotoxic concentrations.|For more Absorption, Distribution and Excretion (Complete) data for VINCRISTINE (6 total), please visit the HSDB record page.

After iv administration of ... (3)H vincristine, 69% of radioactivity was recovered in feces and 12% in urine over 72 hr period. Approx half ... was in form of metabolites, whose UV spectrum suggested that vincristine dimer was intact. Patients with biliary fistula showed extensive biliary excretion of intact drug (46.5%) & of metabolites (53.5%). Observations suggest that biliary-fecal route ... predominate in excretion ... .|The metabolic fate of vincristine has not been clearly determined; the drug appears to be extensively metabolized, probably in the liver, but the extent of metabolism is not clear since the drug also apparently undergoes decomposition in vivo.

After iv administration of ... (3)H vincristine, triphasic decay was observed, with half-lives of 0.85, 7.4 and 164 min ...|Following rapid iv injection of vincristine, serum concentrations of the drug appear to decline in a triphasic manner. The terminal elimination half-life of vincristine has ranged from 19-155 hr.

Vinca alkaloids are cell cycle specific agents ... /which/ block mitosis and produce metaphase arrest. Biological activities of these drugs can be explained by their ability to bind specifically tubulin, and to block ability of the protein to polymerize into microtubules ... through disruption of microtubules of mitotic apparatus, cell division is arrested in metaphase. In absence of intact mitotic spindle, chromosomes may disperse throughout cytoplasm ... or may occur in unusual groupings ... inability to segregate chromosomes correctly during mitosis presumably leads to cellular death. /Vinca alkaloids/|Although the mechanism of action has not been definitely established, vincristine appears to bind to or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerization and causing metaphase arrest. In high concentrations, the drug also exerts complex effects on nucleic acid and protein synthesis. Vincristine exerts some immunosuppressive activity.

3'-hydroxyvincristine; 4'-deoxyvincristine; N-desmethylvinblastine; deacetylvincristine; deacetylvinblastine; vinblastine; leurosine; formylleurosine

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. (ERG, 2016)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. Strychnine is an exceptionally toxic poison but inducing vomiting may cause a seizure. IMMEDIATELY call a hospital or poison control center and locate activated charcoal, egg whites, or milk in case the medical advisor recommends administering one of them. If advice from a physician is not readily available and the victim is conscious and not convulsing, give the victim a glass of activated charcoal slurry in water or, if this is not available, a glass of milk, or beaten egg whites and IMMEDIATELY transport victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, assure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Extravasation: Immediately stop the infusion and withdraw as much fluid as possible by negative pressure on the syringe. Then give the following specific treatment: Place a heating pad over the area and apply heat intermittently for 24 hours; elevate the limb. Local injection of hyaluronidase may be beneficial. Do not use ice packs. /For/ decontamination administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Because of the rapid intracellular incorporation of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/|Following vincristine overdosage, supportive and symptomatic treatment should be initiated. Treatment should include the prevention of adverse effects resulting from the syndrome of inappropriate secretion of antidiuretic hormone (eg, by restricting fluid intake and possibly by use of an appropriate diuretic); prophylactic administration of phenobarbital in anticonvulsant doses; use of enemas to prevent ileus (in some cases, decompression of the GI tract may be necessary); monitoring of the cardiovascular system; and daily blood counts to monitor the hematologic system and guide transfusion requirements. Studies in mice and a few case reports have suggested that administration of leucovorin calcium may be of some value in the management of vincristine overdosage. ... Treatment with leucovorin calcium does not preclude the need for the usual treatment measures.|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/|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/|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/

/HUMAN EXPOSURE STUDIES/ Fifteen children suffering from leukemia were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs) in the absence and presence of contralateral white noise on day 1 and on day 22 of treatment with vincristine. The function of the medial olivocochlear bundle was assessed by the phenomenon of suppression of otoacoustic emissions by contralateral application of white noise. The study revealed a statistically significant decrease of contralateral suppression amplitudes in all cases after three sessions of chemotherapy with vincristine. On the contrary no alterations were observed in pure tone audiometry thresholds. A non-significant decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by frequency, however, this decrease reached the level of statistical significance at two frequencies. Vincristine treatment seems to exert a neurotoxic effect on the efferent olivocochlear system, which takes place early in the course of chemotherapy.|/HUMAN EXPOSURE STUDIES/ Overdosage with vincristine produces adverse effects that are mainly extensions of common adverse effects. Doses 10 times the usual recommended doses have been lethal in children younger than 13 yr of age, and severe manifestations of toxicity have been apparent following administration of 3-4 mg/sq m in this age group. Single doses of 3 mg/sq m can be expected to produce severe toxic manifestations in adults.|/SIGNS AND SYMPTOMS/ Clinical toxicity ... is mostly neurological, with paresthesias, loss of deep-tendon reflexes, neuritic pain, muscle weakness that may be manifested by foot-drop & inability to walk, hoarseness, headache, ptosis, & double vision. Severe constipation, sometimes resulting in colicky abdominal pain and obstruction ... .|/SIGNS AND SYMPTOMS/ Alopecia occurs in about 20% of patients given vincristine ... although less common than with vinblastine, leukopenia may occur with vincristine, & thrombocytopenia, anemia, polyuria, dysuria, fever, and GI symptoms ... reported occasionally. Syndrome of hyponatremia associated with high urinary sodium and inappropriate ADH secretion has been occasionally observed during ... therapy.|For more Human Toxicity Excerpts (Complete) data for VINCRISTINE (26 total), please visit the HSDB record page.

cellcristin

VINCRISTINE SULFATE, SUP (ONCOVIN), IS AVAILABLE AS DRY POWDER IN AMPULS CONTAINING EITHER 1 OR 5 MG OF DRUG. /VINCRISTINE SULFATE/|Parenteral Injection, for iv use only, 1 mg/mL Vincristine Sulfate Injection (preservative-free), Hospira, Teva|Vials and syringes, 1, 2, and 5 mg /Vincristine sulfate/

For the treatment of acute leukemia, malignant lymphoma, Hodgkins disease, acute erythremia, acute panmyelosis

Analyte: vincristine sulfate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /vincristine sulfate/|Analyte: vincristine sulfate; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 297 nm with comparison to standards /vincristine sulfate/|Analyte: vincristine sulfate; matrix: pharmaceutical preparation (injection; injection solution); procedure: thin-layer chromatography with comparison to standards (chemical identification) /vincristine sulfate/|Analyte: vincristine sulfate; matrix: pharmaceutical preparation (injection; injection solution); procedure: liquid chromatography with ultraviolet detection at 297 nm with comparison to standards (chemical purity) /vincristine sulfate/|For more Analytic Laboratory Methods (Complete) data for VINCRISTINE (9 total), please visit the HSDB record page.

RADIOIMMUNOASSAY IS USED TO ANALYZE BIOLOGICAL FLUIDS. LIMIT OF DETECTION IS 450 NG.|TRITIATED VINCRISTINE & ITS METABOLITES OF DEGRADATION PRODUCTS HAVE BEEN SEPARATED BY HPLC ... IN BILE ... .|Analyte: vincristine; matrix: blood (plasma, serum); procedure: high-performance liquid chromatography with ultraviolet detection at 300 nm or electrochemical detection; limit of detection: 1 ng/mL (ultraviolet), 0.3 ng/mL (electrochemical)|Analyte: vincristine; matrix: blood (plasma, whole); procedure: high-performance liquid chromatography with ultraviolet detection at 221 nm; limit of detection: less than 120 ng/mL|For more Clinical Laboratory Methods (Complete) data for VINCRISTINE (7 total), please visit the HSDB record page.