Vincristin

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)

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated contain

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

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.

/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.

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；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 the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank 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, 2024)

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/

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.

Vincristine exhibits various adverse effects that can affect multiple organ systems and vary in severity. Notable organ systems encompassed by vincristine's potential adverse effects include cardiovascular, CNS, dermatological, endocrine and metabolic, gastrointestinal, genitourinary, hepatic, renal, respiratory, neuromuscular, otic, and ophthalmic systems.；Some adverse effects that can occur during vincristine administration, categorized by body system, are outlined below.；Neurotoxicity: This is the most prevalent and dose-limiting adverse effect of vincristine, often manifesting as peripheral neuropathy, which can impact sensory, motor, and autonomic nerves. The symptoms of this condition include numbness, tingling, pain, weakness, difficulty walking or using the hands, loss of reflexes, constipation, urinary retention, orthostatic hypotension, and impotence. Neurotoxicity can also affect the CNS, causing seizures, confusion, hallucinations, depression, cranial nerve palsies, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Neurotoxicity typically exhibits reversibility upon discontinuation or dose reduction of vincristine, although in some instances, it may persist for months or even years.；Myelosuppression: Myelosuppression refers to the inhibition of bone marrow function, leading to a decreased production of blood cells. Vincristine can cause mild-to-moderate myelosuppression, mainly affecting platelets and white blood cells. The symptoms include bleeding, bruising, infection, fever, and anemia. Although myelosuppression is generally reversible following discontinuation or dose reduction of vincristine, in some cases, it may necessitate supportive measures such as blood transfusions or growth factor administration.；Alopecia: Alopecia is characterized by hair loss from the scalp and other body areas. This condition can occur as an adverse effect of vincristine and result in partial or complete hair loss in a majority of patients. Typically, hair regrowth occurs after the discontinuation or completion of vincristine therapy, although it may exhibit a different color or texture.；Gastrointestinal toxicity: This condition includes symptoms such as nausea, vomiting, diarrhea, abdominal pain, mucositis characterized by inflammation of the mouth and throat, and anorexia characterized by loss of appetite. These effects are usually of mild-to-moderate severity and can often be effectively managed by the use of antidiarrheals, antiemetics, which are medications to prevent nausea and vomiting, analgesics, which are pain relievers, and nutritional support.；Other adverse effects: Vincristine can also cause other less common or rare adverse effects, such as hypersensitivity reactions (allergic reactions), extravasation (leakage of the drug into the surrounding tissues), phlebitis (inflammation of the veins), skin rash, photosensitivity (increased sensitivity to sunlight), headache, dizziness, tinnitus (ringing in the ears), blurred vision, hypertension (high blood pressure), arrhythmias (irregular heartbeats), cardiomyopathy (heart muscle damage), pulmonary edema (fluid accumulation in the lungs), hepatotoxicity (liver damage), nephrotoxicity (kidney damage), pancreatitis (inflammation of the pancreas), hyperuricemia (high levels of uric acid in the blood), gout (a type of arthritis caused by uric acid crystals in the joints), and secondary malignancies (new cancers caused by chemotherapy).；Drug-Drug Interactions；Vincristine can interact with numerous other drugs metabolized by the liver enzyme CYP3A4 or transported by the protein P-glycoprotein (P-gp). Such interactions can either elevate or diminish the blood concentrations of vincristine, thereby influencing its efficacy and toxicity. Some examples of drugs that can interact with vincristine are mentioned below.；CYP3A4 inhibitors: These drugs inhibit the activity of CYP3A4 and reduce the metabolism of vincristine. This can lead to elevated plasma concentrations, heightening the risk of neurotoxicity and myelosuppression. Some examples of CYP3A4 inhibitors are ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, erythromycin, clarithromycin, telithromycin, diltiazem, verapamil, grapefruit juice, and cimetidine. When these drugs are coadministered with vincristine, it may be necessary to reduce the vincristine dose or extend the interval between doses.；CYP3A4 inducers: These drugs enhance the activity of CYP3A4, leading to increased metabolism of vincristine. Consequently, this can result in lower plasma concentrations and decreased vincristine efficacy. Some examples of CYP3A4 inducers are rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, primidone, St John's wort, and efavirenz. When coadministered with these drugs, it may be necessary to consider increasing the vincristine dose or shortening the interval between doses.；P-gp inhibitors: These drugs inhibit the function of P-gp and diminish the efflux of vincristine from cells. Consequently, this can lead to higher intracellular concentrations, potentially increasing efficacy and toxicity.；P-gp inducers: These drugs stimulate the expression or function of P-gp, leading to increased efflux of vincristine from cells. This can result in lower intracellular concentrations and decreased efficacy of vincristine.

The administration of vincristine should never be considered an emergency, as several fatal cases have occurred due to the inadvertent administration of vincristine via the incorrect route or at a rapid rate. Therefore, nurses or other healthcare providers responsible for administering vincristine should consistently verify the label for the prescribed dose, duration, and route of administration.；Neurotoxicity: The most prevalent and dose-limiting toxicity associated with vincristine is neurotoxicity, which can impact the peripheral, central, and autonomic nervous systems. The signs and symptoms of neurotoxicity include numbness, tingling, pain, weakness, difficulty walking or using the hands, loss of reflexes, constipation, urinary retention, and orthostatic hypotension. Neurotoxicity typically exhibits reversibility upon discontinuation or dose reduction of vincristine, although in some instances, it may persist for months or even years.；Management of Overdose；If severe or progressive neurotoxicity ensues, it is advisable to either reduce the dose of vincristine or discontinue its use. Symptomatic treatment may include analgesics (pain relievers), anticonvulsants (seizure medications), antidepressants, laxatives, anticholinergics (drugs that block the action of acetylcholine), and physical therapy. Certain medicines that have the potential to exacerbate neurotoxicity, such as isoniazid, phenytoin, metronidazole, and erythromycin, should either be avoided or used cautiously.

The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca²⁺-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=57-22-7]

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

/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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

vincristine

DILI Positive

Intravenous

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Mice given 7 mg/kg body wt ... ip showed muscular weakness and hind leg paralysis and died within 8 days. In rats, prominent signs of toxicity after lethal dose were diarrhea, anorexia, locomotor inactivity, diuresis, loss of wt & dyspnea. Death usually occurred 3-7 days after dosing, with survivors improving from day 7.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In 6 wk study in dogs ... iv injections of 0.08, 0.04 or 0.02 mg/kg body wt/wk /were given/. With highest dose, 2/4 animals died with extensive damage to gut, lymphoid hypoplasia & maturation arrest of spermatocytes. Survivors had no drug-induced lesions at necropsy 44 & 97 days after start of treatment ... but nonspecific lesions of nervous system occurred with all dose levels.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Monkeys treated with i.v. doses of 0.08, 0.16 or 0.32 mg/kg bw per week survived treatment, but showed dose-related leucopenia, anaemia and reticulocytosis. One of two monkeys given 0.64 mg/kg bw per week died; both animals had swollen neurons in the ventral horn of the spinal cord and severe damage to the intestinal mucosa.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Sixty-five rats were used as a control group and 31 rats were divided into two groups and given VCR in two different regimens: the fixed-dose group (0.2 mg/kg) and the increasing-dose group (0.1 mg/kg, by an increment of 0.05 mg/kg/week). VCR was given intraperitoneally once weekly for five consecutive weeks. Electrophysiological examinations of the control and both treated groups were performed and included measurements of nerve conduction velocity and action potential (AP) amplitude of sciatic and tail nerves weekly during the period of treatment and 14 weeks after discontinuation of treatment. Histological sections of sciatic nerves were examined after the appearance of early electrophysiological changes, at the end of the 5th, and 19th weeks of the study (14 weeks after discontinuation of treatment). With the progress of the treatment, an increasing number of rats showing signs of neurological deficits were observed. During the first 5 weeks of this study, electrophysiological testing showed a nonsignificant difference in the conduction velocities of sciatic and tail nerves between the control and the treated groups, whereas a significant decrease in the amplitude of the sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) of the tested nerves was recorded. The reduction in the AP amplitude was associated with histological changes characterized by axonal degeneration with relative demyelination. Fourteen weeks after discontinuation of treatment, a significant increment in the SNAP and CMAP amplitudes of both sciatic and tail nerves was noticed. While the CMAP amplitude of the distal segment of the tail showed nonsignificant increment, lesser number of fibers with axonal and/or myelin lesions were found. The clinical, electrophysiological, and histological results suggest that VCR induces peripheral sensorimotor neuropathy of axonal type more prominent in the fixed- than the incr

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.

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).

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/

... in the treatment of acute leukemia in children /Vincristine sulfate USP/

MEDICATION (VET)

MEDICATION

Therapeutic Category: Antineoplastic

Treatment of acute lymphocytic leukemia (ALL), Hodgkin lymphoma, non-Hodgkin lymphomas, Wilms' tumor, neuroblastoma, rhabdomyosarcoma. Liposomal vincristine is indicated for the treatment of relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL).

Vinblastine and vincristine occur in Catharanthus roseus (L). The plant contains only very small amounts of vinblastine and vincristine, and their isolation is correspondingly difficult. First the alkaloids present are separated by extraction into alkaloid tartrate soluble in benzene and alkaloid tartrates insoluble in benzene. Vinblastine and vincristine belong to the first group. They then are separated by chromatography on aluminum oxide deactivated with acetic acid.

Isolation from Vinca rosea Linn (Catharanthus roseus G Don), Apocynaceae.

USING SUITABLE MODIFICATIONS IN CHROMATOGRAPHIC PART OF PROCESS, VINCRISTINE SULFATE ISOLATING ALKALOID FROM EXTRACT BY USUAL PPT & SOLVENT TECHNIQUES & PURIFYING BY CHROMATOGRAPHY ON ALUMINUM OXIDE. CONVERSION TO SULFATE BY /ADDN OF SULFURIC ACID/ ... . /VINCRISTINE SULFATE/

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/