Vindesine

753.93

753.93

258-682-2

DTXSID6023739

Crystal from ethanol-methanol

L01CA03|L - Antineoplastic and immunomodulating agents

164.82000

2.94

1.4±0.1 g/cm3

230-232 °C

1.708

7.00e-02 g/L

Intact vials should be refrigerated at 2-8 deg C. The constituted soln is stable under refrigeration for 30 days. /Vindesine sulfate/

D25 +39.4° (c = 1.0 in methanol)

pKa: 6.04, 7.67

II

6.1(a)

1544

Vindesine sulfate is most stable at pH 1.9. It may precipitate in a soln with a pH >6. Vindesine sulfate 20 ug/ml in dextrose 5% in water, Ringer's injection, lactate, or sodium chloride 0.9% underwent no degradation after 4 wk when frozen at -20 deg C. /Vindesine sulfate/

P201, P202, P264, P270, P280, P281, P301+P310, P305+P351+P338, P308+P313, P310, P321, P330, P405, P501

H300

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.

Leukopenic and/or thrombocytopenic effects of vindesine may be increased with concurrent or recent therapy if these medications /blood dyscrasia causing medications/ cause the same effects; dosage adjustment of vindesine, if necessary, should be based on blood counts.|Additive bone marrow depression, including severe dermatitis and/or mucositis, may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively.|Acute shortness of breath and severe bronchospasm have frequently been reported with combination therapy including vinca alkaloids; the reaction may occur within minutes or several hours after the vinca alkaloid is injected.|Neurologic toxicity may occur early in treatment and may be more severe if used concomitantly with other drugs having a neurotoxic potential.|For more Interactions (Complete) data for VINDESINE (7 total), please visit the HSDB record page.

Vindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine. /Included in US product labeling/|Vindesine is indicated for the treatment of non-oat cell lung cancer. /Included in US product labeling/

Benefit-to-risk ratio must be considered before using vindesine in pregnant women. It usually is recommended that use of antineoplastics, especially combination chemotherapy, be avoided during pregnancy whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered. Other hazards to the fetus include adverse reactions seen in adults.|Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of vindesine in children.|It is important to strictly adhere to the recommended dosage schedule. The use of small amounts of vindesine daily for long periods for the treatment of children with acute lymphocytic leukemia is not advised, even though the resulting weekly dosage may be similar to the recommended dosage. Little or no therapeutic benefit has been demonstrated when such regimens are used, and the incidence of adverse reactions is increased|The bone marrow depressant effects of vindesine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

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.)

Vindesine causes the arrest of cells in metaphase mitosis. It is three times more potent than vincristine and nearly 10 times more potent than vinblastine in causing mitotic arrest in in vitro studies at doses designed to arrest from 10 to 15% of the cells in mitosis.Vindesine and vincristine are approximately equipotent at dose levels that arrest 40 to 50% of the cells in mitosis. Unlike vinblastine, vindesine produces very few postmetaphase cells.Vindesine has demonstrated activity in patients who have relapsed while receiving multiple-agent treatment that included vincristine. Toxic doses of vindesine given to male and female rats have not affected fertility.

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison 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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

Overdose (45 mg instead of 4.5 mg) leads to generalized muscle pain, tinnitus, diarrhea, sleeplessness, burning sensation in mouth, & hiccups. Patients usually respond to supportive treatment (parenteral nutritional leucovortin, citruline 600 mg/day, arginine 1200 mg/day, & ornithine 600 mg/day).|Neurotoxicity forms a major limitation in many clinical applications of vincristine and other powerful vinca alkaloid anticancer drugs. Using the nerve growth factor (NGF) dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the effect of different concentrations of vincristine (0.55; 1.1 and 11 nM) was compared with that of vindesine and vinblastine. Vincristine in comparatively low concentration (0.55 nM) could significantly decrease the percentage of neurite forming cells from 74% to 32% within a three day incubation period. Especially the longer neurites (> 2 x cell body) proved to be extremely sensitive for vincristine effects. Vinblastine and vindesine were also able to decrease, dose dependently and significantly, the percentage of neurite forming cells. However, the effects observed were less severe than that of vincristine. The sequentially increasing level of neurotoxicity due to vinblastine, vindesine and vincristine, as observed in the neurite outgrowth inhibition correlates well with previous findings from animal models and with data from the clinical practice. Withdrawal of vincristine resulted in a rapid restoration of neurite formation, suggesting the potential reversibility of neurotoxic effects in these cells. These results provide a validation of the PC12 neurite outgrowth assay as a suitable and reliable model for predicting neurotoxicity.|... Oncoprotein 18 (op18) was first isolated as a molecule overexpressed in several malignant cells, suggesting a function of op18 in malignant processes, such as differentiation in hematologic malignancies, op18 also was found to enhance microtubule deassembly in the cells. Antimitotic agents that bind to tubulin have been used for chemotherapy to treat solid tumors, such as lung carcinoma. Vinca alkaloids, such as vindesine and vincristine, have commonly been used for chemotherapy of nonsmall cell lung carcinoma. The authors examined the role of op18 in the sensitivity of human lung carcinoma cells to antimitotic agents. ... Expression of op18 mRNA was detected in all 17 lung carcinoma cell lines tested by Northern blotting. Oncoprotein 18 cDNA was transfected to SBC-3 human lung carcinoma cells, and the stable transfectants, SBC-3/op1-3, were isolated. The sensitivity of these transfectants against antimitotic agents were examined by the MTT assay in vitro. Cell cycle distribution of the transfectants on DNA histogram was analyzed by flow cytometry. ... Oncoprotein 18-transfected cells showed higher sensitivity to vindesine and vincristine, but not to taxanes. Vindesine-exposure increased the G2/M population of the cell cycle in the Mock transfectants, but not in SBC-3/op1, suggesting that the cell cycle dynamics were altered by op18 expression in SBC-3/op1. ... Oncoprotein 18 expression is associated with lung carcinoma cell sensitivity to vindesine and may be able to serve as a surrogate marker for the chemosensitivity to Vinca alkaloids in human lung carcinomas.

Compound 112531