Vindesine

230-232 °C

230-232 °C

230 - 232 °C

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 °C. /Vindesine sulfate/

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.

Activated charcoal binds most toxic agents and can decrease their systemic absorption if administered soon after ingestion. Immediate dilution with milk or water may be of benefit in caustic or irritant chemical ingestions. If the exposure occurred through inhalation, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. in case of acute lung injury, Maintain ventilation and oxygenation and evaluate with frequent arterial blood gas or pulse oximetry monitoring. Following eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. In case of dermal exposure, Remove contaminated clothing and wash exposed area thoroughly with soap and water. Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines. (T36)

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.

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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Vindesine

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

Studies in rats have indicated that vindesine is embryotoxic and possibly teratogenic. In rabbit studies, doses which produced maternal toxicity were embryotoxic but not teratogenic.

The effect of 0.05 mg/kg body weight of vindesine sulfate was studied on the radiation-induced changes in mouse spermatogenesis at 1, 2, 7, 14, 21, 28, 35 and 70 days post-irradiation. Vindesine administration before exposure to 0, 0.5, 1, 2 and 3 Gy gamma-irradiation resulted in an increase in the radiation-induced perturbations of mouse spermatogenesis at various post-exposure time periods studied. A significant reduction in testicular weight was observed in both DDW + irradiated and VDS + irradiated groups at various post-irradiation time periods, depending on the exposure dose. Vindesine pretreatment resulted in an enhanced killing of spermatogonial cells at day 2 post-exposure at all the exposure doses, except 3 Gy when compared to DDW + irradiated controls. Consequently, the tetraploid (4C) population declined significantly by day 14 post-irradiation followed by a severe depletion in round spermatids (1C) by day 21 post-irradiation. The dose-response relationship for 4C and 1C populations was linear-quadratic at days 14 and 21, respectively. A significant elevation was observed in HC population from days 1 to 21 depending on the exposure dose. The germ cell ratios, viz. 4C:2C, 4C:S-phase, 1C:2C and 1C:4C, showed a significant decline in the VDS + irradiated group when compared to the DDW + irradiated group at various time periods, depending on the exposure dose.

Effect of different concentrations (0, 1, 5, 10, 20 and 50 nM) of vindesine sulphate was studied on clonogenicity and micronucleus (MN) formation in V79 (Chinese hamster lung fibroblasts) cells. Exposure of V79 cells to vindesine for 6 h resulted in a concentration dependent decline in cell survival. The frequency of micronuclei (MN) increased in a concentration dependent manner at 16, 22 and 28 h post-exposure. The frequency of MN increased significantly after 5 to 50 nM drug exposure at 16 and 22 h post-treatment, while increasing post-exposure time to 28 h resulted in a significant increase in MN frequency at all exposure doses of vindesine. The statistical evaluation of concurrent concentrations at various time periods showed a non-significant difference in MN frequency among various post-exposure time periods, except 16 h and 28 h for 50 nM, where a significant decline in the MN frequency was observed at 28 h compared to 16 h post-exposure. The cell proliferation indices showed a concentration dependent decline in the frequency of binucleate cells and this decline was linear quadratic. The increasing drug concentration resulted in a concentration dependent decline in cell survival. While the frequency of micronuclei increased the cell survival decreased and the relationship between cell survival and micronucleus induction was linear quadratic.

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/

L01CA03

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Vindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine and non-oat cell lung cancer. 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 <i>in vitro</i> 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.

Vindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.

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.

Hepatic

Hepatic Half Life: 24 hours.

Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.

Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.

MEDICATION

Vindesine is used in chemotherapy to treat many different types of cancer, including leukaemia, lymphoma, melanoma, breast cancer, and lung cancer (L1022).