Vinflunine

Table of contents

  • Brand Names
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Genes that may be involved
  • Substrate of
  • Drug Interactions
  • Nutrition/Nutraceutical Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names

Europe

Austria: Javlor; Bulgaria: Javlor; Czech Republic: Javlor; Denmark: Javlor; Estonia: Javlor; Finland: Javlor; France: Javlor; Germany: Javlor; Greece: Javlor; Ireland: Javlor; Latvia: Javlor; Lithuania: Javlor; Luxembourg: Javlor; Malta: Javlor; Netherlands: Javlor; Poland: Javlor; Portugal: Javlor; Romania: Javlor; Slovakia: Javlor; Slovenia: Javlor; Spain: Javlor; Sweden: Javlor; UK: Javlor.

Drug combinations

Chemistry

Vinflunine Ditartrate: C~53~H~66~F~2~N~4~O~2~0. Mw: 1117.10. ((2β,3β,4β,5α,12R,19α)-4-(acetyloxy)-6,7-didehydro-15-[(2R,4R,6S,8S)-4-(1,1-difluoroethyl)-1,3,4,5,6,7,8,9-octahydro-8-(methoxycarbonyl)-2,6-methano-2-Hazecino[4,3-b]indol-8-yl]-3-hydroxy-16-methoxy-1-methyl-aspidospermidine-3-carboxylic acid methyl ester, (2R,3R)-2,3-dihydroxybutanedioate (1:2). CAS-194468-36-5.

Pharmacologic Category

Antineoplastic Agents, Plant Alkaloids and Other Natural Products. Vinca Alkaloid. (ATC-Code: L01CA05).

Mechanism of action

Vinflunine binds to tubulin at or near the vinca binding sites, inhibiting its polymerization into microtubules, which results in treadmilling suppression, disruption of microtubule dynamics, mitotic arrest and apoptosis. In vivo vinflunine displays a significant antitumor activity against a broad spectrum of human xenografts in mice both in terms of survival prolongation and tumor growth inhibition.

Therapeutic use

Indicated in monotherapy for the treatment of adult patients with advanced or metastatic transitional cell carcinoma of the urothelial tract after failure of a prior platinum-containing regimen.

Pregnancy and lactiation implications

On the basis of the results of animal studies and the pharmacological action of the medicinal product, there is a potential risk of embryonic and fetal abnormalities. Should therefore not be used during pregnancy, unless strictly necessary. Men and women with reproductive potential must use an effective method of contraception during the treatment and up to 3 months after the last vinflunine administration. Due to possible very harmful effects on infants, breast-feeding during treatment with vinflunine is contraindicated.

Unlabeled use

Contraindications

Hypersensitivity to the active substance or other vinca alkaloids. Recent (within 2 weeks) or current severe infection. Baseline neutrophils <1500/mm^3^ or platelets <100000/mm^3^. Lactation.

Warnings and precautions

Neutropenia is a frequent adverse reaction of vinflunine (adequate monitoring of complete blood counts should be conducted). Severe constipation occurred in 15.3% of treated patients. Few QT interval prolongations have been observed after administration of vinflunine (should be used with caution in patients with increased proarrhythmic risk; e.g. congestive heart failure, known history of QT interval prolongation, hypokalemia). Concomitant use of two or more QT/QTc interval-prolonging substances is not recommended. Discontinuation of vinflunine should be considered in patients who develop cardiac ischemia. When infused through a peripheral vein, vinflunine can induce grade 1 to 3 venous irritation.

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