Risk of azole-enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: old problem - new dilemma

Pediatr Blood Cancer. 2011 Jul 15;57(1):30-5. doi: 10.1002/pbc.22972. Epub 2011 Jan 24.

Abstract

One of the most well-known drug interactions in pediatric oncology concerns the co-administration of itraconazole, an antifungal triazole, and vincristine, an antileukemic agent, which seems to enhance the risk of neurotoxicity of the latter, mediated through the cytochrome CYP450 enzyme system. The aim of this article is to review the metabolism of these two drugs, to analyze the published cases with severe triazole-enhanced vincristine neurotoxicity, to discuss the pathophysiological mechanisms of this adverse effect, and to contribute in understanding the differences in triazole-vincristine interaction severity.

Publication types

  • Review

MeSH terms

  • Antifungal Agents* / pharmacokinetics
  • Antifungal Agents* / therapeutic use
  • Antifungal Agents* / urine
  • Antineoplastic Agents, Phytogenic* / adverse effects
  • Antineoplastic Agents, Phytogenic* / pharmacokinetics
  • Antineoplastic Agents, Phytogenic* / therapeutic use
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Itraconazole* / adverse effects
  • Itraconazole* / pharmacokinetics
  • Itraconazole* / therapeutic use
  • Risk Factors
  • Vincristine* / adverse effects
  • Vincristine* / pharmacokinetics
  • Vincristine* / therapeutic use

Substances

  • Antifungal Agents
  • Antineoplastic Agents, Phytogenic
  • Itraconazole
  • Vincristine
  • Cytochrome P-450 Enzyme System