Adverse interactions between antifungal azoles and vincristine: Review and analysis of cases

Brad Moriyama, Stacey A. Henning, Janice Leung, Oluwaseun Falade-Nwulia, Paul Jarosinski, Scott R. Penzak, Thomas J. Walsh

Research output: Contribution to journalReview article

92 Scopus citations

Abstract

Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8years (1.3-68years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5days with itraconazole, 13.5days posaconazole and 30days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life-threatening drug interaction.

Original languageEnglish
Pages (from-to)290-297
Number of pages8
JournalMycoses
Volume55
Issue number4
DOIs
StatePublished - Jul 2012

Keywords

  • Azole antifungal
  • Drug interactions
  • Vincristine

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    Moriyama, B., Henning, S. A., Leung, J., Falade-Nwulia, O., Jarosinski, P., Penzak, S. R., & Walsh, T. J. (2012). Adverse interactions between antifungal azoles and vincristine: Review and analysis of cases. Mycoses, 55(4), 290-297. https://doi.org/10.1111/j.1439-0507.2011.02158.x