Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL

Ann Hematol. 1995 Dec;71(6):311-2. doi: 10.1007/BF01697985.


In four of 14 patients with acute lymphoblastic leukemia (ALL) who received induction chemotherapy containing weekly injections of vincristine and simultaneous antifungal prophylaxis with itraconazole, unusually severe and early vincristine-induced neurotoxicity was observed. In these patients (three female, one male) paresthesia and muscle weakness of the upper/lower extremities and paralytic ileus occurred after the first or second vincristine injection. In one patient a laryngeal nerve paresis required mechanical ventilation. The neurotoxic complications were more serious than those seen in a previous series of 460 ALL patients under the identical cytostatic regimen but without itraconazole prophylaxis. The underlying mechanism is unclear. Interaction with the cytochrome P-450 system, reversal of multidrug resistance, and influence of estrogens are to be considered.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Antifungal Agents / adverse effects*
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Drug Interactions
  • Female
  • Humans
  • Itraconazole / adverse effects*
  • Male
  • Muscle Weakness / chemically induced
  • Paresthesia / chemically induced*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Vincristine / adverse effects*


  • Antifungal Agents
  • Antineoplastic Agents, Phytogenic
  • Itraconazole
  • Vincristine