Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies

Acta Paediatr. 2001 Oct;90(10):1204-7. doi: 10.1080/080352501317061675.

Abstract

Eight consecutive paediatric patients with acute lymphoblastic leukaemia (ALL) (n = 7) and T-cell non-Hodgkin's lymphoma (NHL) (n = 1) presenting within a 5-wk interval were started on a standard induction protocol which included weekly treatment with vincristine for 4 wk. Itraconazole was commenced as antifungal prophylaxis, 1-21 d after the first injection of vincristine. Within 2 to 4 wk, enhanced vincristine neurotoxicity was noted in all patients, abdominal cramps and constipation occurred most frequently, and one patient developed a bowel perforation associated with paralytic ileus. Hyponatraemia associated with SIADH was observed in three patients and four patients developed seizures. An additional patient with B cell NHL developed seizures 5 d after an injection of vincristine. Recovery was complete in all patients and ranged from 2 d to 15 wk.

Conclusion: The extent and consistency of adverse effects documented in this study support the recommendation that concurrent administration of vincristine and itraconazole should be avoided.

MeSH terms

  • Adolescent
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Child
  • Child, Preschool
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Itraconazole / pharmacology*
  • Lymphoma, T-Cell / drug therapy*
  • Neurotoxicity Syndromes / etiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Vincristine / adverse effects*

Substances

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