Potentiation of vincristine toxicity by itraconazole in children with lymphoid malignancies.
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.


CONCLUSIONS
The extent and consistency of adverse effects documented in this study support the recommendation that concurrent administration of vincristine and itraconazole should be avoided.
Kamaluddin
M
M
Department of Haematology Oncology, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
McNally
P
P
Breatnach
F
F
O'Marcaigh
A
A
Webb
D
D
O'Dell
E
E
Scanlon
P
P
Butler
K
K
O'Meara
A
A
D000293:Adolescent; D000935:Antifungal Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D014750:Vincristine / Q000009:adverse effects*
D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D017964:Itraconazole; D014750:Vincristine