Itraconazole-Related Increased Vincristine Neurotoxicity

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Abstract
Itraconazole is particularly attractive in fungal prophylaxis for cancer patients due to its broad spectrum, including Candida and Aspergillus. It is generally well tolerated. However, its efficacy in preventing invasive aspergillosis could not be demonstrated. A 3-year-old boy diagnosed with acute lymphoblastic leukemia received induction chemotherapy. On day 14, itraconazole solution at a dose of 5 mg/kg was begun. Ten days after itraconazole was started, he developed paralytic ileus, neurogenic bladder, mild left ptosis, and absence of deep reflexes, with severe paralysis of the lower extremities and mild weakness of the upper extremities. Itraconazole withdrawal was followed by rapid improvement, with neurologic examination returning to normal within 6 weeks. Nineteen cases of unusual enhanced vincristine neurotoxicity related to itraconazole have been reported in children. Although the manifestations are the same as those usually associated with the use of vincristine, in these cases the severity appears remarkable. The authors suggest that in the absence of any proven benefit of itraconazole prophylaxis, and given the interaction of this drug with vincristine leading to severe and even potentially fatal toxicities, the combination use of these drugs should be avoided.