Itraconazole-Enhanced Vindesine Neurotoxicity in Adult Acute Lymphoblastic Leukaemia.

Severe neurotoxicity following treatment with itraconazole and vincristine has been reported in 25 patients. Here we presented two adult acute lymphoblastic leukemia (ALL) patients developed neurotoxicity after treated with itraconazole and another vinca alkaloids, vindesine. Case 1: A 20-year-old male was diagnosed as having ALL and achieved complete remission (CR) after induction chemotherapy with DVP. He was treated with Hyper-CVAD for consolidation. Because he has a history of pulmonary invasive fungal infection, antifungal prophylaxis with itraconazole solution was started. Nine days after itraconazole was started, some symptom and signs of paralytic ileus were presented. He was diagnosed to have paralytic ileus secondary to neurotoxicity caused by itraconazole and vindesine. After the itraconazole was stopped, his paralytic ileus was improved rapidly. Case 2: A 37-year-old female was diagnosed as having ALL. A diagnosis of B-cell/T-cell biphenotypic acute leukemia was established based on the results of flow cytometry analysis. She was commenced on induction chemotherapy as for ALL (dexamethasone, Idarubicin, and vindesine). The patient presented as pulmonary infection with fever, cough, and expectoration in day 9. Emperical antifungal treatment with itraconazole injection was initiated. Five days after itraconazole injection was started, some symptom of neurotoxicity including limbs anesthesia, and paralytic ileus were presented. After the itraconazole and vindesine were discontinued, these symptoms were resolved. Given the interaction of itraconazole with vinca alkaloids leading to severe and even potentially fatal toxicities, the combination use of these drugs should be avoided.