Itraconazole Oral Solution Enhanced Vincristine Neurotoxicity in Five Patients with Malignant Lymphoma

Abstract

To prevent fungal infections in patients undergoing treatment for hematological malignancies, we investigated the use of oral itraconazole solution as opposed to itraconazole or fluconazole capsules. Herein, we report five lymphoma patients with severe vincristine neurotoxicity in strong association with oral itraconazole solution. Four patients suffered from severe myalgia with or without arthralgia which clinically resembled polymyalgia rheumatica. Two patients suffered from constipation due to subileus and one patient had a severe paralytic ileus. Appropriate management of the above symptoms, which included discontinuation of oral itraconazole solution, resulted in rapid recovery from neurotoxicity. Given the more consistent plasma concentrations of oral itraconazole solution when compared to itraconazole capsules and the ability of itraconazole to interfere with hepatic vincristine metabolism, we strongly recommend avoiding the combined administration of oral itraconazole solution and vincristine.