학술논문
Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study
Document Type
article
Author
Pierantonio Menna; Francesco Marchesi; Chiara Cattaneo; Anna Candoni; Mario Delia; Gianpaolo Nadali; Alessandra Vatteroni; Crescenza Pasciolla; Salvatore Perrone; Luisa Verga; Daniele Armiento; Maria Ilaria Del Principe; Nicola S. Fracchiolla; Emanuela Salvatorelli; Santina Lupisella; Irene Terrenato; Alessandro Busca; Giorgio Minotti; Livio Pagano
Source
Clinical and Translational Science, Vol 16, Iss 10, Pp 1876-1885 (2023)
Subject
Language
English
ISSN
1752-8062
1752-8054
1752-8054
Abstract
Abstract Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3‐mutated acute myeloid leukemia. Chemotherapy‐induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin‐related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real‐life study to evaluate (i) how often concerns around PCZ‐midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ‐midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p