Antifungal management in the era of novel targeted therapy

Abstract

 With the exploration of genomic and molecular landscape of hematological malignancies, and the identification of key mutations driving their pathogenesis, novel targeted agents have been rapidly incorporated into the other different classes of therapeutic agents including conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). With the expansion of therapeutic options, hematologists are increasingly required to adapt their clinical practices to maximize the efficacy of novel therapies while minimizing treatment-related toxicities. Many of these novel targeted agents are metabolized by the cytochrome P450 system, necessitating careful evaluation of potential drug-drug interactions (DDIs) in clinical practice. This is particularly relevant for pharmacokinetic interactions with triazole antifungals, which are moderate to strong CYP3A4 inhibitors. This is particularly relevant for pharmacokinetic interactions with triazole antifungals, which are moderate to strong CYP3A4 inhibitors. The co-administration of triazoles with targeted agents (e.g., venetoclax, gilteritinib, quizartinib), can increase their exposure, presenting a challenge for clinicians. In this review, we will discuss strategies to manage these interactions in the specific clinical setting of concomitant administration of novel anti-leukemia agents and triazoles, and also discuss how to adjust the dosage of anti-leukemic agents, immunosuppressants, and the novel graft-versus-host disease (GVHD) agents when used in combination with triazoles.