Girmenia Corrado, Iori Anna Paola
a Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I , Sapienza University , Rome , Italy.
Expert Opin Drug Saf. 2017 Mar;16(3):329-339. doi: 10.1080/14740338.2017.1273900. Epub 2016 Dec 26.
Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Improvement in the management of IFDs have been achieved with the availability of new effective and safe antifungal drugs, however, many of these newer treatments have some limitations in their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions. Areas covered: This article is an update of a previous review published in this journal evaluating the safety profile of the antifungal drugs. Interesting new features include the availability of the new drug isavuconazole and the new tablet and intravenous formulations of posaconazole. Different dosages and new ways of administration of liposomal Amphotericin B (L-AmB) and echinocandins may be considered in the HSCT practice. Expert opinion: Nephrotoxicity continues to be a clinically relevant and frequent side effect of L-AmB which may cause a reduced clearance of other renally eliminated drugs frequently used in HSCT patients. Echinocandins are favorable therapeutic options in view of their low toxicity and uncommon drug-drug interactions. Important limitations of triazoles are represented by hepatic toxicity and certain side effects particularly after prolonged treatments. The new triazole isavuconazole and the new tablet formulation of posaconazole will be probably increasingly used in the HSCT setting not only due to their efficacy but in particular for their interesting toxicity profile and pharmacokinetic characteristics. The knowledge of these pharmacological findings is crucial in the daily care of allogeneic HSCT patients.
侵袭性真菌病（IFD）是接受异基因造血干细胞移植（HSCT）患者发病和死亡的主要原因。随着新型有效且安全的抗真菌药物的出现，IFD的管理已有所改善，然而，许多这些新疗法在其可变毒性以及药代动力学药物相互作用的独特易感性方面存在一些局限性。涵盖领域：本文是对本杂志之前发表的一篇评估抗真菌药物安全性概况的综述的更新。有趣的新特点包括新药艾沙康唑的上市以及泊沙康唑的新片剂和静脉制剂。在HSCT实践中，可能会考虑脂质体两性霉素B（L-AmB）和棘白菌素不同的剂量和新的给药方式。专家观点：肾毒性仍然是L-AmB临床上相关且常见的副作用，这可能会导致HSCT患者经常使用的其他经肾脏清除的药物清除率降低。鉴于其低毒性和罕见的药物相互作用，棘白菌素是有利的治疗选择。三唑类药物的重要局限性表现为肝毒性和某些副作用，尤其是在长期治疗后。新的三唑类药物艾沙康唑和泊沙康唑的新片剂制剂可能会在HSCT环境中越来越多地使用，这不仅是因为它们的疗效，特别是因为它们有趣的毒性特征和药代动力学特性。了解这些药理学发现对于异基因HSCT患者的日常护理至关重要。
