Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, Via Benevento 6, 00161 Rome, Italy.
Expert Opin Drug Saf. 2012 Sep;11(5):803-18. doi: 10.1517/14740338.2012.712111.
Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Considerable progress in treating IFDs has been achieved over the last years, through the availability of new, effective drugs. However, many of these newer antifungal agents have some limitations, such as their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions.
This article reviews the literature evaluating the safety profile of the lipid formulations of Amphotericin B, echinocandins, and second-generation triazoles. It also discusses the possible drug-drug interactions with some drugs commonly used in allogeneic HSCT.
Nephrotoxicity is the most frequent side effect of lipid formulations of Amphotericin B, which may cause a reduced clearance of the renally eliminated calcineurin inhibitors used for the control of Graft Versus Host Disease. Second-generation triazoles are characterized by a limited toxicity profile, but also by frequent drug-drug interactions with other drugs metabolized by the hepatic enzymes. The echinocandins are characterized by a very low toxicity profile and negligible interactions with other drugs. Such pharmacological knowledge is crucial in the daily care of allogeneic HSCT patients.
侵袭性真菌病(IFD)是异基因造血干细胞移植(HSCT)患者发病率和死亡率的主要原因。近年来,通过使用新型有效药物,在治疗 IFD 方面取得了相当大的进展。然而,许多这些新型抗真菌药物存在一些局限性,例如它们的毒性不同和对药代动力学药物相互作用的独特易感性。
本文综述了评估两性霉素 B 脂质制剂、棘白菌素类和第二代三唑类药物安全性概况的文献。还讨论了与异基因 HSCT 中常用的一些药物可能发生的药物-药物相互作用。
两性霉素 B 脂质制剂最常见的副作用是肾毒性,这可能导致用于控制移植物抗宿主病的经肾脏清除的钙调神经磷酸酶抑制剂清除率降低。第二代三唑类药物的特点是毒性谱有限,但也与其他经肝酶代谢的药物经常发生药物-药物相互作用。棘白菌素类的特点是毒性谱极低,与其他药物的相互作用可忽略不计。这些药理学知识对于异基因 HSCT 患者的日常护理至关重要。