Chau Maggie M, Daveson Kathryn, Alffenaar Jan-Willem C, Gwee Amanda, Ho Su Ann, Marriott Deborah J E, Trubiano Jason A, Zhao Jessie, Roberts Jason A
Pharmacy Department, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Infectious Diseases and Microbiology, The Canberra Hospital, Garran, Australian Capital Territory, Australia.
Intern Med J. 2021 Nov;51 Suppl 7:37-66. doi: 10.1111/imj.15587.
Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure-response relationship with either a narrow therapeutic window, large dose-exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non-compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM-guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided.
抗真菌药物的给药方式可能很复杂,且存在药物相互作用的可能性,这两者都可能导致血液系统恶性肿瘤患者和造血干细胞移植受者的抗真菌药物浓度低于治疗水平,并使临床预后变差。当药物浓度过高时,抗真菌药物也可能会产生显著的毒性。通过临床评估、实验室监测、避免使用相互作用的药物以及调整剂量,可以将给药不足的情况降至最低。治疗药物监测(TDM)在抗真菌治疗中发挥着越来越重要的作用,特别是对于那些具有明确的暴露-反应关系的抗真菌药物,这些关系包括治疗窗狭窄、剂量-暴露变异性大、影响药物代谢的细胞色素P450基因多态性、存在抗真菌药物相互作用或意外毒性,和/或存在口服抗真菌药物不依从或吸收不足的问题。本指南提供了关于选定抗真菌药物的抗真菌药物监测和TDM指导的剂量调整建议,并包括用于识别和分析抗真菌药物相互作用的推荐资源。还提供了抗真菌TDM最佳解读和剂量建议的推荐能力要求。