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《2014年优化抗真菌药物给药与监测以避免血液系统恶性肿瘤患者毒性反应并改善预后的共识指南》

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy, 2014.

作者信息

Chau M M, Kong D C M, van Hal S J, Urbancic K, Trubiano J A, Cassumbhoy M, Wilkes J, Cooper C M, Roberts J A, Marriott D J E, Worth L J

机构信息

Pharmacy Department, The Royal Melbourne Hospital, Melbourne Health, Parkville, Victoria.

出版信息

Intern Med J. 2014 Dec;44(12b):1364-88. doi: 10.1111/imj.12600.

Abstract

Antifungal agents may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non-compliance, non-linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed.

摘要

抗真菌药物可能会导致严重的毒性反应或药物相互作用,进而使血液系统恶性肿瘤患者的抗真菌药物浓度低于治疗水平,并导致较差的临床预后。通过临床评估、实验室监测、避免特定药物组合以及调整剂量,可将这些风险降至最低。可能还需要采取一些具体措施,比如确定口服药物相对于进餐的最佳给药时间、进行预先补液和补充电解质。对抗真菌药物进行治疗药物监测(TDM)是必要的,尤其是在出现不依从、非线性药代动力学、吸收不足、治疗窗狭窄、疑似药物相互作用或意外毒性的情况下。本文提供了伏立康唑和泊沙康唑TDM在血液病患者临床管理中的推荐适应症。随着对药物基因组学对唑类药物(尤其是伏立康唑)代谢影响的认识不断深入,本文提出了药物基因组学评估在临床实践中的潜在应用。

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