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Review
. 2019 Nov;15(11):881-895.
doi: 10.1080/17425255.2019.1671971. Epub 2019 Oct 30.

Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients

Jamie John  1 , Angela Loo  1 , Shawn Mazur  1 , Thomas J Walsh  2
Affiliations
Review

Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients

Jamie John et al. Expert Opin Drug Metab Toxicol. 2019 Nov.

Abstract

Introduction: Therapeutic drug monitoring (TDM) has been shown to optimize the management of invasive fungal infections (IFIs), particularly for select antifungal agents with a well-defined exposure-response relationship and an unpredictable pharmacokinetic profile or a narrow therapeutic index. Select triazoles (itraconazole, voriconazole, and posaconazole) and flucytosine fulfill these criteria, while the echinocandins, fluconazole, isavuconazole, and amphotericin B generally do not do so. Given the morbidity and mortality associated with IFIs and the challenges surrounding the use of currently available antifungal agents, TDM plays an important role in therapy.Areas covered: This review seeks to describe the rationale for TDM of antifungal agents, summarize their pharmacokinetic and pharmacodynamic properties, identify treatment goals for efficacy and safety, and provide recommendations for optimal dosing and therapeutic monitoring strategies.Expert opinion: Several new antifungal agents are currently in development, including compounds from existing antifungal classes with enhanced pharmacokinetic or safety profiles as well as agents with novel targets for the treatment of IFIs. Given the predictable pharmacokinetics of these newly developed agents, use of routine TDM is not anticipated. However, expanded knowledge of exposure-response relationships of these compounds may yield a role for TDM to improve outcomes for adult and pediatric patients.

Keywords: Antifungal agent; antifungal dose modification; flucytosine; invasive fungal infection; itraconazole; pediatrics; pharmacodynamics; posaconazole; therapeutic drug monitoring; voriconazole.

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