Azole Therapeutic Drug Monitoring and its Use in the Management of Invasive Fungal Disease

Purpose of review This article summarises the pharmacologic rationale for therapeutic drug monitoring (TDM) of azoles in the management of invasive fungal disease (IFD), explores practical recommendations for TDM guided dosing, discusses barriers to TDM and highlights future directions and challenges to incorporating azole TDM into routine clinical practice. Recent findings Pharmacokinetic studies have demonstrated that significant inter- and intra-patient variability exists in the exposure of azole antifungal agents. This variability can affect treatment success and contribute to toxicity. TDM has been proposed as a tool to individualise azole dosing to optimise efficacy and reduce toxicity. Accounting for significant heterogeneity, there is evolving evidence that TDM improves clinical outcomes for itraconazole, voriconazole and posaconazole. TDM for fluconazole and isavuconazole requires further evaluation. Summary There remains ambiguity over the optimal approach to performing, interpreting, and utilising TDM to improve patient outcomes. This is attributable to a relative lack of literature, operational and logistical challenges to performing TDM.