Implementation and outcomes of a therapeutic drug monitoring program for antifungal and antiretroviral agents in a tertiary medical center in Taiwan

Abstract

AbstractIntroductionTherapeutic drug monitoring (TDM) of antifungal and antiretroviral agents was recently initiated at National Taiwan University (NTU) Hospital based on a collaboration between clinicians at NTU Hospital and faculty at the NTU School of Pharmacy since 2009. Interim analyses were conducted to evaluate its effects on treatment outcomes.ObjectivesThe purpose of this study was to establish and evaluate the impact of the TDM service on effectiveness and safety over a 10‐year period.MethodsThe TDM program was initiated as a research‐based pharmacy service. This prospective observational study enrolled all patients who were prescribed voriconazole, posaconazole, and efavirenz. Three interim analyses were conducted: (1) Identification of the cutoff points of voriconazole plasma concentrations associated with hepatotoxicity and hallucinations during 2009‐2010, (2) Examination of whether TDM‐guided posaconazole dosing adjustment increased the target attainment of plasma concentrations and the response rate during 2012‐2013, and (3) Evaluation of the clinical outcomes of TDM‐guided efavirenz dosing regimens during 2009‐2016.ResultsTDM of voriconazole, posaconazole, and efavirenz was performed in 792, 237, and 901 patients, respectively. Voriconazole trough concentration was associated with hepatotoxicity and hallucinations in 40 patients. Trough concentrations above 4.5 mcg/mL may increase the risk of hepatotoxicity. Adverse events and response rates were improved by TDM followed by dosing adjustment. TDM‐guided posaconazole dosing adjustment increased the target attainment of trough concentrations and the response rate in 41 patients. The mid‐dosing concentration of efavirenz in 171 patients was 2.82 mcg/mL (range: 0.98‐10 mcg/mL) during the initial monitoring period (2009‐2012). A TDM‐guided half‐dose regimen containing efavirenz tested on 203 patients in 2013‐2016 mitigated adverse events while maintaining effectiveness.ConclusionThe interim analyses of this TDM service demonstrated an improvement in the quality of care and favorable outcomes in the treatment of fungal and HIV infections.