Abstract
BackgroundPosaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs).MethodsBibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA).ResultsTwenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09–3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94–3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings.ConclusionsAn optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L.
Highlights
Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice
Our pooled analysis demonstrated that a steady-state posaconazole target of ≥0.5 mg/L is more predictive for successful prophylaxis than the target of ≥0.7 mg/L
[24] The evidence of the recommendation from Food and Drug Administration (FDA) is based on a Randomized controlled trial (RCT) trial in high risk patients with graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation and the results showed that the successful prophylactic rate would be 98.1% when patients’ posaconazole average concentration reached over 0.7 mg/L, which is similar to our outcome (95.8%) [12, 21]
Summary
Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. Posaconazole is a second-generation triazole agent with antifungal activity against a wide range of yeasts (candida species) and molds (Aspergillus species, Zygomycetes, and Fusarium species) [3, 4]. It has been strongly recommended as a prophylaxis of IFIs by guidelines from IDSA and ESCMID with high-quality evidence [5,6,7]. Due to the large interindividual variability in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised by IDSA and FDA in order to ensure adequate exposure and optimize clinical efficacy for posaconazole suspension [5, 8, 9]
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