Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients:Factors affecting trough plasma concentrations

Objectives: This study describes therapeutic drug monitoring (TDM) of posaconazole suspension and modified release (MR) tablets in lung transplant (LTx) recipients and evaluates factors that may affect posaconazole trough plasma concentration (C min ). Methods: A single-centre, retrospective study evaluating posaconazole C min in LTx recipients receiving posaconazole suspension or MR tablets between January 2014 and December 2016. Results: Forty-seven LTx patients received posaconazole suspension, and 78 received the MR tablet formulation; a total of 421 and 617 C min measurements were made, respectively. Posaconazole was concurrently administered with proton pump inhibitor in≥90% of patients. The median (IQR) of initial posaconazole C min following 300 mg daily of posaconazole tablet was significantly higher than that of 800 mg daily of posaconazole suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P<0.01]. Variability in posaconazole C min was apparent regardless of the formulations prescribed and dose adjustments were routinely undertaken to maintain therapeutic C min . A clear dose-response relationship was observed in patients receiving posaconazole MR tablets. Non-specific adverse events (fatigue, tremor, lethargy, sweating, nausea/vomiting and weight loss) were reported in 3/78 (4%) patients receiving posaconazole MR tablets. Posaconazole C min in these three patients was determined to be 9.6, 6.2 and 2.3 mg/L. Conclusions: The current study has provided clinically important insights into the TDMof posaconazole in LTx recipients. Routine TDMshould be undertaken in LTx recipients receiving posaconazole suspension and/orMR tablets.