Abstract
BackgroundTherapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability. However, its benefits on clinical outcomes are still being defined. Additionally, TDM data are limited for posaconazole IV and delayed-release tablet formulations among specific patient populations, including critically ill. The aim of this study was to determine the percentage of therapeutic posaconazole and voriconazole drug levels across all formulations in a real-world clinical setting and elucidate factors affecting attainment of target concentrations.MethodsThis study was a retrospective cohort study conducted at the University of Colorado Hospital between September 2006 and June 2015 that evaluated patients who received posaconazole or voriconazole TDM as part of routine care.ResultsVoriconazole (n = 250) and posaconazole (n = 100) levels were analyzed from 151 patients. Of these, 54% of voriconazole and 69% of posaconazole levels were therapeutic. For posaconazole, 14/38 (37%), 28/29 (97%) and 27/33 (82%) levels were therapeutic for the oral suspension, IV, and delayed-release tablet, respectively. Intravenous and delayed-release tablet posaconazole were 20 fold (p < 0.01) and sevenfold (p = 0.002) more likely than the oral suspension to achieve a therapeutic level. Subsequent levels were more likely to be therapeutic after dose adjustments (OR 3.31; 95% CI 1.3–8.6; p = 0.02), regardless of timing of initial non-therapeutic level. In a multivariable logistic regression analysis, no characteristics were independently predictive of therapeutic voriconazole levels and only absence of H2RA/PPI use was independently predictive of therapeutic posaconazole levels. There was no correlation between survival and therapeutic drug levels for either voriconazole (p = 0.67) or posaconazole (p = 0.50).ConclusionsA high percentage of drug levels did not achieve TDM targets for voriconazole and posaconazole oral suspension, supporting the need for routine TDM for those formulations. The utility of TDM for the IV and delayed-release tablet formulations of posaconazole is less apparent.
Highlights
Therapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability
A voriconazole plasma level of 1.0–5.5 or 1.0–6.0 μg/ml is generally recommended as the goal range for improved outcomes and minimized toxicities [11, 12], and a threshold of >0.5–0.7 μg/ml has been recommended as a therapeutic posaconazole concentration [13, 14]
Patients were included in the study if they had received voriconazole or posaconazole and had a drug level drawn for TDM as part of routine clinical care
Summary
Therapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability. Yi et al Ann Clin Microbiol Antimicrob (2017) 16:60 intestinal absorption, drug interactions, diarrhea, chemotherapy, age, and weight [5,6,7,8,9] For both voriconazole and posaconazole, the relationship between efficacy and drug exposure has been established [7, 10, 11]. Given high risk of mortality for invasive fungal disease and the inter- and intra-patient variability in posaconazole and voriconazole pharmacokinetics, therapeutic drug monitoring (TDM) is a strategy employed to optimize drug therapy. As noted in the IDSA guidelines, more studies are needed to look at the benefit of TDM for the intravenous and delayed-release tablet formulations of posaconazole, which has not been well-established
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