Elevated posaconazole trough concentrations are not associated with increased risk for posaconazole toxicity in lung...

Posaconazole is used for prophylaxis and treatment of invasive fungal infections in lung transplant recipients (LTR). Previous studies have not described the relationship between elevated posaconazole trough concentrations and adverse drug reactions in this population.

This IRB-approved, retrospective cohort study at NewYork-Presbyterian Hospital included LTR who had posaconazole trough concentrations measured. The primary aim of this study was to evaluate elevated posaconazole trough concentrations and changes in liver function tests as well as QTc interval. A secondary aim of this study was to identify patient factors associated with elevated posaconazole trough levels.

A total of 109 LTR were included. The average age was 58.1 years (IQR, 48-65), the majority were male (56%). A total of 932 trough levels were assessed with a median number of 8 (IQR, 5-15) levels per patient. The median posaconazole trough concentration was 1.7 mg/L (IQR, 1.1-2.5). Hepatotoxicity, as defined by common terminology criteria for adverse events (CTCAE), was observed in 73.4% of subjects, with the majority classified as grade 1 (67.5%). However, there was no correlation between elevated posaconazole levels and aspartate aminotransferase (r = .03), alanine aminotransferase (r = .04), alkaline phosphatase (r = .04), and total bilirubin (r = .02). There was also no correlation between posaconazole trough concentrations and QTc interval (r = .03).

This analysis demonstrates that no correlation exists between whole blood posaconazole levels and hepatotoxicity or QTc prolongation. Based on these results, posaconazole dose reductions may not be warranted for posaconazole levels that are significantly above the therapeutic target to avert risk for hepatotoxicity or QTc prolongation.