Therapeutic drug monitoring of posaconazole oral suspension in paediatric hematology patients under 13 years of age.

Background: Posaconazole oral suspension is not approved for use in children younger than 13 years of age, and the optimal dosing regimen is unclear. The target trough concentration of posaconazole for the effective prevention of invasive fungal infections in adults is influenced by multiple factors, but reports in children aged <13 years remain limited. Therefore, the primary objective of this study was to evaluate potential risk factors affecting the steady-state trough concentration of oral posaconazole suspension in a large population of Chinese children.

Methods: This observational, single-center study retrospectively analyzed pediatric patients younger than 13 years of age who received posaconazole oral suspension for the prevention of invasive fungal disease and implemented therapeutic drug monitoring (TDM) from January 2020 to July 2022.

Results: A total of 132 children with 922 steady-state trough concentrations of posaconazole were included in this study. The median dosage of posaconazole by standardized body weight was 14.2 (range, 4.2-51.2) mg/kg/day, with considerable variability. The median posaconazole concentration was 0.81 (range, 0.05-4.5) µg/mL, and the proportion of children reaching the recommended target concentration (≥ 0.7 µg/mL) was 59.5%. The highest percentage of the target concentration (76.8%) was achieved at a median daily dosage of 18 (range, 17-19) mg/kg/day of posaconazole. Multivariate linear regression analysis revealed significant positive correlations between albumin levels (P=0.004) and weight (P<0.001) and posaconazole concentrations. Conversely, treatment with hematopoietic stem cell transplantation (P=0.004), the occurrence of diarrhea (P=0.003), and the coadministration of omeprazole (P<0.001), famotidine (P=0.001) and methylprednisolone (dosage ≥0.7 mg/kg/day) (P=0.006) were associated with significantly reduced posaconazole concentrations.

Conclusions: In children under 13 years of age, administration of a dosage regimen of 18 (range, 17-19) mg/kg/day of posaconazole suspension resulted in a higher proportion of children achieving the recommended target concentration. Multiple factors had significant effects on posaconazole trough concentrations. TDM is important for identifying suboptimal posaconazole exposure and making timely dose adjustments.