Plasma exposures following posaconazole delayed-release tablets in immunocompromised children and adolescents

Author: 

Athanasios Tragiannidis, Heidrun Herbrüggen, Martina Ahlmann, Eleni Vasileiou, Silke Gastine, Heike Thorer, Birgit Fröhlich, Carsten Müller and Andreas H Groll
Journal of Antimicrobial Chemotherapy, dkz359, Published: 27 August 2019

Abstract: 

Background

SADASIVAM Posaconazole is a recommended option for antifungal prophylaxis in paediatric patients >12 years of age. However, little is known about plasma exposures and safety following administration of the delayed-release tablets (DRTs) in children and adolescents.

Methods

In a retrospective observational study, we analysed steady-state trough concentrations of posaconazole in all paediatric patients who had received the DRT formulation between May 2015 and December 2018 for antifungal prophylaxis. Dosing was guided by a published population pharmacokinetic model with weight-based dosing. Drug concentrations in plasma were measured by a validated tandem MS method. Liver function and drug discontinuations due to adverse effects were also assessed.

Results

A total of 34 patients (21 male, 13 female; median age 12 years, range 5–17 years; median body weight 43.5 kg, range 16–84 kg) undergoing treatment for haemato-oncological disorders (n = 23) or immunosuppression for polyarthritis (n = 1) or post-allogeneic HSCT (n = 11) received posaconazole DRTs for a median of 70 days (range 9–391 days). The median first steady-state trough plasma concentration following model-derived dosing was 1607 ng/mL (range 501–8485 ng/mL) with trough concentrations being above the dosing target of ≥700 ng/mL in 32/34 patients (94%). Considering all (first and subsequent) trough concentrations, target attainment was 90% (63/70 samples). Posaconazole was well tolerated without adverse event-related discontinuations or breakthrough infections.

Conclusions

Administration of posaconazole DRTs to paediatric patients guided by a population pharmacokinetic-derived dosing algorithm resulted in predictable and potentially effective exposures and was well tolerated over prolonged time periods.