Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age: a retrospective analysis and literature review

Abstract

What is Known and Objective Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and molds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in pediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). Methods This retrospective single-center study reviewed pediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment of fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. Results and Discussion A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6.5 years (range: 2.8 – 10.7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n=8) or treatment (n=12). Posaconazole dose referenced to total body weight ranged from 10.0 – 49.2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700, and ≥1250 ng/mL in 95, 60, and 25% of patients, respectively. What is New and Conclusions Patients younger than 13 years of age had highly variable trough concentrations and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.

Pharmacokinetics and Pharmacodynamics of Posaconazole

“…High variability in posaconazole concentrations was also reported in the pediatric population as a result of the erratic bioavailability for which TDM was recommended [138][139][140][141]143]. Consistent with the previous findings in adults [37][38][39], diarrhea and concomitant PPI use also had a negative impact on the bioavailability of the suspension in children [70].…”

Successful outcome of disseminated mucormycosis in a 3-year-old child suffering from acute leukaemia: the role of isavuconazole? A case report

“…However, neither posaconazole nor ISAV drug are currently approved for paediatric use. Only an oral suspension posaconazole has been tested in children and this resulted in high inter-and intra-patient variability in serum concentrations [16]. An intravenous formulation was not available in France at that time.…”

Advances in the Treatment of Mycoses in Pediatric Patients

“…In this study, the use of posaconazole as a suspension or tablet had similar efficacy, but patients who received a posaconazole tablet achieved much earlier the targeted plasma concentration than those who received the suspension formulation [38]. Posaconazole has also been used in patients with primary immunodeficiencies, including chronic granulomatous disease (CGD) [36]. Although a daily dose of 120 mg/m 2 body surface given in three doses has been proposed for oral posaconazole suspension [37], the optimal dosage needs to be further studied in children, including the new formulation [39].…”