Evaluation of target attainment of oral posaconazole suspension in immunocompromised children. (19th December 2019)

• Record Type: Journal Article
• Authors: Lai, Tony; Alffenaar, Jan-Willem; Kesson, Alison; Bandodkar, Sushil; Roberts, Jason A
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 75:Number 3(2020)
• Page Start: 726
• Page End: 729
• Publication Date: 2019-12-19
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkz481
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives: To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age. Patients and methods: We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results: A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P <0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions: The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.