Résumé
Background: Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13years 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 >= 700ng/mL in immunocompromised children <13years of age.
Patients and methods: We performed a retrospective study of immunocompromised children <13years of age receiving posaconazole suspension prophylaxis at a starting dose of 5mg/kg every 8h for >= 7days and who had a posaconazole concentration measured after >= 7days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded.
Results: A total of 70 patients were included with a median age of 5years (range 3months to 12years). The mean posaconazole plasma concentration was 783.4ng/mL (IQR 428.3-980ng/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 H-2 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 1069.8ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70).
Conclusions: The studied 5mg/kg posaconazole suspension every 8h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.