Initial posaconazole dosing to achieve therapeutic serum posaconazole concentrations among children, adolescents, and young adults receiving delayed-release tablet and intravenous posaconazole.

Abstract

Posaconazole is a broad-spectrum antifungal used for prophylaxis and treatment of invasive fungal diseases. There are limited data on the optimal dosing, safety, and efficacy of the DRT and IV formulations in immunocompromised pediatric and adolescent patients. We describe our experience including dosing, plasma trough concentrations, safety, and tolerability. Plasma concentrations ≥.7µg/mL were considered therapeutic for prophylaxis and ≥1.0µg/mL for treatment. Fifty-four patients (median age of 16years) received DRT or IV formulations of posaconazole. Thirty-one (57%) patients received posaconazole for treatment and 23 (43%) for prophylaxis. Overall, 36 (67%) patients achieved targeted initial plasma trough concentrations (median 1.3µg/mL) (Figure1). The median daily dose among patients <13years of age who achieved the targeted initial concentrations was 7.3mg/kg/day for the DRT formulation and 9.8mg/kg/day for the IV formulation. The median daily dose among patients ≥13years of age who achieved the targeted initial concentrations was 4.9mg/kg/day for the DRT formulation and 5.6mg/kg/day for the IV formulation. Thirty-six patients (67%) developed transaminitis, mostly grade 1. Our observations show that DRT and IV formulations are safe and effective in immunocompromised children, adolescents, and young adults. Higher dosing per body weight of DRT and IV posaconazole may be required in patients <13years of age compared with patients 13years of age and older to achieve therapeutic plasma concentrations. [Figure: see text].