Analysis of posaconazole as oral antifungal prophylaxis in pediatric patients under 12 years of age following allogeneic stem cell transplantation

Abstract

BackgroundPediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of acquiring fungal infections. Antifungal prophylaxis shortly after transplantation is therefore indicated, but data for pediatric patients under 12 years of age are scarce. To address this issue, we retrospectively assessed the safety, feasibility, and initial efficacy of prophylactic posaconazole in children.Methods60 consecutive pediatric patients with a median age of 6.0 years who underwent allogeneic HSCT between August 2007 and July 2010 received antifungal prophylaxis with posaconazole in the outpatient setting. 28 pediatric patients received an oral suspension at 5 mg/kg body weight b.i.d., and 32 pediatric patients received the suspension at 4 mg/kg body weight t.i.d. The observation period lasted from start of treatment with posaconazole until its termination (maximum of 200 days post-transplant).ResultsPediatric patients who received posaconazole at 4 mg/kg body weight t.i.d. had a median trough level of 383 μg/L. Patients who received posaconazole at 5 mg/kg body weight b.i.d. had a median trough level of 134 μg/L. Both regimens were well tolerated without severe side effects. In addition, no proven or probable invasive mycosis was observed.ConclusionPosaconazole was a well-tolerated, safe, and effective oral antifungal prophylaxis in pediatric patients who underwent high-dose chemotherapy and HSCT. Posaconazole at a dosage of 12 mg/kg body weight divided in three doses produced consistently higher morning trough levels than in patients who received posaconazole 5 mg/kg body weight b.i.d. Larger prospective trials are needed to obtain reliable guidelines for antifungal prophylaxis in children after HSCT.

Pharmacokinetics of Posaconazole Oral Suspension in Children Dosed According to Body Surface Area

“…[10][11][12] A prophylactic PSC dosing regimen of 4 mg/kg tid was already proposed to be adequate in allogeneic HSCT patients aged 12 years or younger based on a retrospective clinical trial. 10 Welzen et al even used prophylactic weight-based doses in pediatric patients suffering from chronic granulomatous disease, ranging from 6.1 to 20.6 mg/kg 2 times daily, without significant adverse events. A dose between 12 and 18 mg/kg/d divided in a 3 times daily dosing regimen was also proposed in a nonrandomized, multicenter, open-label, dose-escalation study in pediatric patients aged 17 years or younger.…”

“…8 However, few pharmacokinetic (PK) data in children younger than 13 years are available, resulting in only limited recommendations in current guidelines. 5,[9][10][11][12][13] Little information is available on the correct dosing regimen of the oral suspension in young pediatric patients. [9][10][11][12]14 Similar to what is observed in adults, low PSC plasma concentrations (PPCs) are frequently being measured.…”

“…5,[9][10][11][12][13] Little information is available on the correct dosing regimen of the oral suspension in young pediatric patients. [9][10][11][12]14 Similar to what is observed in adults, low PSC plasma concentrations (PPCs) are frequently being measured. 9,[15][16][17] In this study, we evaluate the PK of a newly introduced dosing regimen for PSC oral suspension, based on the body surface area (BSA), used prophylactically in hematological patients younger than 13 years.…”

Profilaktyka zakażeń grzybiczych u dzieci poddawanych transplantacjom komórek hematopoetycznych

“…przeprowadzili interesujące badanie porównujące 2 różne metody dawkowania pozakonazolu u dzieci <12. rż. (mediana 6 lat) poddawanych allogenicznej HSCT [19]. W latach 2007-2010 60 dzieci po HSCT otrzymywało pozakonazol w dawce 2 Â 5 mg/kg dziennie (28 dzieci) lub 3 Â 4 mg/kg dziennie (32 dzieci).…”

“…Dawki leku były tu znacznie niższe niż w grupie Welzen i wsp. Pomimo faktu, że stężenie leku było mniejsze niż zalecane przez ECIL-4, nie obserwowano IZG ani poważnych objawów ubocznych [19]. W innym badaniu porównującym skuteczność 3 azoli u dzieci stosowanie pozakonazolu w profilaktyce po HSCT zabezpieczyło chorych przez IZG z przeła-mania, podczas gdy takie infekcje wystąpiły podczas przyjmowania itrakonazolu lub worikonazolu.…”