Pharmacokinetics, Safety, and Tolerability of Caspofungin in Children and Adolescents

Abstract

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m 2 /day or 70 mg/m 2 /day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC 0-24 ) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m 2 /day (maximum, 70 mg/day), the AUC 0-24 following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC 0-24 and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m 2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m 2 /day provides a comparable exposure to that of adult patients treated with 50 mg/day.

Efficacy and safety of caspofungin in children: systematic review and meta-analysis

“…7 In this study, caspofungin was more effective and the incidence of adverse events was lower, results similar to the findings of other pediatric studies [12][13][14] and those of Mora et al, who studied the use of this drug in adult patients with invasive candidiasis. 15 At a higher level of evidence, the systematic review by Falagas et al, 16 about adolescent and adult patients, in which, in agreement with our observations in the pediatric stage, they conclude that caspofungin could be an alternative agent in the treatment of invasive candidiasis y candidiasis esophagitis, since it has the same efficacy and less toxicity, without any changes in the mortality rate, as stated in other reports.…”

Caspofungin for the treatment of azole resistant candidemia in a premature infant

“…3 A scheme based on body-surface area dosing (maintenance dose of 50 mg/m 2 /day) was found to better approximate levels of adults given 50 mg/day. Unfortunately, pharmacokinetic data for caspofungin in infants are nonexistent as of this writing.…”

Invasive aspergillosis in children after haematopoietic stem cell transplantation

“…Współczesna Onkologia (2010) vol. 14; 1 (44)(45)(46)(47)(48)(49)(50)(51)(52)(53) wysoką śmiertelnością. Aspergiloza inwazyjna może wystąpić w okresie neutropenii, jednak obecnie częściej obserwuje się późną aspergilozę, powyżej 40. dnia po allo-HSCT, związaną z leczeniem immunosupresyjnym choroby przeszczep przeciwko gospodarzowi (graft versus host disease -GVHD) [8].…”

“…Aktualnie dostępne są 3 preparaty echinokandyn: kaspofungina, mikafungina i anidulafungina, przy czym zarejestrowane są kaspofungina i mikafungina. W badaniach farmakokinetycznych, bezpieczeństwa i tolerancji kaspofunginy wykazano, że dawka 50 mg/m 2 p.c./dobę u dzieci o powierzchni ciała do 1 m 2 jest ekwiwalentem dawki 50 mg/dobę u dorosłych, przy czym maksymalną dawką dobową jest 70 mg [44]. Wykazano, że również dawkowanie kaspofunginy 1 mg/kg/dobę zapewnia wysoką skuteczność przeciwgrzybiczą u pacjentów w immunosupresji [45].…”

“…14; 1 (44)(45)(46)(47)(48)(49)(50)(51)(52)(53) Inwazyjna aspergiloza u dzieci po transplantacji komórek hematopoetycznych Wstęp W ciągu ostatnich lat, wraz z postępem w leczeniu chorób nowotworowych układu krwiotwórczego, obserwuje się wzrost występowania układo-wych zakażeń grzybiczych, a w szczególności inwazyjnej aspergilozy (invasive aspergillosis -IA) [1]. Pomimo wprowadzenia do terapii nowych leków przeciwgrzybiczych, skuteczność leczenia grzybicy inwazyjnej (invasive fungal infection -IFI) wynosi ok. 50%, a śmiertelność w grupie chorych poddanych transplantacji alogenicznych komórek hematopoetycznych (hematopoetic stem cell transplantation -HSCT) sięga 90% [2].…”