Retrospective Analysis of Posaconazole Suspension Dosing Strategies in a Pediatric Oncology Population: Single-Center Experience

Mathew, Sherry; Kussin, Michelle L.; Liu, Dazhi; Pozotrigo, Melissa; Seyboth, Brian; Thackray, Jennifer; Yan, Shirley Qiong; Hsu, Meier; Cohen, Nina; Seo, Susan K.

doi:10.1093/jpids/pix058

Cited by 8 publications

(3 citation statements)

References 9 publications

(8 reference statements)

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“…The pharmacokinetics of PCZ in children has not been fully studied to date, and limited information is available on optimal dosing regimen for oral suspension for pediatric patients. Mathew et al examined thirty-two immunocompromised children (aged 3–18 years) receiving PCZ for both prophylaxis and treatment ( Mathew et al, 2017 ). Sixteen of thirty-two patients (50%) achieved target PCZ (0.7 μg mL −1 ) with a median initial dose of 22.8 mg/kg/day (range, 9.2–44 mg/kg/day).…”

Section: Discussionmentioning

confidence: 99%

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

et al. 2022

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Experience in the clinical use of posaconazole (PCZ) in pediatric patients is limited, and no specific dose recommendations exist. This study aimed to investigate an appropriate dosing regimen, and assess the exposure-response relationships of PCZ in children. We reviewed the medical records of inpatients aged <18 years who subjected to PCZ concentrations monitoring. Clinical data, PCZ dosing and monitoring data were collected. A total of 375 PCZ trough concentrations (Cmin) from 105 pediatric patients were included. For children receiving PCZ for prophylaxis, the median doses required to achieve the therapeutic range at the ages of <6, 6–12 and >12 years were 14.80, 14.52 and 12.90 mg/kg/day, respectively (p = 0.001); and for those receiving PCZ for treatment, the median doses were 23.50, 20.96 and 15.38 mg/kg/day, respectively (p = 0.001). Among children taking PCZ for prophylaxis, 12% developed a proven or probable breakthrough IFIs; the median PCZ concentrations were significantly lower than those children with successful treatment response (0.43 versus 1.20 μg mL−1; p < 0.001). 79.2% patients taking PCZ for treatment had a positive clinical response, and the median PCZ concentrations were significantly higher than those children with disease progression (1.06 versus 0.53 μg mL−1; p = 0.024). No association between Cmin values and hepatotoxicity was observed. Factors such as age, CRP, ALT and co-administration with proton pump inhibitors exhibited significant effects on PCZ Cmin. It is necessary to adjust the dosing regimens based on PCZ Cmin to individualize antifungal therapy and provide guidelines for dose adjustment in children.

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Section: Discussionmentioning

confidence: 99%

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

et al. 2022

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“…In children aged ≤ 13 years, a bodyweight-based dosing regimen of the oral suspension of 4 mg/kg TID or body surface area-based regimen of 120 mg/m 2 TID showed a considerable proportion of hematologic children to reach < 0.7 mg/L steady-state plasma concentrations [137][138][139][140]. Therefore, higher initial dosing strategies of ≥ 20 mg/kg/day were recommended and are expected to ensure adequate concentrations [141,142]. Experience with the posaconazole delayed-release tablet in pediatric patients is limited.…”

Section: Pediatricsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Posaconazole

Chen

Krekels

Verweij

et al. 2020

Drugs

112

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Posaconazole is typically used for preventing invasive yeast and mold infections such as invasive aspergillosis in high-risk immunocompromised patients. The oral suspension was the first released formulation and many pharmacokinetic and pharmacodynamic studies of this formulation have been published. Erratic absorption profiles associated with this formulation were widely reported. Posaconazole exposure was found to be significantly influenced by food and many gastrointestinal conditions, including pH and motility. As a result, low posaconazole plasma concentrations were obtained in large groups of patients. These issues of erratic absorption urged the development of the subsequently marketed delayed-release tablet, which proved to be associated with higher and more stable exposure profiles. Shortly thereafter, an intravenous formulation was released for patients who are not able to take oral formulations. Both new formulations require a loading dose on day 1 to achieve high posaconazole concentrations more quickly, which was not possible with the oral suspension. So far, there appears to be no evidence of increased toxicity correlated to the higher posaconazole exposure achieved with the regimen for these formulations. The higher systemic availability of posaconazole for the delayed-release tablet and intravenous formulation have resulted in these two formulations being preferable for both prophylaxis and treatment of invasive fungal disease. This review aimed to integrate the current knowledge on posaconazole pharmacokinetics, pharmacodynamics, major toxicity, existing resistance, clinical experience in special populations, and new therapeutic strategies in order to get a clear understanding of the clinical use of this drug.

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“…17 , revisaron la dosificación de PSC profiláctica en 14 pacientes (edad promedio: 6,7 años) a dosis de 120 mg/mt 2 cada 8 h (equivalente a 12 mg/kg/día), los que alcanzaron un promedio de CP de 0,85 μg/mL, considerado óptimo para la profilaxis, donde la administración de PSC fue con un protocolo para evitar interferencias con otros medicamentos y/o comidas 6,11,19 . Sin embargo, en una revisión de casos pediátricos de V. Bernardo y cols.…”

Section: Artículo Originalunclassified

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico

Valenzuela

García

Barraza

et al. 2018

Rev. chil. infectol.

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Retrospective Analysis of Posaconazole Suspension Dosing Strategies in a Pediatric Oncology Population: Single-Center Experience

Cited by 8 publications

References 9 publications

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

Pharmacokinetics and Pharmacodynamics of Posaconazole

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico

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