Posaconazole Plasma Monitoring in Immunocompromised Children

McMahon, Jessica; Théôret, Yves; Autmizguine, Julie; Bittencourt, Henrique; Tapiéro, Bruce; Ovetchkine, Philippe

doi:10.1093/jpids/piw087

Cited by 10 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High variability in posaconazole concentrations was also reported in the pediatric population as a result of the erratic bioavailability for which TDM was recommended [138][139][140][141]143]. Consistent with the previous findings in adults [37][38][39], diarrhea and concomitant PPI use also had a negative impact on the bioavailability of the suspension in children [70].…”

Section: Pediatricssupporting

confidence: 79%

“…A twice-daily allometric dosing algorithm based on bodyweight (index at 0.75) resulted in adequate posaconazole concentrations at day 10 in 12 children aged 3-16 years with chronic granulomatous disease [136]. 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].…”

Section: Pediatricsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and Pharmacodynamics of Posaconazole

Chen

Krekels

Verweij

et al. 2020

Drugs

128

View full text Add to dashboard Cite

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.

show abstract

Section: Pediatricssupporting

confidence: 79%

Section: Pediatricsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Posaconazole

Chen

Krekels

Verweij

et al. 2020

Drugs

128

View full text Add to dashboard Cite

show abstract

“…Interestingly, the rate of achievement of the optimal trough level of PPC did not change significantly at the second and third assessment in the prophylaxis group. This finding can be explained by the saturable kinetics of absorption of posaconazole so that drug concentrations are expected to be stable across the dosing levels; also by the fact that the other potentially corrective actions, such as dividing the daily dosage into 4 administrations, administration concomitant with higher-fat meals, or the elimination of concomitant PPI or anti-H2 receptor drugs, were left to the discretion of the patient's physician and not uniformly applied during the study.The only factor significantly associated with the achievement of the recommended PPC trough level was the use of PPI, whereas other factors such as gender, age, and type of treatment (chemotherapy or HSCT) did not have any impact, as recently reported 22. The issue of the exact pediatric dosage is still a matter of investigation.…”

mentioning

confidence: 87%

Posaconazole oral dose and plasma levels in pediatric hematology‐oncology patients

Vicenzi

Calore

Decembrino

et al. 2018

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…thus, the monitoring of trough concentrations in children is of the utmost importance for PCZ therapeutic effectiveness and safety ( Jancel et al, 2017 ; Boonsathorn et al, 2019 ). There is an agreement that children need higher and personalized doses to reach therapeutic C min ( McMahon et al, 2017 ; Lai et al, 2020 ). It is difficult to attain the target concentration of PCZ for children and there is a significant variability in the dose required because of its unpredictable bioavailability ( Gwee et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Posaconazole Plasma Monitoring in Immunocompromised Children

Cited by 10 publications

References 12 publications

Pharmacokinetics and Pharmacodynamics of Posaconazole

Pharmacokinetics and Pharmacodynamics of Posaconazole

Posaconazole oral dose and plasma levels in pediatric hematology‐oncology patients

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients

Contact Info

Product

Resources

About