Posaconazole delayed‐release tablets in paediatric haematology–oncology patients

Abstract

| INTRODUC TI ONInvasive fungal infections (IFIs) represent a major cause of morbidity and mortality in high-risk paediatric haematology-oncology patients. [1][2][3] Posaconazole is a broad-spectrum triazole approved for patients ≥13 years (≥18 years in Europe) as oral and intravenous formulation. Two oral formulations are approved: suspension and tablet. The oral suspension has a variable bioavailability depending on gastric pH and the type of concomitant meal. 4,5 Differently from suspension, Summary Background: To date, there are few studies that describe pharmacokinetics, safety and efficacy of posaconazole delayed-release tablet (DRT) formulation in the paediatric population. Objectives: We evaluated retrospectively posaconazole plasma concentrations and safety of posaconazole DRT in paediatric haematology-oncology patients. Patients and methods: Posaconazole DRT was assessed in 28 haematological paediatric patients with a median age 15 of years (range 5-18) and a median body weight of 50 kg (range 22-83 kg). Twenty-one patients received posaconazole DRT as prophylaxis and 7 patients as therapy.Results: As prophylaxis, the median daily dose was 5.5 mg/kg/day (range 2.2-22.2) with posaconazole trough level ≥ 0.7 μg/mL in 80% by first week, 62.5% by second week and 87.5% by fourth week. As therapy, the median daily dose was 4 mg/kg/day (range 3.3-4.5) with trough level ≥ 1 μg/mL 100% by first week, 80% by second week and 33.4% by fourth week. Conclusions: Posaconazole DRT is feasible in paediatric patients capable to swallow tablets. Specific pharmacokinetic studies are needed. K E Y W O R D S antifungal agents, antifungal target, deep fungal infection, paediatric malignancy, posaconazole, posaconazole delayed-release tablet (DRT)

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

“…8,186 Therefore, TDM is indicated for patient groups at risk of low exposure who are receiving prophylaxis with the new posaconazole tablet formulation (e.g. patients with cystic fibrosis, 187 presence of graft-versus-host disease, 10,181 drug-drug interactions including those on concurrent corticosteroids and proton pump inhibitors, 10,188 obese patients, 189,190 young children [191][192][193][194] and patients with gastrointestinal complications including diarrhoea 10,190,195,196 ).…”

A Population Pharmacokinetic Modeling and Simulation Study of Posaconazole Oral Suspension in Immunocompromised Pediatric Patients: A Short Communication

“…For an invasive infection, rapid attainment of the PK/PD target is warranted, thereby favoring the use of the tablet or intravenous formulation. 7,42,43 Population modeling of a larger dataset, including rich sampling and including patients administered different formulations, is required to achieve well-informed dose-finding for immunocompromised children.…”

Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021

“…In keeping with the adult literature, the administration of posaconazole modified-release tablets is associated with superior attainment of therapeutic levels in children compared to oral suspension. 100,116,[158][159][160] Attainment of target level (>700 ng/mL) in 94% (32/34) of children receiving modified-release tablets using weight-banded dosing has been reported (Table 7). 116 In two small studies of IV posaconazole for IFD prophylaxis, attainment of target levels was reported in 95-100% of children using doses of 6-7 mg/kg/day.…”