Treatment of<i>Aspergillus fumigatus</i>infection with posaconazole delayed-release tablets

Shearin, Suzanne; Bell, Tara L

doi:10.2146/ajhp170534

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…A case study of a 13-year-old male patient with CF treated with posaconazole tablets for A. fumigatus infection also demonstrated that plasma trough concentrations of >1 mg/L were attained with a dose of 300 mg, along with improved lung function and eradication of the organism. 24 However, despite these positive experiences thus far, there have been no published pharmacokinetic data to support dosing specific to children with CF, including younger children, and especially in the context of altered pharmacokinetics in this population.…”

Section: Discussionmentioning

confidence: 99%

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Bentley

Davies

Gastine

et al. 2021

Journal of Antimicrobial Chemotherapy

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Objectives To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses. Patients and methods Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function. Results One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients. Conclusions A starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

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Section: Discussionmentioning

confidence: 99%

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Bentley

Davies

Gastine

et al. 2021

Journal of Antimicrobial Chemotherapy

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“…Higher posaconazole concentrations were found to be correlated with lower Aspergillus Immunoglobulin E levels [150]. Posaconazole oral formulations, especially the delayed-release tablet, exhibited satisfactory exposure in children (median age 13 years, range 3-17 years) with CF and was proven to be generally safe and well tolerated [151]. Overall, the posaconazole delayed-release tablet appears to be a suitable antifungal agent in patients with CF due to the improved absorption and wide intrinsic distribution into the lung tissue.…”

Section: Patients With Cystic Fibrosismentioning

confidence: 95%

Pharmacokinetics and Pharmacodynamics of Posaconazole

Chen

Krekels

Verweij

et al. 2020

Drugs

109

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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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“…Описано успешное применение таблетированной формы позаконазола для терапии 13летнего паци ента с муковисцидозом и инфекцией A. fumigatus [104], а также случай эффективной терапии 30летней паци ентки с ОМЛ и необходимостью проведения аллоген ной ТГСК, у которой развился мукормикоз (вызванный Rhizomucor pusillus) с поражением легких и ЦНС. У этой пациентки была проведена хирургическая санация и на значена СПП позаконазола, которая в связи с низкими концентрациями в плазме (0,22 мг/л) была заменена на таблетированную форму позаконазола, которая по зволила достичь достаточных концентраций препарата (> 2 мг/л) при использовании дозы 400 мг/сут, так как стандартная доза 300 мг/сут не обеспечила создание в плазме целевой концентрации (0,45 мг/л) [105].…”

Section: терапия рефрактерных форм игиunclassified

The tablet formulation of posaconazole: clinical pharmacology and the use in patients with hematologic malignancies

Веселов

2020

CMAC

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Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various fungi, including yeast and molds, including Mucorales, what makes a key difference with itraconazole and voriconazole. Clinical studies have demonstrated his efficacy for prophylaxis against invasive fungal infections in hematological patients at high risk (with acute myeloid leukemia, myelodysplastic syndrome, aplastic anemia, and in patients after hematopoietic stem cell transplantation, especially with graft versus host disease). Posaconazole also use as salvage therapy against invasive aspergillosis, mucormycosis and some other systemic mycoses. For today there are 3 posaconazole formulations – oral suspension, modify release tablet and intravenous solution (not registered in Russia at the time of writing this paper). As far as bioavailability of posaconazole following administration by oral suspension is highly variable with low unstable plasma concentrations and there are number of factors with negatively influence to the pharmacokinetic profile of suspension a delayed-release tablet was developed using hot-melt extrusion technology with a pH-sensitive polymer. The tablet formulation releases the drug in the intestine, and this leads to the enhanced bioavailability and increased posaconazole exposure parameters and, as a result, to a higher efficacy. This was demonstrated in pre-clinical, early phase clinical studies and confirmed with data from real practice. The tablet formulation has well tolerability profile with a low incidence of clinically significant adverse events. For today posaconazole included in all relevant clinical recommendations with high levels of evidence, including prophylaxis of invasive mycoses and therapy of their refractory forms, while the authors agree that for the oral therapy a preference should be given to the tablet formulation of posaconazole.

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Treatment ofAspergillus fumigatusinfection with posaconazole delayed-release tablets

Abstract: A 13-year old patient with CF was successfully treated for an infection with posaconazole delayed-release tablets.

Cited by 4 publications

References 13 publications

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Pharmacokinetics and Pharmacodynamics of Posaconazole

The tablet formulation of posaconazole: clinical pharmacology and the use in patients with hematologic malignancies

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