Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age

a retrospective analysis and literature review

T. Jancel, P. A. Shaw, C. W. Hallahan, T. Kim, A. F. Freeman, S. M. Holland, Scott Robert Penzak

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

What is known and objective: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). Methods: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. Results and discussion: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8–10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. What is new and conclusions: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalJournal of Clinical Pharmacy and Therapeutics
Volume42
Issue number1
DOIs
StatePublished - 1 Feb 2017

Fingerprint

Drug Monitoring
Suspensions
Pediatrics
posaconazole
Chronic Granulomatous Disease
Triazoles
Mycoses
National Institutes of Health (U.S.)
United States Food and Drug Administration
Fungi
Therapeutics
Yeasts
Body Weight

Keywords

  • paediatric
  • pharmacokinetics
  • posaconazole
  • therapeutic drug monitoring

Cite this

Jancel, T. ; Shaw, P. A. ; Hallahan, C. W. ; Kim, T. ; Freeman, A. F. ; Holland, S. M. ; Penzak, Scott Robert. / Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age : a retrospective analysis and literature review. In: Journal of Clinical Pharmacy and Therapeutics. 2017 ; Vol. 42, No. 1. pp. 75-79.
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abstract = "What is known and objective: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). Methods: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. Results and discussion: A total of 20 male patients were included, of whom 15 (75{\%}) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8–10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95{\%}, 60{\%} and 25{\%} of patients, respectively. What is new and conclusions: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.",
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Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age : a retrospective analysis and literature review. / Jancel, T.; Shaw, P. A.; Hallahan, C. W.; Kim, T.; Freeman, A. F.; Holland, S. M.; Penzak, Scott Robert.

In: Journal of Clinical Pharmacy and Therapeutics, Vol. 42, No. 1, 01.02.2017, p. 75-79.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age

T2 - a retrospective analysis and literature review

AU - Jancel, T.

AU - Shaw, P. A.

AU - Hallahan, C. W.

AU - Kim, T.

AU - Freeman, A. F.

AU - Holland, S. M.

AU - Penzak, Scott Robert

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N2 - What is known and objective: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). Methods: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. Results and discussion: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8–10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. What is new and conclusions: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.

AB - What is known and objective: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD). Methods: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy. Results and discussion: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8–10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively. What is new and conclusions: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.

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