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Posaconazole therapeutic drug monitoring in pediatrics: a single-center retrospective study
Khalid W Taher1, Razan Almofada2, Hala Hijazi2
1Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354,, MBC 11, Riyadh, 11211, Saudi Arabia. wtkhalid@kfshrc.edu.sa.
Insights
Posaconazole dosing in children shows variable concentrations, with about half achieving therapeutic targets. Further research is needed to optimize posaconazole use in pediatric invasive fungal infections.
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Invasive fungal infections (IFIs) pose significant risks in immunosuppressed children.
- Posaconazole is a key antifungal agent for prophylaxis and treatment.
- Optimizing posaconazole therapy is crucial for improving pediatric patient outcomes.
Purpose of the Study:
- To determine the percentage of pediatric patients achieving therapeutic posaconazole trough concentrations.
- To explore factors influencing posaconazole exposure, including dose and patient characteristics.
- To evaluate the relationship between posaconazole levels and clinical outcomes or toxicity.
Main Methods:
- Retrospective analysis of 42 pediatric patients (1 month to 18 years) receiving posaconazole.
- Collection of data on patient demographics, posaconazole dosing, and trough concentrations.
- Assessment of factors affecting trough levels, such as drug interactions and laboratory values.
Main Results:
- 59.5% of initial posaconazole trough concentrations were within the therapeutic range.
- Mean initial trough concentration was 1.4 mg/L, with significant variability.
- 23.8% of patients experienced adverse events potentially related to posaconazole.
Conclusions:
- Posaconazole trough concentrations exhibit considerable variability in pediatric patients.
- Approximately half of pediatric patients achieved target concentrations with initial dosing.
- Posaconazole demonstrated a favorable safety profile with minimal adverse events reported.
Background:
Invasive fungal infections are associated with high morbidity and mortality in immunosuppressed pediatric patients. Posaconazole is commonly used for both prophylaxis and treatment of invasive fungal infections. The study's primary objective was to determine the percentage (%) of patients that achieved posaconazole therapeutic targets. The secondary objective was to evaluate the relationship between posaconazole exposure and clinical outcomes or toxicity.
Methods:
This single-center retrospective study included pediatric patients from 1 month to 18 years who received posaconazole for prophylaxis fungal infections. Data were collected from the hospital's electronic medical records and included age, gender, height, weight, laboratory values, dose, dosing frequency, trough concentrations, drugs interact with posaconazole. Primary outcomes included the percentage of patients who achieved target trough levels of posaconazole. We also looked at factors correlated to trough concentrations, which included: dose, age, weight, presence of drug interactions and laboratory values such aspartate transaminase (AST), alanine transaminase (ALT), and albumin levels. Secondary outcomes included the correlation between posaconazole trough concentrations, clinical or microbiologic outcomes, and toxicity.
Results:
A total of 69 trough plasma concentrations were measured across 42 patients. Among these, 27 patients had a second trough level assessed. The mean concentration of the initial trough was 1.4 ± 1.3 mg/L (mean ± SD), with concentrations ranging from 0.2 to 6.2 mg/L. The mean concentration of the second trough was 0.99 ± 0.8 mg/L, ranging from 0.2 to 4.1 mg/L. For the initial trough concentrations, 59.5% fell within the therapeutic range. A total of 10 patients (23.8%) experienced adverse events that were attributed to posaconazole.
Conclusion:
Posaconazole trough concentrations vary in pediatric patients and around half of the patients achieved therapeutic concentrations with initial doses with minimal adverse events reported.
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