DOI: 10.1097/inf.0000000000005347 ISSN: 0891-3668

Optimizing Posaconazole Suspension Prophylaxis in Pediatric Patients: The Key Role of Therapeutic Drug Monitoring

Maria Álvarez de Toledo, Maria Blanca Guembe Zabaleta, Laura Barenblit-Mas, María Larrosa-García, Aurora Fernandez-Polo, Laura Castellote, Laura Roig-Soria, Berta Renedo Miró, Maria Teresa Martín Gómez, Laura Alonso García, Sonia Garcia-Garcia, Natalia Mendoza-Palomar, Pere Soler-Palacin
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Background:

Posaconazole suspension is widely used for the prophylaxis of breakthrough invasive fungal infections in high-risk children. Due to its low bioavailability and high pharmacokinetic variability, therapeutic drug monitoring (TDM) is recommended.

Objectives:

To describe prophylactic posaconazole suspension TDM in children, evaluate its effectiveness and investigate factors influencing its pharmacokinetics.

Methods:

Retrospective observational study from 2017–2023, including consecutive patients <18 years receiving prophylaxis with posaconazole suspension for ≥1 week and with ≥1 posaconazole serum concentration (trough concentration [C trough ]).

Results:

Seventy-one patients were included (median age 4.8 [interquartile range, IQR 2.4–8.9] years). The most frequent underlying condition was inborn errors of immunity (23, 32.4%); 55 patients (77.5%) had undergone hematopoietic stem-cell transplantation. Out of 373 C trough , 178 (47.7%) were within the therapeutic range and 187 (50.1%) were subtherapeutic. The median posaconazole dose was significantly higher in patients under 2 (17.4 [IQR 12.6–23.7] mg/kg/day vs. 13.4 [IQR 12.0–18.4] mg/kg/day, P < 0.001). Nausea/vomiting (odds ratio [OR] 4.89; 95% confidence interval 2.09–11.44; P = 0.0003) and concomitant proton pump inhibitor use (OR 3.03; 95% confidence interval 1.15–7.95; P = 0.0248) were significantly associated with subtherapeutic C trough . Proven breakthrough invasive fungal infections occurred in 3 (4.2%) patients, with no statistically significant difference in subtherapeutic C trough values compared with the rest of the cohort ( P = 0.128). Toxicity was not related to supratherapeutic C trough .

Conclusions:

Our study highlights the importance of TDM in pediatric patients receiving posaconazole suspension, particularly those with risk factors associated with subtherapeutic C trough . Although further studies are needed to define the optimal dosage in children under 2, our findings suggest that these patients should receive at least 15 mg/kg/day.

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