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

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 [Ctrough]). 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 Ctrough, 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 Ctrough. Proven breakthrough invasive fungal infections occurred in 3 (4.2%) patients, with no statistically significant difference in subtherapeutic Ctrough values compared with the rest of the cohort (P = 0.128). Toxicity was not related to supratherapeutic Ctrough. CONCLUSIONS: Our study highlights the importance of TDM in pediatric patients receiving posaconazole suspension, particularly those with risk factors associated with subtherapeutic Ctrough. 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.