Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients

ABSTRACT This study aimed to investigate the dose and trough concentration ( C min ) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma C min s, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 C min s of 113 pediatric patients were detected. The median C min s were 1.0 and 1.3 mg/L for tablets and injections, respectively ( P < 0.05). The median doses required to achieve the target C min were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications ( P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect C min s of tablets, while age, gender, and BMI were found to be correlated with C min s of injections. IFD breakthrough occurred in 9.2% of patients with a median C min s of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median C min s of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring. This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.