(863) Ganciclovir Therapeutic Drug Monitoring in Critically Ill Pediatric Patients

Introduction: Commonly used drug references provide ganciclovir dose recommendations that may lead to subtherapeutic drug concentrations and risk of treatment failure in children with and without kidney dysfunction. Therapeutic drug monitoring (TDM) has been proposed to overcome this, with target 24-hour area under the curve (AUC24h) of 80-120 mg·h/L proposed for treatment of Cytomegalovirus infection. Limited data, however, are available regarding ganciclovir dosing and level attainment in critically ill children with and without renal insufficiency. The goal of this study was to evaluate ganciclovir dosing and pharmacokinetics (PK) in critically ill pediatric patients.

Methods: This retrospective, single-center, cohort study reviewed electronic medical records of patients ≤17 years of age who received ganciclovir with level monitoring in the pediatric intensive care unit (PICU) between July 2022 and July 2023. Data included ganciclovir dose, PK parameters, and continuous renal replacement therapy (CRRT) utilized.

Results: A total of 6 patients (median age 6.4 years; IQR 2.8-12.2) received ganciclovir in the PICU, with a total of 20 AUC24h values obtained. Nine AUC24h values were calculated for 3 patients who received continuous venovenous hemodiafiltration (CVVHDF; median clearance 2071 mL/1.73m2/hr; IQR 1965-2117). The median dose and frequency at time of first AUC24h was 2.5 mg/kg (IQR 2.5-4.4) and every 12 hours, respectively, with only one patient attaining goal AUC24h with initial dosing. Two doses were increased after the first AUC24h with no further levels. Three patients attained goal AUC24h after subsequent dose adjustments. Two of these patients were receiving CVVHDF, with 1.3 mg/kg every 24 hours and 2.5 mg/mg every 12 hours required, varying from the recommended dose of 2.5 mg/kg every 24 hours for CRRT. The remaining patient required ganciclovir 15 mg/kg every 6 hours, along with the addition of probenecid, to reach goal AUC24h. This dose was significantly higher than ganciclovir 5 mg/kg every 12 hours recommended with normal renal function.

Conclusions: Ganciclovir dosing necessary to attain goal PK parameters in critically ill pediatric patients varies from commonly recommended doses. Further study is needed to determine appropriate ganciclovir dosing and TDM in this population.