Evaluation of Sirolimus Dosing in Neonates and Infants With Lymphatic Disorders: A Case Series.

OBJECTIVE

Literature in pediatric patients suggests dosing sirolimus 1.6 mg/m2/day divided twice daily for lymphatic disorders with limited evidence available for dosing in neonates and infants. The objective of this research was to determine the sirolimus dose required to achieve therapeutic trough concentrations in infants with lymphatic disorders at Children's Hospital of Philadelphia.

METHODS

This retrospective review included patients <1 year of age at Children's Hospital of Philadelphia who were initiated on sirolimus for lymphatic disorder. Patients were included if they received at least 5 days of consecutive sirolimus therapy prior to trough concentration monitoring. Measures of central tendency and variability were used for statistical analysis.

RESULTS

A total of 16 patients met criteria for inclusion. The median initial sirolimus dose was 1 mg/m/day (IQR, 0.5-1.6 mg/m/day). Fourteen patients (87.5%) achieved therapeutic trough concentrations on a median sirolimus dose of 0.5 mg/m/day. Dosing frequency to achieve therapeutic trough concentrations included 1 patient (6.25%) on twice daily dosing, 12 patients (75%) on once daily dosing, and 1 patient (6.25%) requiring every 48-hour dosing. The median time to first therapeutic trough was 15.5 days (IQR, 5.5-18.5 days), and patients required a median of 1 dose adjustment.

CONCLUSIONS

A median sirolimus dose to achieve therapeutic sirolimus trough concentrations in infants with lymphatic disorders was 0.5 mg/m/day with a median of 1 dose adjustment. Sirolimus was well tolerated in the study population.