Supratherapeutic Digoxin Levels in Children with Cardiac Disease

We characterized our institution's experience with supratherapeutic digoxin levels (> 2.0 mcg/L) which is reported to occur in 0.8-4% of treated patients. Children < 18 years with a measured digoxin level between January 2014 and December 2024 were included. Data were obtained from the electronic health record including digoxin dose, indication, renal function, and clinical interventions. Descriptive patient-level analyses were performed in children with supratherapeutic levels. Laboratory sample-level analyses were performed using all measured digoxin levels comparing high (> 2.0mcg/L) verses low accounting for repeated measurements within patients. Multivariable models report adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Overall, 604 digoxin levels were obtained in 283 patients, of which 63 levels (10.4%) were > 2.0 mcg/L in 42 (14.8%) patients. Among patients with elevated levels, median age was 16-months (interquartile range [IQR]: 4-37) and 42% had documented clinical symptoms. Digoxin indications included heart failure (38%), interstage management (38%), and arrhythmia (17%). Median elevated digoxin level was 2.5mcg/L (IQR: 2.2-3.1) and dose was 7.9 mcg/kg/day (IQR: 6.1-9.9). Most patients (76%) were on interacting medications, 25% had moderate/severe renal dysfunction and clinical interventions occurred in 93%. At the sample-level, independent associations with higher odds of supratherapeutic levels included renal dysfunction (severe aOR 6.1, 95%CI 1.4-26.2]; moderate 4.3 [1.2-15.6], mild 2.9 [1.0-8.0] versus normal) and higher daily dose (1.2 mg/kg [1.0-1.3]). Outpatient samples were associated with lower odds of supratherapeutic levels. Supratherapeutic digoxin levels were common, frequently prompting clinical intervention, and associated with renal dysfunction and higher doses, supporting closer monitoring and dose adjustment in high-risk patients.