Digoxin toxicity associated with amiodarone therapy in children

Area of Science:

• Pharmacology
• Pediatric Cardiology

Background:

• Digoxin is a cardiac glycoside used to treat heart failure and arrhythmias.
• Amiodarone is an antiarrhythmic drug with a complex pharmacologic profile.

Observation:

• In nine pediatric patients, co-administration of amiodarone with digoxin resulted in a marked rise in serum digoxin concentrations (68%–800%).
• This increase occurred despite stable serum creatinine and blood urea nitrogen (BUN) levels.

Findings:

• Amiodarone prolonged the half-life of digoxin.
• The digoxin accumulation was attributed to reduced renal clearance via inhibited tubular secretion and a decreased volume of distribution.
• Creatinine clearance remained unaffected by amiodarone.

Implications:

• The drug interaction between amiodarone and digoxin is more pronounced in children due to their greater reliance on renal tubular secretion for digoxin clearance.
• Close monitoring of serum digoxin concentrations and potential dose adjustments are essential when initiating concurrent therapy in pediatric patients.
• This interaction highlights the importance of understanding drug pharmacokinetics in pediatric populations to ensure safe and effective treatment.