Digoxin toxicity in childhood: Emphasis on recent advances

Digoxin is the most widely used agent in the treatment of congestive heart failure in childhood, but despite improved knowledge of digoxin pharmacodynamics and kinetics, digoxin-induced arrhythmias have remained a major problem. In this paper, we emphasize age-dependent factors of digoxin kinetics in neonates and young children, which distinguish them from adults, and the different types of arrythmias which are seen in different age groups. Comparisons with animal models are made and an explanation is offered for these age-dependent patterns of arrhythmias. In addition, recent advances and studies of the interactions of digoxin with various drugs, such as the anti-arrhythmics quinidine, verapamil and amiodarone, and other agents, such as indomethacin and various antibiotics, are reviewed in both human and animal models. Recent advances in the treatment of severe toxicity, such as the use of digoxin-specific Fab antibody fragments, are described. Finally, dosage recommendations for digoxin in premature and full-term neonates, young children and adolescents are presented, based upon well-accepted pharmacological principles.