Digoxin-cyclosporine interaction: severe digitalis toxicity after cyclosporine treatment

Digoxin toxicity developed in two patients awaiting cardiac transplantation upon the initiation of cyclosporine. Toxicity was associated with elevated digoxin concentrations (10.6 and 5.7 nmoles/L), gastrointestinal symptoms, and arrhythmias classic for digoxin toxicity (bidirectional ventricular tachycardia and AV nodal block with accelerated junctional rhythm respectively). A previously unreported drug interaction between cyclosporine and digoxin was suspected and digoxin pharmacokinetics were studied in two additional patients both before and after cyclosporine therapy prior to cardiac transplantation. The study confirmed a significant interaction between cyclosporine and digoxin; the apparent volume of distribution of digoxin decreased by 71% and its plasma clearance decreased by 53%. Until further information regarding the cyclosporine-digoxin interaction is available, this combination should be used with great caution.