Digoxin toxicity developed in 4 patients when they were given ciclosporin before cardiac transplantation. In two cases described in detail, ciclosporin 10 mg/kg daily was added to digoxin 375 micrograms daily. Fourfold rises in digoxin levels,from 1.2 to 4.5 nanograms/mL and from 2 to 8.3 nanograms/mL,were seen within 2 to 3 days. This was accompanied by rises in serum creatinine levels from 110 to 120 micromol/L and from 84 to 181 micromol/L respectively, which were considered insufficient to explain rise in digoxin levels. As a consequence of these findings, same authors conducted a study in 4 patients given ciclosporin and digoxin. Two patients developed acute renal failure. In other 2 patients, volume of distribution of digoxin was decreased by 69 % and 72%, while clearance was reduced by 47 % and 58 % (See reference number 1). In a further 7 patients,digoxin pharmacokinetics were assessed before cardiac transplantation, then after transplantation during maintenance ciclosporin therapy (See reference number 2). The total body clearance of digoxin remained unchanged, which appeared to be at odds with earlier results (See reference number 1). It was suggested that haemodynamic improvements brought about by successful cardiac transplantation may have counterbalanced any inhibitory effect ciclosporin had on renal clearance (See reference number 2).
Not fully understood. The authors of studies concluded that ciclosporin has no specific inhibitory effect on renal elimination of digoxin, but that it causes a non-specific reduction in renal function after acute administration, which reduces digoxin elimination (See reference number 2). Conversely, another study in animals suggested that ciclosporin can reduce secretion of digoxin by kidney tubular cells by inhibiting P-glycoprotein (See reference number 3).
Information seems limited to studies cited. Nevertheless, effects of concurrent use should be monitored very closely, and digoxin dosage should be adjusted as necessary.
1. Dorian P,Cardella C, Strauss M, David T, East S, Ogilvie R. Cyclosporine nephrotoxicity andcyclosporine-digoxin interaction prior to heart transplantation. Transplant Proc (1987) 19, 1825–7.
Robieux I,Dorian P, Klein J, Chung D, Zborowska-Sluis D, Ogilvie R, Koren G. The effectsof cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics. J Clin Pharmacol (1992) 32, 338–43.
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