Interaction between digoxin and calcium antagonists and antiarrhythmic drugs

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Abstract
The influence of several Ca antagonists and antiarrhythmic drugs on digoxin kinetics and actions were investigated in 36 healthy men during digoxin steady state (0.375 mg/day). The subjects were randomly assigned to 3 subgroups and each group received placebo (control) and 2 of the following regimens (doses 3 times/day) in a randomized sequence for 2 wk each: verapamil (80 mg) and nifedipine (10 mg), verapamil (120 mg) and gallopamil (50 mg), or propafenone (150 mg) and quinidine (250 mg). Plasma digoxin concentration (PDC) rose during the cotreatments in the sequence: gallopamil (+16%) < propafenone (+37%) < nifedipine (+45%) < verapamil (almost independent of dose, +69%) < quinidine (+118%). These increases in PDC correlated closely to decreases in renal digoxin clearances. Renal creatinine clearance was virtually unaffected. The rise of PDC resulted in increased glycoside effects, as measured by the shortening of systolic time intervals and flattening of T wave. There was a linear correlation between PDC and changes in mean corrected electromechanical systole and T wave flattening. Evidently, in addition to quinidine, other antiarrhythmic drugs and various Ca antagonists interact kinetically with digoxin and the increasing PDC is cardioactive.

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