Amiodarone Interaction Time Differences with Warfarin and Digoxin

Abstract

Background:

Amiodarone has pharmacokinetic and pharmacodynamic interactions with various therapeutic agents. The mechanism of interaction between warfarin and amiodarone is the inhibition of warfarin metabolism by amiodarone, and that between digoxin and amiodarone is the inhibition of digoxin transport by amiodarone.

Objective:

To investigate the pharmacokinetic magnitude of the time differences between amiodarone–warfarin and amiodarone–digoxin interactions.

Methods:

Amiodarone was administered concomitantly to 79 inpatients who had been receiving fixed-maintenance doses of warfarin or digoxin. Seventy-seven inpatients were prescribed warfarin therapy, and 54 inpatients were prescribed digoxin therapy. To determine serum concentrations of the warfarin enantiomers digoxin, amiodarone, and desethylamiodarone blood samples were obtained with coadministration of amiodarone. Serum S- and R-warfarin, amiodarone, and desethylamiodarone concentrations were measured by HPLC methods, and serum digoxin concentrations were measured by a fluorescence polarization immunoassay.

Results:

A remarkable decrease of S-warfarin clearance was observed within approximately the first 2 weeks after coadministration of amiodarone. Only a small decrease in R-warfarin clearance was observed. Digoxin clearance was gradually decreased with time, and a good reverse correlation was obtained between amiodarone or desethylamiodarone concentrations and digoxin clearance.

Conclusions:

Relatively short-term monitoring of warfarin clearance is required when amiodarone is coadministered. Long-term monitoring of digoxin serum amiodarone and desethylamiodarone concentrations is necessary to detect the amiodarone–digoxin interaction.