Drug Interactions Newsletter

Volume 1, Issue 16, 05/05/2009

Question

Part 1: What is the mechanism by which digoxin (Digitek®; Lanoxin®) concentrations are significantly increased with the use of amiodarone (Cordarone®)?

Answer

This is part 1 of a 2 part series.  The use of the cardiac glycoside, digoxin (Digitek®; Lanoxin®) is common in the treatment of symptomatic heart failure (HF) as well as in patients with atrial arrhythmias in need ventricular rate control.(1,2)  While digoxin therapy does offer a number of therapeutic benefits, unfortunately, it has not been proven to reduce mortality in patients with HF.  In addition, it is a narrow therapeutic index medication and thus requires monitoring of serum concentrations to avoid toxicity.   In regard to digoxin use for arrhythmias, some patients will require antiarrhythmic treatment for ventricular arrhythmias in addition to the rate control offered by digoxin; the well known antiarrhythmic medication, amiodarone (Cordarone®), is frequently used in these scenarios.(2,3)  This is an example of a handful of patient populations with multiple cardiovascular problems that are candidates for and often receive treatment with both digoxin and amiodarone.  Unfortunately, there is a clinically relevant drug interaction between the two, wherein amiodarone increases the concentration of digoxin.  If ignored, the patient is at increased risk for digoxin toxicity.(4-8)   What is the mechanism by which amiodarone increases digoxin concentrations?

There are two figures in this issue that diagram the mechanism for this drug interaction.  Other keywords found in this issue:  desethylamiodarone, P-gp, P-glycoprotein, CYP3A4, CYP2C8, cytochrome P450, enterocyte, renal tubular cell, kidney, gastrointestinal tract, GI, bioavailability, dose reductions

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