Summary

Amiodarone significantly increases digoxin plasma concentrations by inhibiting P-glycoprotein transport and reducing renal clearance. This interaction can lead to digoxin toxicity and requires careful dose adjustment and monitoring when these medications are used together.

Introduction

Amiodarone is a class III antiarrhythmic medication primarily used to treat life-threatening ventricular arrhythmias and atrial fibrillation. It works by blocking potassium channels and has additional effects on sodium and calcium channels. Digoxin is a cardiac glycoside derived from the foxglove plant, commonly prescribed for heart failure and atrial fibrillation to improve cardiac contractility and control heart rate. Both medications are frequently used in cardiovascular medicine, making their potential interaction clinically significant.

Mechanism of Interaction

The interaction between amiodarone and digoxin occurs through multiple mechanisms. Amiodarone inhibits P-glycoprotein, a transport protein responsible for digoxin efflux from cells and elimination through the kidneys and intestines. This inhibition reduces digoxin clearance and increases its bioavailability. Additionally, amiodarone may compete with digoxin for renal tubular secretion, further decreasing digoxin elimination. The interaction typically develops gradually over 1-2 weeks as amiodarone reaches steady-state concentrations, and can increase digoxin levels by 70-100%.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity, which can manifest as cardiac arrhythmias, including bradycardia, heart block, and potentially fatal ventricular arrhythmias. Non-cardiac symptoms of digoxin toxicity include nausea, vomiting, visual disturbances (yellow-green halos), confusion, and fatigue. The interaction is particularly concerning because both drugs have narrow therapeutic windows and are used in patients with underlying cardiac conditions. Elderly patients and those with renal impairment are at higher risk for developing toxicity due to reduced drug clearance.

Management and Precautions

When amiodarone is initiated in patients taking digoxin, the digoxin dose should be reduced by approximately 50% and serum digoxin levels monitored closely. Digoxin levels should be checked within 1-2 weeks of starting amiodarone and periodically thereafter. Target digoxin levels should be maintained at the lower end of the therapeutic range (0.8-1.2 ng/mL). Patients should be monitored for signs and symptoms of digoxin toxicity, including ECG changes, heart rate, and clinical symptoms. If amiodarone is discontinued, digoxin levels may decrease over several weeks to months due to amiodarone's long half-life, potentially requiring digoxin dose adjustments.

Amiodarone interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided as they can significantly increase amiodarone blood levels and risk of toxicity. Alcohol consumption should be limited or avoided as it may increase the risk of liver toxicity when combined with amiodarone. Patients should maintain consistent dietary habits and avoid excessive sun exposure, as amiodarone can cause photosensitivity reactions and skin discoloration with prolonged sun exposure.

Digoxin interactions with food and lifestyle

Digoxin has several important food and lifestyle interactions that patients should be aware of. High-fiber foods, including bran cereals and fiber supplements, can significantly reduce digoxin absorption and should be taken at least 2 hours apart from digoxin doses. St. John's wort, an herbal supplement, can decrease digoxin levels and reduce its effectiveness, so concurrent use should be avoided. Alcohol consumption can affect digoxin levels and increase the risk of side effects, particularly heart rhythm abnormalities. Patients should limit alcohol intake and discuss any alcohol use with their healthcare provider. Additionally, maintaining consistent dietary habits is important, as sudden changes in fiber intake or meal timing can affect digoxin absorption and blood levels. Patients should also be cautious with salt substitutes containing potassium, as changes in potassium levels can affect digoxin's effectiveness and safety.