Can digoxin and amiodarone be used concomitantly?

From the Guidelines

Digoxin and amiodarone can be used together, but this combination requires careful monitoring and typically dose adjustment. When prescribing both medications, the digoxin dose should usually be reduced by approximately 50% because amiodarone increases digoxin blood levels by inhibiting P-glycoprotein, which normally helps eliminate digoxin from the body 1. This interaction can lead to digoxin toxicity if doses aren't adjusted appropriately. Patients on this combination should be monitored closely for signs of digoxin toxicity including nausea, vomiting, visual disturbances, confusion, and cardiac arrhythmias.

Key Considerations

• Regular monitoring of digoxin serum levels is essential, aiming to maintain therapeutic levels between 0.5-0.9 ng/mL for most indications 1.
• Additionally, electrolytes, particularly potassium, magnesium, and calcium, should be monitored as imbalances can increase the risk of adverse effects.
• Both medications can prolong the QT interval, so baseline and follow-up ECGs are important to assess for potential additive effects on cardiac conduction.

Monitoring and Dose Adjustment

• The concomitant use of amiodarone can increase serum digoxin concentrations and may increase the likelihood of digoxin toxicity 1.
• A low lean body mass and impaired renal function can also elevate serum digoxin levels, which may explain the increased risk of digoxin toxicity in elderly patients 1.
• The dose of digoxin should be reduced if treatment with these drugs is initiated, and patients should be closely monitored for signs of toxicity.

From the FDA Drug Label

In patients receiving digoxin therapy, administration of oral amiodarone regularly results in an increase in serum digoxin concentration that may reach toxic levels with resultant clinical toxicity Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On administration of oral amiodarone, the need for digitalis therapy should be reviewed and the dose reduced by approximately 50% or discontinued. If digitalis treatment is continued, serum levels should be closely monitored and patients observed for clinical evidence of toxicity

Key Considerations:

• The combination of digoxin and amiodarone can increase the risk of digitalis toxicity due to elevated serum digoxin concentrations.
• The dose of digoxin should be reduced by approximately 50% when administered concomitantly with amiodarone.
• Close monitoring of serum digoxin levels and observation for clinical evidence of toxicity are necessary when using these drugs together 2.

From the Research

Combination Therapy of Digoxin and Amiodarone

• The combination of digoxin and amiodarone has been associated with increased all-cause mortality in patients with atrial fibrillation, as shown in a study published in 2020 3.
• A population pharmacokinetic analysis found that the combination of digoxin and amiodarone affects digoxin pharmacokinetics, and the optimal dose of digoxin should be adjusted based on renal function and N-desethylamiodarone concentration 4.
• The interaction between digoxin and amiodarone is multifactorial, and close monitoring of serum digoxin levels and clinical features is necessary during concurrent therapy 5.

Clinical Significance and Therapeutic Implications

• The use of digoxin in combination with amiodarone requires careful consideration of the potential risks and benefits, particularly in patients with atrial fibrillation and heart failure 3, 4.
• Digoxin may be effective in the treatment of heart failure due to systolic dysfunction, but its use should be individualized and monitored closely, especially in elderly patients 6.
• The pharmacology and toxicology of digoxin highlight the importance of careful dosing and monitoring to avoid toxicity, which can have serious cardiotoxic effects 7.

Key Considerations for Combination Therapy

• Patients receiving combination therapy with digoxin and amiodarone should be closely monitored for signs of toxicity and adverse effects 5, 6.
• The dose of digoxin may need to be adjusted based on renal function, N-desethylamiodarone concentration, and other factors to minimize the risk of toxicity 4.
• Alternative therapies, such as beta-blockers or calcium antagonists, may be considered in patients with atrial fibrillation who are not responding to digoxin monotherapy 6.