Can Amiodarone be administered with digoxin (Digitalis glycoside)?

Can Amiodarone Be Given With Digoxin?

Yes, amiodarone can be administered with digoxin, but the digoxin dose must be reduced by 50% when amiodarone is initiated, and plasma digoxin levels require close monitoring to prevent toxicity. 1

Mechanism of Drug Interaction

The interaction between these medications is clinically significant and predictable:

• Digoxin levels consistently double after coadministration with amiodarone due to inhibition of digoxin secretion from renal tubules and P-glycoprotein membrane transporter system blockade 1, 2
• Amiodarone reduces total body clearance of digoxin by approximately 29% and nonrenal clearance by 33% 3
• The elimination half-life of digoxin is prolonged by approximately 31% when combined with amiodarone 3

Required Dose Adjustments

When initiating amiodarone in patients already taking digoxin:

• Reduce digoxin dose by 50% immediately when amiodarone is started 1, 2
• For IV digoxin loading during amiodarone infusion, reduce the standard loading dose by 30-50% to approximately 0.125-0.35 mg IV bolus 4
• For maintenance therapy, reduce the standard maintenance dose by 30-50% based on the patient's age, weight, and renal function 4, 2

Special considerations for Japanese patients with atrial fibrillation and heart failure:

• For patients with creatinine clearance >30 mL/min taking amiodarone: use digoxin 0.0625 mg daily 5
• For patients with creatinine clearance ≤30 mL/min and N-desethylamiodarone concentration >600 ng/mL: use digoxin 0.03125 mg daily 5

Mandatory Monitoring Protocol

Baseline assessment before combining medications:

• Obtain baseline digoxin level before starting amiodarone 1
• Check renal function (creatinine clearance) as this significantly affects digoxin clearance 4, 5

Ongoing monitoring requirements:

• Check digoxin levels at baseline, during loading phase, and every 6 months during maintenance therapy 1
• Monitor more frequently when initiating or adjusting amiodarone therapy 4
• Target trough serum digoxin level: 0.5-1.0 ng/mL (levels >2 ng/mL are associated with toxicity, though symptoms may occur at lower levels) 1, 4
• Monitor for signs of digoxin toxicity including gastrointestinal symptoms (nausea, vomiting), neurological symptoms (confusion, visual disturbances), and cardiac arrhythmias 4, 3

Clinical Toxicity Risk

The combination carries substantial risk if not properly managed:

• In one study of 28 patients, gastrointestinal side effects occurred in 9 patients (32%), central nervous system reactions in 5 patients (18%), and cardiovascular reactions in 4 patients (14%) when amiodarone was added to digoxin therapy 3
• Digoxin toxicity commonly occurs with serum levels >2 ng/mL but may occur at lower levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist 6

Absolute Contraindications and Precautions

Do not use this combination in patients with:

• Second or third-degree heart block without a pacemaker 1, 4
• Significant sinus or atrioventricular block unless treated with a permanent pacemaker 6
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 1, 4

Use with extreme caution in:

• Renal dysfunction (requires further dose reduction) 1, 4, 5
• Pre-existing AV block or SA node dysfunction 1, 4
• Patients receiving other drugs with SA and/or AV nodal-blocking properties 1

Common Pitfalls to Avoid

• Never continue full-dose digoxin when starting amiodarone - this predictably leads to toxic digoxin levels 1
• Do not assume the interaction is immediate; amiodarone has a long half-life, so interactions can develop gradually and persist after discontinuation 2
• Avoid grapefruit juice in patients taking amiodarone, as it increases amiodarone levels by 50% and can indirectly worsen the digoxin interaction 1, 2
• Remember that N-desethylamiodarone (the active metabolite) contributes significantly to the interaction, particularly in reducing digoxin clearance 5