What is the starting dose of digoxin (digitalis glycoside) for atrial fibrillation (AF)?

Digoxin Dosing for Atrial Fibrillation

For most adults with atrial fibrillation, start digoxin at 0.125-0.25 mg daily orally, but use the lower end of this range (0.0625-0.125 mg daily) for patients over 70 years, those with impaired renal function, or low lean body mass. 1, 2

Oral Maintenance Dosing Strategy

Standard dosing:

• Most adults with normal renal function: 0.125-0.25 mg daily 1, 2
• Patients >70 years: 0.125 mg daily or 0.0625 mg daily 2, 3
• Impaired renal function: 0.0625-0.125 mg daily 1, 2
• Low lean body mass: 0.0625-0.125 mg daily 2, 3

The 2016 ESC guidelines explicitly state that the long-term oral rate control dose range is 0.0625-0.25 mg daily, with the critical caveat that high plasma levels are associated with increased risk of death. 1 This mortality concern is substantiated by recent data showing patients with serum digoxin concentrations ≥1.2 ng/ml had a 56% increased hazard of mortality. 4

Acute IV Dosing (When Rapid Rate Control Needed)

For acute intravenous rate control in atrial fibrillation with rapid ventricular response:

• Initial IV bolus: 0.5 mg 1
• Total loading over 24 hours: 0.75-1.5 mg in divided doses 1
• Alternative regimen: 0.25-0.5 mg IV initially, then 0.25 mg at 6-8 hour intervals up to maximum 1.0 mg over 24 hours 2

Critical caveat: Beta-blockers provide superior acute heart rate control compared to digoxin monotherapy. 1 Digoxin is typically used in combination with beta-blockers rather than as monotherapy for AF rate control. 2

Target Serum Concentration and Monitoring

Maintain serum digoxin concentration between 0.5-0.9 ng/mL 2, 3

This lower target range is crucial because:

• Concentrations above 1.0 ng/mL have not shown superior outcomes and may increase mortality risk 2
• Each 0.5 ng/mL increase in serum concentration is associated with a 19% higher adjusted hazard of death 4
• The traditional "therapeutic range" of 0.6-1.2 ng/mL may be too high for optimal safety 5

Monitor:

• Renal function before starting and regularly thereafter 1
• Serum electrolytes (potassium, magnesium) 2
• Digoxin levels when adding interacting medications or if toxicity suspected 2

Dose Adjustments for Drug Interactions

Reduce digoxin dose by 30-50% when adding amiodarone 2, 3

Other medications requiring dose reduction and close monitoring include: 2, 3, 6

• Dronedarone (reduce by at least 50%)
• Verapamil
• Quinidine
• Clarithromycin/erythromycin
• Propafenone

Recent pharmacokinetic data shows that N-desethylamiodarone (amiodarone's metabolite) significantly reduces digoxin clearance, with a 3% decrease in clearance for every 100 ng/mL increase in N-desethylamiodarone concentration. 7 For patients on amiodarone with creatinine clearance ≤30 mL/min and N-desethylamiodarone >600 ng/mL, consider doses as low as 0.03125 mg daily. 7

Combination Therapy Approach

Digoxin should typically be combined with beta-blockers for optimal rate control in AF. 1, 2

The evidence hierarchy for rate control:

• Beta-blocker + digoxin is more effective than digoxin alone, particularly during exercise 2, 3
• Digoxin + diltiazem or verapamil is effective but less synergistic than beta-blocker combination 2
• Triple therapy may be required for adequate rate control, but monitor for excessive bradycardia 2

If rate control remains inadequate at 0.25 mg daily, add a beta-blocker or calcium channel blocker rather than increasing digoxin further. 2 The maximum recommended daily maintenance dose is 0.375 mg, though doses this high are rarely needed or appropriate. 2

Absolute Contraindications

Do not use digoxin in: 2, 3, 6

• Significant sinus or second/third-degree AV block without a permanent pacemaker
• Pre-excitation syndromes (WPW with AF/atrial flutter)
• Previous evidence of digoxin intolerance

Use With Caution In:

• Patients receiving other AV nodal-blocking agents (beta-blockers, calcium channel blockers, amiodarone) 6
• Hypokalemia, hypomagnesemia, or hypothyroidism (increases toxicity risk) 2, 6
• Hepatic dysfunction 2

Signs of Digoxin Toxicity

Monitor for: 2, 3, 6

• Cardiac: Arrhythmias (ectopic beats, heart block, bradycardia)
• Gastrointestinal: Anorexia, nausea, vomiting
• Neurological: Visual disturbances (yellow-green halos), confusion, disorientation, dizziness

Toxicity commonly occurs with serum levels >2 ng/mL but may occur at lower levels with electrolyte abnormalities. 6

Special Clinical Considerations

For patients with AF and concomitant heart failure: Digoxin is particularly appropriate as it does not lower blood pressure, making it useful when hypotension limits beta-blocker use. 2 However, digoxin reduces hospitalizations but has no mortality benefit in heart failure. 2

For paroxysmal AF: The same dosing principles apply (0.0625-0.25 mg daily), but recognize that beta-blockers and calcium channel blockers are generally more effective first-line options. 3 Digoxin does not effectively convert recent-onset AF to sinus rhythm—spontaneous conversion is common regardless of digoxin use. 8

Important limitation: Historical data shows that "therapeutic" serum levels of digoxin may fail to control ventricular rate in AF, especially in seriously ill patients with conditions like infection, hypoxia, or recent surgery. 9 This underscores why combination therapy is preferred.