What is the recommended dose of digoxin (digitalis glycoside) for adults with atrial fibrillation or heart failure?

Digoxin Dosing for Adults with Atrial Fibrillation or Heart Failure

For most adults with normal renal function, initiate digoxin at 0.25 mg once daily; reduce to 0.125 mg daily for patients over 70 years, those with impaired renal function (GFR <60 mL/min), or low lean body mass, and further reduce to 0.0625 mg daily for marked renal impairment (GFR 15-30 mL/min). 1, 2

Standard Maintenance Dosing Algorithm

For patients under 70 years with normal renal function:

• Start with 0.25 mg once daily 3, 2, 4
• Target serum concentration: 0.5-0.9 ng/mL 1

For patients over 70 years OR with impaired renal function:

• Start with 0.125 mg once daily 3, 1, 2
• This lower dose prevents toxicity in elderly patients who have prolonged digoxin half-life (69.6 vs 36.8 hours in younger patients) 5

For patients with marked renal impairment (GFR <30 mL/min):

• Start with 0.0625 mg once daily 3, 1
• Consider every-other-day dosing in severe renal impairment 1
• Critical caveat: Patients with GFR <15 mL/min should avoid digoxin unless absolutely necessary with extremely close monitoring 6

Loading Dose Strategy (When Rapid Digitalization Needed)

For acute atrial fibrillation with rapid ventricular rate:

• Initial IV bolus: 0.25-0.5 mg over 10 minutes 3
• Additional 0.25 mg doses at 6-8 hour intervals 3
• Maximum total loading dose: 1.0 mg over 24 hours (8-12 mcg/kg) 3, 2
• Important limitation: Loading doses are NOT recommended for chronic heart failure patients in sinus rhythm 4

Common pitfall: A case series found that 26 hospitalized patients who received loading doses for rapid AF developed toxicity when they had impaired renal function, despite following standard nomograms 7. Always reduce loading doses by 50% in renal impairment 8.

Target Serum Concentrations

Therapeutic range: 0.5-0.9 ng/mL for heart failure 1

• Concentrations >1.0 ng/mL provide no additional benefit and increase mortality risk 1
• The DIG trial achieved mean concentrations of 0.97-1.01 ng/mL 2

For atrial fibrillation rate control:

• Target range: 0.6-1.2 ng/mL 3
• However, digoxin alone is often inadequate for rate control during exercise 3

Toxicity threshold:

• Commonly occurs at levels >2 ng/mL 3, 4
• Can occur at lower levels with hypokalemia, hypomagnesemia, or hypothyroidism 3, 4

Dose Adjustments for Drug Interactions

When adding amiodarone:

• Reduce digoxin dose by 30-50% 3, 9, 4
• Check digoxin levels more frequently 9
• Amiodarone inhibits P-glycoprotein, reducing digoxin clearance 9

When adding dronedarone:

• Reduce digoxin dose by at least 50% 3, 1

When adding verapamil:

• Monitor digoxin levels closely 3
• Verapamil inhibits P-glycoprotein 3

Other interacting medications requiring monitoring:

• Clarithromycin, erythromycin, itraconazole, posaconazole, voriconazole, cyclosporine, propafenone, quinidine, flecainide 3, 4

Maximum Recommended Doses

The maximum daily maintenance dose is 0.375 mg, though doses this high are rarely needed or appropriate 1

• Most patients require only 0.125-0.25 mg daily 1
• Higher doses (0.375-0.5 mg daily) are rarely necessary and increase toxicity risk 4
• If rate control remains inadequate at 0.25 mg daily, add a beta-blocker or calcium channel blocker rather than increasing digoxin further 1

Clinical Indications and Patient Selection

Heart failure with reduced ejection fraction (HFrEF):

• Use in patients with LVEF <40% and NYHA class II-IV symptoms 3, 1, 4
• Consider for persistent symptoms despite guideline-directed medical therapy 1
• Reduces hospitalization but does not improve mortality 3, 4

Atrial fibrillation:

• Most appropriate for patients with concurrent heart failure 1
• Useful for sedentary patients or those who cannot tolerate beta-blockers 5
• Combination therapy is superior: Digoxin plus beta-blocker is more effective than digoxin alone, particularly during exercise 1

Absolute Contraindications

Do not use digoxin in:

• Second or third-degree AV block without permanent pacemaker 3, 4
• Pre-excitation syndromes (WPW with AF/atrial flutter) 3
• Previous digoxin intolerance 3

Monitoring Requirements

Timing of serum sampling:

• Draw levels just before next scheduled dose 2
• If not possible, wait at least 6-8 hours after last dose 2
• On once-daily dosing, concentrations are 10-25% lower at 24 vs 8 hours 2

Frequency of monitoring:

• Check early during therapy in patients with renal impairment 3, 6
• Steady-state achieved in 5 half-lives (1-3 weeks depending on renal function) 2
• More frequent monitoring when initiating interacting medications 9

Essential laboratory monitoring:

• Serum potassium and magnesium (hypokalemia/hypomagnesemia increase toxicity risk) 3, 6, 4
• Renal function (creatinine clearance) 3, 6
• The deindexed eGFR by MDRD equation has the highest correlation with digoxin trough concentrations 10

Signs of Digoxin Toxicity

Cardiac manifestations:

• Bradycardia, AV block, atrial and ventricular arrhythmias 3

Gastrointestinal symptoms:

• Anorexia, nausea, vomiting 3, 1

Neurological symptoms:

• Confusion, visual disturbances (color vision changes), disorientation 3, 1

Management of toxicity:

• Consider digoxin-specific Fab antibody fragments for ventricular arrhythmias 3

Special Clinical Scenarios

Hypotension limiting beta-blocker use:

• Digoxin does not lower blood pressure, making it particularly useful when hypotension limits other rate-control agents 1
• Consider ultra-low-dose digoxin (0.0625 mg) combined with very low-dose beta-blocker 1

Advanced CKD (GFR 15-30 mL/min):

• Start with 0.0625 mg daily or every other day 1, 6
• Reduce dose by 50-75% from standard dosing 6
• Target concentration: 0.5-0.9 ng/mL 1