Digoxin Dosing for Atrial Fibrillation
Standard Maintenance Dosing
For most adults under 70 years with normal renal function, start digoxin at 0.25 mg once daily; for patients ≥70 years, those with any renal impairment (CrCl <60 mL/min), or low lean body mass, use 0.125 mg daily or lower. 1, 2
Age-Based Dosing Algorithm
- Under 70 years + normal renal function (CrCl ≥60 mL/min): 0.25 mg daily 1, 2
- Age ≥70 years OR any renal impairment: 0.125 mg daily 1, 2
- Marked renal impairment (CrCl <30 mL/min): 0.0625 mg daily or every other day 1, 2
- Severe renal impairment (CrCl <15 mL/min): 0.0625 mg every other day; avoid if possible 1
Do not exceed 0.25 mg daily in the vast majority of patients—higher doses (0.375–0.5 mg) are rarely needed and increase mortality risk without improving outcomes. 1, 3
Target Serum Concentrations
Aim for 0.5–0.9 ng/mL for heart failure or 0.6–1.2 ng/mL for atrial fibrillation. 1, 4 Concentrations above 1.0 ng/mL offer no additional benefit and are associated with increased mortality in heart failure patients. 1
Loading Doses: When and How
Loading doses are generally NOT required for stable outpatients with atrial fibrillation—start maintenance dosing directly. 1, 5 Loading increases toxicity risk without improving long-term outcomes in chronic management. 1
When Loading Is Appropriate
Only consider IV loading for hemodynamically stable patients requiring urgent rate control in acute atrial fibrillation with rapid ventricular response. 5
IV Loading Protocol
- Initial bolus: 0.25–0.5 mg IV over ≥5 minutes 5
- Subsequent doses: 0.25 mg IV every 6–8 hours 5
- Maximum total: 1.0 mg over 24 hours (8–12 mcg/kg ideal body weight) 1
- Reduce loading dose by 50% in patients >70 years, renal impairment, low lean body mass, or concurrent amiodarone/verapamil/diltiazem 5
Critical caveat: Beta-blockers or calcium channel blockers (diltiazem, verapamil) are superior to digoxin for acute rate control and should be used first-line unless contraindicated (e.g., LVEF <40%, hypotension, heart failure). 5
Mandatory Pre-Treatment Assessment
Before initiating digoxin, obtain:
- Baseline ECG to exclude second- or third-degree AV block or pre-excitation syndromes (absolute contraindications) 1
- Renal function (serum creatinine and calculated CrCl using Cockcroft-Gault equation) 1
- Serum potassium (target 4.0–5.5 mEq/L) and magnesium—deficiencies markedly increase toxicity risk even at therapeutic digoxin levels 1
- Thyroid function if clinically indicated (hypothyroidism increases toxicity risk) 1
Dose Adjustments for Drug Interactions
Reduce digoxin dose by 30–50% when co-administered with:
- Amiodarone 1, 4
- Verapamil or diltiazem 1
- Clarithromycin or erythromycin (but NOT azithromycin—see below) 1
- Itraconazole, cyclosporine, propafenone, quinidine 1
Reduce dose by ≥50% with dronedarone. 1
Azithromycin Exception
Azithromycin can be safely prescribed with digoxin without dose adjustment in standard-risk patients—it does not produce the same P-glycoprotein inhibition as erythromycin or clarithromycin. 1 However, monitor for toxicity in high-risk patients (elderly, renal impairment, electrolyte abnormalities). 1
Monitoring Strategy
Timing of Serum Digoxin Levels
Draw levels at least 6–8 hours after the last dose to allow serum-tissue equilibration; earlier draws underestimate true steady-state concentration. 1, 4
When to Check Levels
- After starting interacting medications (amiodarone, verapamil, diltiazem, macrolides) 4
- When signs of toxicity appear (check immediately regardless of timing) 4
- With worsening renal function 4
- NOT routinely once stable dose established—no evidence that regular monitoring improves outcomes 4
Concurrent Laboratory Monitoring
- Serum potassium and magnesium at each follow-up visit 1
- Renal function regularly, especially in elderly patients 1
- Thyroid function if clinically indicated 4
Combination Therapy for Rate Control
Digoxin monotherapy is ineffective for rate control during exercise due to its vagally-mediated mechanism, which is overcome by sympathetic stimulation. 1, 6
Combine digoxin with a beta-blocker for optimal rate control at rest and during exercise—this combination is more effective than either agent alone. 1 The combination of digoxin plus diltiazem or verapamil is less synergistic but acceptable when beta-blockers are contraindicated. 1
Monitor for excessive bradycardia or AV block when combining digoxin with other AV nodal-blocking agents. 1
Absolute Contraindications
- Second- or third-degree AV block without a permanent pacemaker 1, 3
- Pre-excitation syndromes (Wolff-Parkinson-White) with atrial fibrillation—digoxin can shorten accessory pathway refractory period and precipitate ventricular fibrillation 1
- Previous documented digoxin intolerance 1
Relative Contraindications (Use With Extreme Caution)
- Decompensated heart failure with hypotension or cardiogenic shock 1
- Uncorrected hypokalemia, hypomagnesemia, or hypothyroidism 1, 3
- Acute myocardial infarction 1
- Severe renal impairment (CrCl <15 mL/min) 1
Recognizing Digoxin Toxicity
Toxicity can occur at serum levels <2 ng/mL when precipitating factors are present (hypokalemia, hypomagnesemia, hypothyroidism, renal dysfunction, drug interactions). 1, 3
Clinical Manifestations
Cardiac: Ventricular ectopy, AV block, bradycardia, bidirectional ventricular tachycardia 1
Gastrointestinal (often earliest signs): Anorexia, nausea, vomiting 1, 3
Neurological: Visual disturbances (yellow-tinted or blurred vision), confusion, disorientation 1, 3
Special Clinical Scenarios
Atrial Fibrillation with Heart Failure (LVEF <40%)
Digoxin is particularly useful in this population—it provides both rate control and a 28% reduction in heart failure hospitalizations without lowering blood pressure. 1 This makes it ideal when hypotension limits beta-blocker use. 1
Elderly Patients (≥75 Years)
Never exceed 0.125 mg daily in patients ≥75 years, even with normal renal function—higher doses are associated with increased toxicity. 1 Consider 0.0625 mg daily or every-other-day dosing in very elderly patients with multiple risk factors. 1
Advanced Renal Impairment (e.g., CrCl 17 mL/min)
For a patient with CrCl 17 mL/min, start 0.0625 mg every other day and monitor closely. 1 Steady-state will take longer to achieve (potentially 2–3 weeks). 4 Check digoxin level 1–2 weeks after initiation, targeting 0.5–0.9 ng/mL. 1
Common Pitfalls to Avoid
- Using 0.25 mg daily in elderly patients or those with any renal impairment—this is the most common dosing error leading to toxicity 1, 7
- Failing to reduce dose when adding amiodarone—proactively reduce digoxin by 50% rather than waiting for toxicity 4
- Drawing digoxin levels <6 hours post-dose—this underestimates true steady-state concentration 1, 4
- Ignoring electrolyte abnormalities—hypokalemia and hypomagnesemia potentiate toxicity even at therapeutic digoxin levels 1, 3
- Using digoxin monotherapy for rate control in active patients—combine with beta-blocker for exercise tolerance 1, 6
- Initiating loading doses in stable outpatients—this increases toxicity risk without improving long-term outcomes 1, 5
Evidence Quality Note
The 2014 AHA/ACC/HRS guideline 8 and 2001 ACC/AHA/ESC guideline 8 provide the foundational framework, but the most recent and specific dosing guidance comes from the 2026 Praxis Medical Insights summaries 1, which synthesize recommendations from the American Heart Association, American College of Cardiology, and European Society of Cardiology. These emphasize lower target serum concentrations (0.5–0.9 ng/mL) and more conservative dosing than older guidelines, reflecting post-DIG trial safety data showing increased mortality with higher digoxin levels. 1, 3