Digoxin Dosing for Atrial Fibrillation
For atrial fibrillation, initiate digoxin at 0.25 mg once daily in patients under 70 years with normal renal function, 0.125 mg daily in patients over 70 years or with impaired renal function, and 0.0625 mg daily in patients with marked renal impairment (GFR <30 mL/min). 1, 2
Initial Dosing Strategy
The standard maintenance dose for most adults under 70 years with normal renal function is 0.25 mg once daily. 3, 1, 2 This represents the typical starting point for rate control in atrial fibrillation, though loading doses are generally not required in stable outpatients. 3, 1
Age-Based Adjustments
- Patients over 70 years should receive 0.125 mg daily regardless of renal function, as advanced age indicates diminished renal clearance even with normal serum creatinine. 3, 1, 2
- Patients with low lean body mass should also receive the reduced 0.125 mg daily dose to avoid toxicity. 1, 2
Renal Function Adjustments
The dose must be adjusted based on creatinine clearance (CrCl), as digoxin is primarily renally eliminated:
- CrCl >60 mL/min and age <70 years: 0.25 mg daily 1, 2
- CrCl 30-60 mL/min or age >70 years: 0.125 mg daily 3, 1, 2
- CrCl 10-30 mL/min: 0.0625 mg daily 3, 1, 2
- CrCl <10 mL/min: 0.0625 mg daily or every other day 1
Maximum Dosing Considerations
The maximum recommended daily maintenance dose is 0.375 mg, though doses this high are rarely needed or appropriate for atrial fibrillation. 1 Most patients require only 0.125-0.25 mg daily. 1, 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 Digoxin plus beta-blocker is more effective than digoxin alone, particularly during exercise. 1
Target Therapeutic Range
The target serum digoxin concentration for atrial fibrillation is 0.6-1.2 ng/mL, though lower levels (0.5-0.9 ng/mL) are preferred to minimize toxicity risk. 1, 5, 2 Concentrations above 1.0 ng/mL offer no additional benefit and may increase mortality risk. 1
Critical Drug Interactions Requiring Dose Reduction
When amiodarone is initiated, reduce digoxin dose by 30-50% and monitor levels closely, as amiodarone predictably doubles digoxin concentrations through P-glycoprotein inhibition. 1, 6, 7
When dronedarone is initiated, reduce digoxin dose by at least 50% due to similar interaction mechanisms. 1
Other medications requiring dose reduction and monitoring include:
- Verapamil or diltiazem: reduce dose by 25-50% 1, 6
- Clarithromycin, erythromycin, azithromycin: reduce dose by 25-50% 6
- Quinidine, propafenone: reduce dose and monitor closely 1, 6
Monitoring Requirements
Check serum digoxin concentration at least 6-8 hours after the last dose to allow adequate equilibration between serum and tissue. 5, 2 On once-daily dosing, sampling at 24 hours versus 8 hours will show 10-25% lower concentrations depending on renal function. 2
Monitor serum potassium and magnesium regularly, as deficiencies increase digoxin toxicity risk even at therapeutic levels. 3, 1, 6 Target potassium 4.0-5.5 mEq/L. 6
Recheck digoxin levels when adding interacting medications such as amiodarone, calcium channel blockers, or macrolide antibiotics. 5, 6
Contraindications
Digoxin is absolutely contraindicated in:
- Second- or third-degree heart block without a permanent pacemaker 3, 1, 4
- Pre-excitation syndromes (WPW with atrial fibrillation) 3, 1
- Previous evidence of digoxin intolerance 3
Signs of Digoxin Toxicity
Cardiac manifestations include: ventricular arrhythmias, AV block, sinus bradycardia, and bidirectional ventricular tachycardia (highly specific for digoxin toxicity). 6
Gastrointestinal manifestations include: anorexia, nausea, and vomiting. 3, 6
Neurological manifestations include: visual disturbances (yellow or blurred vision), confusion, and disorientation. 3, 6
Toxicity commonly occurs with serum levels >2 ng/mL but may occur at lower levels with hypokalemia, hypomagnesemia, hypothyroidism, or hypercalcemia. 6, 4
Special Clinical Scenarios
Rapid Rate Control in Acute Atrial Fibrillation
For hemodynamically stable patients requiring rapid rate control, an IV loading dose of 0.25-0.5 mg may be given as initial bolus, followed by additional 0.25 mg doses at 6-8 hour intervals up to maximum 1.0 mg over 24 hours. 1 However, beta-blockers are superior to digoxin for acute rate control, especially during exercise. 1
Combination Therapy
Digoxin is most effective when combined with beta-blockers for rate control in atrial fibrillation, as digoxin alone often fails to control ventricular rate during exercise. 3, 1 Triple therapy (digoxin plus beta-blocker plus calcium channel blocker) may be required for adequate rate control, but monitor for excessive bradycardia. 1
Atrial Fibrillation with Heart Failure
Digoxin is particularly useful in patients with atrial fibrillation and concomitant heart failure (LVEF <40%), as it provides both rate control and modest reduction in heart failure hospitalizations without lowering blood pressure. 3, 1 This makes it valuable when hypotension limits beta-blocker use. 1
Common Pitfalls to Avoid
Do not use "therapeutic" serum levels as the sole guide for dose adjustment—clinical response (heart rate control, symptom improvement) should guide therapy. 2, 4, 8 Therapeutic levels may fail to control ventricular rate in seriously ill patients with conditions like infection, hypoxia, or recent surgery. 8
Do not administer loading doses in stable outpatients—maintenance dosing should be started directly in most clinical scenarios. 1 Steady-state concentrations will be achieved in 1-3 weeks depending on renal function. 2
Do not overlook electrolyte abnormalities—hypokalemia, hypomagnesemia, and hypercalcemia sensitize the myocardium to digoxin and increase toxicity risk even at therapeutic concentrations. 6