Digoxin Dosing in Adults
Initial Dosing Strategy
For most adults under 70 years with normal renal function, initiate digoxin at 0.125–0.25 mg once daily; for patients over 70 years, those with any degree of renal impairment, or low lean body mass, start with 0.125 mg daily or lower. 1
Standard Dosing Framework
- Patients <70 years with normal renal function (CrCl ≥60 mL/min): Start 0.25 mg once daily 1, 2
- Patients ≥70 years OR any renal impairment (CrCl 30–59 mL/min): Start 0.125 mg once daily 1, 2
- Marked renal impairment (CrCl <30 mL/min) or ESRD on hemodialysis: Start 0.0625 mg once daily or every other day 1, 3, 4
Loading Doses Are Generally Not Recommended
- Loading doses should be avoided in stable outpatients with heart failure or atrial fibrillation because they provide no mortality or morbidity benefit and increase toxicity risk 1
- Loading doses may be considered only for hemodynamically stable patients requiring urgent rate control in atrial fibrillation: give 0.25–0.5 mg IV bolus initially, followed by 0.25 mg at 6–8 hour intervals, not exceeding 1.0 mg total over 24 hours 1, 2
- After IV loading, transition to oral maintenance dosing based on age and renal function 1
Target Serum Digoxin Concentrations
Maintain serum digoxin levels between 0.5–0.9 ng/mL for heart failure and 0.6–1.2 ng/mL for atrial fibrillation; concentrations above 1.0 ng/mL offer no additional benefit and increase mortality risk. 1
- For heart failure patients, the DIG trial and subsequent analyses demonstrate that levels >1.0 ng/mL are associated with increased mortality without improved outcomes 1
- Higher doses (>0.25 mg daily) are rarely needed or beneficial 1
- Serum levels should be drawn at least 6–8 hours after the last dose to allow tissue equilibration; earlier sampling underestimates true steady-state concentration 1, 2
Dose Adjustments Based on Renal Function
Digoxin clearance is primarily renal, requiring substantial dose reduction as creatinine clearance declines. 4, 2
Dosing Algorithm by Creatinine Clearance
| CrCl (mL/min) | Recommended Daily Dose | Alternative Dosing | Monitoring Frequency |
|---|---|---|---|
| ≥60 | 0.125–0.25 mg daily | Standard | Monthly after stabilization [1] |
| 30–59 | 0.0625–0.125 mg daily | Reduce by 25–50% | Every 2–3 days initially, then weekly [4] |
| 15–29 | 0.0625 mg daily | Every other day dosing acceptable | Daily until stable, then weekly [4] |
| <15 or ESRD/HD | 0.0625 mg daily or every other day | Avoid unless absolutely necessary | Daily initially, then twice weekly [3,4] |
- Use the Cockcroft-Gault equation to estimate creatinine clearance, adjusting for ideal body weight 1
- In elderly patients with low muscle mass, serum creatinine alone underestimates renal impairment 1
Mandatory Baseline Assessment Before Initiating Digoxin
Before starting digoxin, obtain baseline ECG, renal function, and serum electrolytes; second- or third-degree AV block without a pacemaker is an absolute contraindication. 1
Required Baseline Tests
- Electrocardiogram: Rule out second- or third-degree AV block, pre-excitation syndromes (Wolff-Parkinson-White), or significant sinus node dysfunction 1
- Renal function: Serum creatinine and calculated creatinine clearance to guide initial dosing 1, 4
- Serum potassium and magnesium: Target potassium 4.0–5.5 mEq/L; correct any deficiencies before starting digoxin 1
- Thyroid function: Hypothyroidism increases digoxin sensitivity and toxicity risk 1
Ongoing Monitoring Requirements
Monitor serum digoxin levels, renal function, and electrolytes regularly; frequency depends on renal function and clinical stability. 1, 4
Standard Monitoring Schedule
- Serum digoxin concentration: Check 1–2 weeks after initiation or dose change, then every 3–6 months in stable patients 1
- Renal function: Reassess every 3–6 months in stable patients; more frequently (every 2–3 days to weekly) if renal function is declining or unstable 4
- Serum potassium and magnesium: Check at each follow-up visit; hypokalemia and hypomagnesemia markedly increase toxicity risk even at therapeutic digoxin levels 1
- ECG: Repeat if new symptoms develop or when adding medications that affect AV nodal conduction 1
When to Measure Digoxin Levels
- Routinely 1–2 weeks after starting or changing dose 1
- When adding medications that increase digoxin levels (see Drug Interactions section) 1
- Immediately if signs of toxicity appear 1
- Not routinely needed in stable patients with good clinical response 5
Drug Interactions Requiring Dose Reduction
Reduce digoxin dose by 30–50% when co-administered with amiodarone, verapamil, diltiazem, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, or quinidine. 1, 3, 2
Specific Dose Adjustments
- Amiodarone or verapamil: Reduce digoxin dose by 30–50% 1, 6
- Dronedarone: Reduce digoxin dose by ≥50% 1
- Azithromycin: Unlike erythromycin or clarithromycin, azithromycin has minimal interaction with digoxin and does not require routine dose adjustment in standard-risk patients, though monitoring is still advised 1
- When N-desethylamiodarone (active metabolite of amiodarone) concentrations are high (>600 ng/mL) in patients with CrCl ≤30 mL/min, consider reducing digoxin to 0.03125 mg daily 6
Absolute Contraindications
Do not use digoxin in patients with second- or third-degree AV block without a permanent pacemaker, pre-excitation syndromes (e.g., Wolff-Parkinson-White with atrial fibrillation), or prior documented digoxin intolerance. 1
Additional Relative Contraindications (Use with Extreme Caution)
- Decompensated heart failure with hypotension or cardiogenic shock 1
- Acute myocardial infarction 1
- Uncorrected hypokalemia, hypomagnesemia, or hypothyroidism 1
- Severe renal impairment (CrCl <15 mL/min) unless absolutely necessary with intensive monitoring 4
Clinical Indications for Digoxin
Heart Failure with Reduced Ejection Fraction (HFrEF)
- Digoxin reduces hospitalizations but does not reduce mortality in HFrEF patients (Class 2b recommendation, Level B-R evidence) 1, 5
- Consider digoxin for symptomatic patients (NYHA class II–IV) with LVEF <40% who remain symptomatic despite guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists) 1
- Digoxin is particularly useful when hypotension limits beta-blocker titration 1
Atrial Fibrillation
- Digoxin is most appropriate for rate control in atrial fibrillation when combined with beta-blockers, as digoxin alone is ineffective during exercise due to its vagally-mediated mechanism 1
- Digoxin monotherapy may be acceptable in sedentary elderly patients or those with concomitant heart failure 1, 7
- Do not use digoxin as monotherapy for rate control in active patients; beta-blockers are superior, especially during exercise 1
Recognition and Management of Digoxin Toxicity
Digoxin toxicity can occur at therapeutic levels when precipitating factors such as hypokalemia, hypomagnesemia, hypothyroidism, renal impairment, or interacting medications are present. 1
Clinical Manifestations of Toxicity
- Cardiac: Ventricular ectopy, AV block, bradycardia, bidirectional ventricular tachycardia 1
- Gastrointestinal (often earliest signs): Anorexia, nausea, vomiting, diarrhea 1
- Neurological: Visual disturbances (yellow-tinted or blurred vision), confusion, disorientation, delirium, weakness 1
Risk Factors for Toxicity
- Serum digoxin concentration >2 ng/mL (though toxicity may occur at lower levels) 1, 5
- Hypokalemia (potassium <4.0 mEq/L) 1
- Hypomagnesemia 1
- Hypothyroidism 1
- Renal impairment 1, 4
- Concomitant use of interacting medications 1
Management of Suspected Toxicity
- Immediately measure serum digoxin level (≥6–8 hours post-dose), potassium, magnesium, and renal function 1
- Obtain ECG to assess for conduction abnormalities or arrhythmias 1
- Correct electrolyte abnormalities (target potassium 4.0–5.5 mEq/L) 1
- Consider digoxin-specific Fab antibody fragments for life-threatening ventricular arrhythmias 1
- Withhold digoxin until toxicity resolves, then restart at a lower dose if still indicated 1
Special Populations
Elderly Patients (≥70 Years)
- Never exceed 0.125 mg daily in patients ≥75 years, even with normal renal function; the conventional adult dose of 0.25 mg daily is inappropriate for most elderly patients 1
- Age-related decline in renal function increases digoxin half-life from approximately 37 hours in younger adults to 70 hours in elderly patients 7
- Elderly patients have reduced total-body clearance and increased sensitivity to digoxin 7
- Initiating or continuing digoxin in elderly patients without baseline testing and ongoing monitoring is unsafe due to multiple toxicity risk factors 1
End-Stage Renal Disease on Hemodialysis
- Digoxin can be used cautiously in ESRD patients on hemodialysis, but requires significantly reduced dosing (0.0625 mg daily or every other day) and mandatory serum level monitoring 3
- Target serum concentration 0.5–0.9 ng/mL 3
- Digoxin is associated with increased mortality risk in ESRD, particularly in patients with low predialysis potassium levels 3
- Consider alternative agents when possible 3
Patients with Low Lean Body Mass
- Calculate digoxin loading and maintenance doses based on ideal body weight, not actual body weight 1, 2
- Patients with low lean body mass require lower doses (typically 0.0625–0.125 mg daily) 1
Common Pitfalls and How to Avoid Them
Pitfall 1: Using Standard Adult Doses in Elderly or Renally Impaired Patients
- Always reduce the initial dose to 0.125 mg daily or lower in patients ≥70 years or with any degree of renal impairment 1
- Calculate creatinine clearance using Cockcroft-Gault equation, not just serum creatinine 1
Pitfall 2: Measuring Digoxin Levels Too Soon After Dosing
- Wait at least 6–8 hours after the last dose before drawing serum digoxin levels; earlier sampling underestimates true steady-state concentration 1, 2
- Steady-state is reached in approximately 5 half-lives (1–3 weeks depending on renal function) 2
Pitfall 3: Failing to Correct Electrolyte Abnormalities
- Always correct hypokalemia and hypomagnesemia before starting digoxin and monitor electrolytes regularly 1
- Toxicity can occur at therapeutic digoxin levels when potassium or magnesium are low 1, 5
Pitfall 4: Not Adjusting Dose When Adding Interacting Medications
- Reduce digoxin dose by 30–50% when starting amiodarone, verapamil, diltiazem, or macrolide antibiotics (except azithromycin) 1, 3
- Measure digoxin level 1–2 weeks after adding any interacting medication 1
Pitfall 5: Using Digoxin Monotherapy for Rate Control in Active Patients with Atrial Fibrillation
- Digoxin alone is ineffective for controlling ventricular rate during exercise; always combine with a beta-blocker in active patients 1
- Digoxin monotherapy may be acceptable only in sedentary elderly patients or those with concomitant heart failure 1, 7