Digoxin Dosing and Contraindications
Weight-Based Dosing
Digoxin dosing is not primarily weight-based for maintenance therapy; instead, dose selection depends on age, renal function, and lean body mass, with standard doses of 0.125–0.25 mg daily for most adults. 1, 2
- For patients under 70 years with normal renal function and normal lean body mass, start with 0.25 mg once daily. 1, 2
- For patients with low lean body mass (regardless of total body weight), reduce the initial dose to 0.125 mg daily because digoxin distributes into lean tissue, not adipose tissue, and low muscle mass increases the risk of toxicity. 1, 2
- Loading doses, when required for acute rate control, should be calculated using ideal body weight at 8–12 µg/kg IBW, not actual body weight, with a maximum total loading dose of 1.0 mg over 24 hours. 1
- Do not exceed 12 µg/kg IBW for loading doses, as higher doses produce serum concentrations ≥1.2 ng/mL in approximately 50% of patients and increase mortality without improving efficacy. 1
Age-Based Dosing Adjustments
Patients aged 70 years or older require substantially lower digoxin doses—typically 0.125 mg daily or less—because age-related reductions in renal clearance and lean body mass markedly increase digoxin half-life and toxicity risk. 1, 2
- In elderly patients (≥70 years), digoxin half-life increases from approximately 37 hours to 70 hours, and total-body clearance decreases by more than 50% compared with younger adults. 3
- For patients ≥75 years, the maintenance dose should never exceed 0.125 mg daily, even with normal measured creatinine clearance, because serum creatinine underestimates renal impairment in elderly individuals with reduced muscle mass. 1
- Loading doses should be avoided entirely in stable elderly outpatients with heart failure or atrial fibrillation, as they provide no mortality or morbidity benefit and substantially increase toxicity risk. 1, 2
Renal Function–Based Dosing Algorithm
Digoxin is primarily renally excreted, and dose reduction is mandatory in any degree of renal impairment to prevent life-threatening toxicity. 1, 2
Dosing by Creatinine Clearance (CrCl):
| CrCl (mL/min) | Recommended Maintenance Dose | Frequency |
|---|---|---|
| ≥60 (age <70 years) | 0.125–0.25 mg | Once daily [1,2] |
| ≥60 (age ≥70 years) | 0.125 mg | Once daily [1,2] |
| 30–59 | 0.0625–0.125 mg | Once daily [1,2] |
| 15–29 | 0.0625 mg | Once daily or every other day [1,2] |
| <15 (not on dialysis) | 0.0625 mg | Every other day [1,2] |
- Estimate renal function using the Cockcroft–Gault equation adjusted to an assumed body weight of 70 kg for dosing calculations, because serum creatinine alone grossly underestimates impairment in elderly patients with low lean body mass. 1
- For patients with CrCl <30 mL/min, consider avoiding digoxin entirely unless absolutely necessary, as the risk of toxicity is extremely high. 1, 2
- When advanced renal impairment (CrCl 15–30 mL/min) coexists with age ≥70 years or low body weight, start with 0.0625 mg every other day and monitor closely. 1, 2
Therapeutic Target Serum Concentrations
Target serum digoxin concentrations of 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 provide no additional benefit and increase mortality. 1, 2
- Serum digoxin levels should be drawn at least 6–8 hours after the last dose to allow equilibration between serum and tissue; earlier draws underestimate the true steady-state level. 1
- Do not routinely monitor digoxin levels in stable patients; measure levels only when adding interacting medications, suspecting toxicity, or adjusting doses in high-risk patients. 1, 2
Absolute Contraindications
Digoxin is absolutely contraindicated in the following clinical scenarios, where administration may precipitate life-threatening arrhythmias or complete heart block: 1, 2
- Second- or third-degree atrioventricular (AV) block without a permanent pacemaker, because digoxin further depresses AV nodal conduction and may cause asystole. 1, 2, 4
- Pre-excitation syndromes (e.g., Wolff–Parkinson–White) with atrial fibrillation or atrial flutter, because digoxin shortens the refractory period of the accessory pathway and can trigger ventricular fibrillation. 1, 2, 4
- Ventricular fibrillation, as digoxin exacerbates this arrhythmia. 1
- Known hypersensitivity to digoxin or any digitalis preparation. 1
- Prior documented digoxin intolerance or toxicity. 1, 2
Relative Contraindications and High-Risk Scenarios
Use digoxin with extreme caution—or avoid entirely—in the following situations: 1, 2
- Concomitant use of other AV nodal–blocking agents (e.g., beta-blockers, amiodarone, verapamil, diltiazem), as additive AV block may occur; if combination therapy is necessary, use the lowest effective doses and monitor closely. 1, 2, 5
- Suspected sick sinus syndrome, where digoxin may worsen sinus node dysfunction. 1
- Uncorrected hypokalemia or hypomagnesemia, which sensitize the myocardium to digoxin and precipitate toxicity even at therapeutic serum concentrations. 1, 2
- Hypothyroidism, which lowers digoxin requirements and increases toxicity risk. 1, 2
- Acute myocardial infarction or decompensated heart failure with hypotension or cardiogenic shock, where digoxin is not indicated for acute stabilization. 1, 5
Mandatory Baseline and Ongoing Monitoring
Before initiating digoxin, obtain the following baseline assessments to identify contraindications and guide safe dosing: 1, 2
- Baseline electrocardiogram to rule out second- or third-degree AV block or pre-excitation syndromes. 1, 2
- Serum creatinine and estimated creatinine clearance (using Cockcroft–Gault) to guide dose selection. 1, 2
- Serum potassium and magnesium, with correction to target ranges (potassium 4.0–5.5 mEq/L) before starting digoxin. 1, 2
- Thyroid function tests (TSH), as hypothyroidism increases toxicity risk. 1
During therapy, monitor the following at each follow-up visit: 1, 2
- Serum potassium and magnesium at every visit, with prompt correction of any deficits. 1, 2
- Renal function (creatinine clearance) regularly, particularly in elderly patients, to adjust dosing as kidney function declines. 1, 2
- Repeat ECGs to detect new rhythm disturbances or progression of conduction disease. 1
- Serum digoxin concentration when adding interacting medications (e.g., amiodarone, verapamil, clarithromycin) or when signs of toxicity appear. 1, 2
Drug Interactions Requiring Dose Reduction
Reduce digoxin dose by 30–50% when co-administered with the following P-glycoprotein or CYP3A4 inhibitors, and monitor serum levels closely: 1, 2, 4
- Amiodarone: reduce digoxin dose by 30–50%. 1, 2, 4
- Dronedarone: reduce digoxin dose by ≥50%. 1, 2
- Verapamil or diltiazem: reduce digoxin dose by 30–50%. 1, 2
- Macrolide antibiotics (clarithromycin, erythromycin): reduce dose and monitor levels. 1, 2
- Azithromycin has a substantially lower interaction risk than erythromycin or clarithromycin and does not require routine dose adjustment in standard-risk patients, but monitor high-risk patients (elderly, renal impairment, low potassium) for toxicity. 1
- Itraconazole, cyclosporine, propafenone, quinidine: reduce dose by 30–50%. 1, 2
Clinical Signs of Digoxin Toxicity
Digoxin toxicity can occur at serum concentrations <2 ng/mL—or even within the therapeutic range—when precipitating factors such as hypokalemia, hypomagnesemia, hypothyroidism, renal impairment, or interacting medications are present. 1, 2
Typical Manifestations by System:
| System | Signs and Symptoms |
|---|---|
| Cardiac | Ventricular ectopy, AV block, bradycardia, bidirectional ventricular tachycardia [1,2] |
| Gastrointestinal | Anorexia, nausea, vomiting (often the earliest signs) [1,2] |
| Neurological | Visual disturbances (yellow-tinted or blurred vision), confusion, disorientation, delirium [1,2] |
- Suspect toxicity immediately if any of these symptoms appear, check serum digoxin level, potassium, magnesium, and renal function, and consider digoxin-specific Fab antibody fragments for life-threatening ventricular arrhythmias. 1
Common Pitfalls and How to Avoid Them
- Do not use digoxin as monotherapy for rate control in atrial fibrillation during exercise, as its vagally mediated effect is insufficient; always combine with a beta-blocker for effective control. 1, 2
- Never administer loading doses to stable outpatients with heart failure or atrial fibrillation, as they offer no mortality or morbidity benefit and markedly increase toxicity risk. 1, 2
- Do not exceed 0.25 mg daily in the majority of patients, as higher doses (0.375–0.5 mg daily) are rarely needed and are associated with increased mortality. 1, 2
- Always confirm correct timing of blood draws (≥6–8 hours post-dose) before interpreting digoxin levels or adjusting doses. 1
- Correct electrolyte abnormalities before starting digoxin, as hypokalemia and hypomagnesemia precipitate toxicity even at therapeutic serum concentrations. 1, 2