What is the maximum dosing of digoxin (Digitalis glycoside) for atrial fibrillation (AFib) in patients with End-Stage Renal Disease (ESRD) on dialysis?

From the Guidelines

For patients with atrial fibrillation who are on dialysis for end-stage renal disease (ESRD), the maximum recommended digoxin dose is 0.125 mg daily, with careful monitoring of serum levels and avoidance of initial loading doses, as supported by the 2013 ACCF/AHA guideline for the management of heart failure 1. When managing atrial fibrillation in patients with ESRD on dialysis, it is crucial to consider the reduced renal clearance of digoxin, which can lead to drug accumulation and increased risk of toxicity.

• The target serum digoxin concentrations should be maintained between 0.5-0.9 ng/mL, as suggested by the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1.
• Regular monitoring of digoxin levels is essential, ideally 12-24 hours after a dose and before dialysis sessions, as the drug is not significantly removed by dialysis.
• Careful attention should be paid to potential signs of toxicity, including nausea, visual disturbances, confusion, and cardiac arrhythmias, which may prompt immediate evaluation and possible dose adjustment.
• Additionally, consideration should be given to the potential for electrolyte abnormalities, particularly potassium fluctuations, which can potentiate digoxin toxicity in ESRD patients.
• A more recent guideline from 2015 on heart failure management in skilled nursing facilities also supports starting digoxin at a low dose, such as 0.125 mg every other day, in frail older patients with renal insufficiency 1.

From the FDA Drug Label

Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg) The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination. % Daily Loss = 14 + Ccr/5 (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m body surface area.) Table 5 provides average daily maintenance dose requirements of digoxin tablets for patients with heart failure based upon lean body weight and renal function

For patients with End-Stage Renal Disease (ESRD) on dialysis, the creatinine clearance (Ccr) is effectively 0 mL/min. Using the formula % Daily Loss = 14 + Ccr/5, we get % Daily Loss = 14 + 0/5 = 14. The maintenance dose can be calculated as Maintenance Dose = Peak Body Stores x % Daily Loss/100. Assuming a conservative peak body store of 6 to 10 mcg/kg for patients with renal insufficiency, and using a % Daily Loss of 14, the maintenance dose would be:

• For a 70 kg patient with a peak body store of 6 mcg/kg: Maintenance Dose = 6 mcg/kg x 70 kg x 14/100 = 58.8 mcg
• For a 70 kg patient with a peak body store of 10 mcg/kg: Maintenance Dose = 10 mcg/kg x 70 kg x 14/100 = 98 mcg Given the provided dosing information in Table 5, the maximum dosing of digoxin for atrial fibrillation (AFib) in patients with End-Stage Renal Disease (ESRD) on dialysis would be approximately 62.5 to 125 mcg (0.0625 to 0.125 mg) daily 2.

From the Research

Maximum Dosing of Digoxin for Atrial Fibrillation in ESRD Patients on Dialysis

• There are no research papers to assist in answering this question, as the provided studies focus on anticoagulation for atrial fibrillation in patients with end-stage renal disease on dialysis, rather than the maximum dosing of digoxin 3, 4, 5, 6, 7.
• The studies discuss the epidemiology of atrial fibrillation in dialysis patients, the effectiveness of oral anticoagulation, and the potential use of direct oral anticoagulants in this population, but do not provide information on digoxin dosing 3, 4, 5.
• Some studies examine the incidence of atrial fibrillation in patients with end-stage renal disease on hemodialysis versus peritoneal dialysis, but do not address digoxin dosing 6.
• Overall, the available evidence does not provide guidance on the maximum dosing of digoxin for atrial fibrillation in patients with end-stage renal disease on dialysis 3, 4, 5, 6, 7.