What is the maximum dose of digoxin (digitalis glycoside) for treating heart failure?

From the Guidelines

The maximum dose of digoxin for treating heart failure is typically 0.125-0.25 mg daily for maintenance therapy. Dosing should be individualized based on patient factors including renal function, age, body weight, and concomitant medications. Lower doses (0.125 mg daily or even every other day) are recommended for elderly patients, those with impaired kidney function, or patients with low body weight. Serum digoxin levels should be monitored, with therapeutic levels generally considered to be 0.5-0.9 ng/mL for heart failure, as suggested by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• Higher doses (e.g., digoxin 0.375 to 0.50 mg daily) are rarely used or needed in the management of patients with HF.
• There is no reason to use loading doses of digoxin to initiate therapy in patients with HF.
• The concomitant use of certain drugs can increase serum digoxin concentrations and may increase the likelihood of digitalis toxicity, as noted in the 2013 ACCF/AHA guideline for the management of heart failure 1.
• Potassium levels should be maintained in the normal range as hypokalemia increases the risk of digoxin toxicity.

Monitoring and Safety

• Careful monitoring is essential due to digoxin's narrow therapeutic window, with toxicity potentially causing nausea, visual disturbances, confusion, and dangerous cardiac arrhythmias.
• Overt digitalis toxicity is commonly associated with serum digoxin levels greater than 2 ng per mL, but toxicity may occur with lower digoxin levels, especially if hypokalemia, hypomagnesemia, or hypothyroidism coexists, as discussed in the 2005 ACC/aha guideline update for the diagnosis and management of chronic heart failure in the adult 1.

Clinical Decision Making

• The decision to use digoxin should be made with caution, considering the potential benefits and risks, and the availability of other treatments with more favorable risk-benefit profiles, as suggested by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
• The most recent and highest quality study, the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life as outcomes.

From the FDA Drug Label

The doses of digoxin used in controlled trials in patients with heart failure have ranged from 125 to 500 mcg (0.125 to 0.5 mg) once daily. Therapy is generally initiated at a dose of 250 mcg (0. 25 mg) once daily in patients under age 70 with good renal function, at a dose of 125 mcg (0.125 mg) once daily in patients over age 70 or with impaired renal function, and at a dose of 62.5 mcg (0. 0625 mg) in patients with marked renal impairment. Doses may be increased every 2 weeks according to clinical response.

The maximum dose of digoxin for treating heart failure is 500 mcg (0.5 mg) once daily.

• The dose should be titrated according to the patient’s age, lean body weight, and renal function.
• The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination 2.

From the Research

Maximum Dose of Digoxin for Heart Failure

The maximum dose of digoxin for treating heart failure is not explicitly stated in the provided studies. However, the studies provide information on the dosing recommendations and strategies for digoxin in patients with heart failure.

• The study by 3 developed a new method to determine the initial dose of digoxin in patients with heart failure, which takes into account the patient's creatinine clearance, ideal body weight, and target digoxin concentration.
• The study by 4 established a population pharmacokinetic model of digoxin in older patients with heart failure and chronic kidney disease, and recommended doses of 62.5 and 125 μg for patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m².
• The study by 5 compared the effects of angiotensin-converting enzyme (ACE) inhibitors and digoxin in patients with heart failure, and suggested that digoxin is best reserved for patients with atrial fibrillation and a rapid ventricular response, and for those whose heart failure is not controlled with an ACE inhibitor plus a diuretic.
• The study by 6 examined the efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status, and found that digoxin reduced heart failure hospitalization in both patients with and without diabetes.
• The study by 7 developed a mnemonic (BANDAID²) to summarize the evidence-based treatments for systolic heart failure, which includes digoxin as one of the treatments with strong evidence for its use.

Dosing Recommendations

Based on the studies, the following dosing recommendations can be made:

• For older patients with heart failure and chronic kidney disease, doses of 62.5 and 125 μg may be recommended, depending on the patient's eGFR 4.
• For patients with heart failure and reduced ejection fraction, digoxin may be used to reduce heart failure hospitalization, especially in those with diabetes 6.
• For patients with systolic heart failure, digoxin may be used as part of a comprehensive treatment strategy that includes other evidence-based therapies, such as beta-blockers, ACE inhibitors, and diuretics 7.