What are the standing orders for digoxin (digitalis glycoside) therapy?

Standing Orders for Digoxin Therapy

In patients with symptomatic heart failure with reduced ejection fraction (HFrEF) despite guideline-directed medical therapy (GDMT), digoxin might be considered at a dose of 0.125-0.25 mg daily to decrease hospitalizations for heart failure, with lower doses for elderly patients, those with renal impairment, or low lean body mass. 1

Patient Selection

• Digoxin should be reserved for patients with HFrEF who remain symptomatic despite optimization of GDMT, or who are unable to tolerate GDMT 1
• The benefit of digoxin in patients on current GDMT is unclear because most trials preceded current heart failure therapies 1
• Digoxin is also indicated for control of ventricular response rate in patients with chronic atrial fibrillation, often in combination with beta-blockers 2, 3

Dosing Recommendations

• Therapy is commonly initiated and maintained at a dose of 0.125 to 0.25 mg daily 1
• Lower doses (0.125 mg daily or every other day) should be used initially if the patient is >70 years of age, has impaired renal function, or has a low lean body mass 1, 2
• Higher doses (0.375-0.50 mg daily) are rarely used or needed in the management of heart failure 1, 2

Target Serum Concentrations

• The target serum digoxin concentration should be 0.5-0.9 ng/mL 2, 4
• Retrospective analyses have shown a linear relationship between mortality and digoxin serum concentration, with significantly higher risk observed in those with concentrations ≥1.2 ng/mL 1
• Serum levels above 1.0 ng/mL have not shown superior outcomes and may increase mortality risk 2, 5

Monitoring Requirements

• Regular monitoring of serum digoxin levels, renal function, and electrolytes (particularly potassium and magnesium) is recommended 2, 4
• Monitoring is especially important when adding medications that may increase digoxin levels 2
• Check levels immediately if signs of toxicity appear (cardiac arrhythmias, gastrointestinal symptoms, neurological complaints) 2, 6

Contraindications and Cautions

• Digoxin is contraindicated in patients with significant sinus or atrioventricular block without a permanent pacemaker 1, 2
• The drug should be used cautiously in patients taking other drugs that can depress sinus or atrioventricular nodal function or affect digoxin levels (e.g., amiodarone, verapamil, beta-blockers) 1, 2
• Pre-existing pre-excitation syndromes are a contraindication for digoxin therapy 2
• Caution should be exercised in patients with hypokalemia, hypomagnesemia, or hypothyroidism 2

Dose Adjustments for Drug Interactions

• Reduce digoxin dose when used with medications that increase digoxin levels, such as amiodarone (reduce by 30-50%) and dronedarone (reduce by at least 50%) 2
• Dose adjustments are needed when switching between different digoxin formulations due to differences in bioavailability 3

Management of Toxicity

• Digoxin toxicity is commonly associated with serum levels >2.0 ng/mL and requires immediate intervention 7
• Treatment with digoxin-specific antibody fragments (Digibind) is recommended for severe toxicity 7
• When resuming digoxin after toxicity resolves, use a lower dose with a target serum concentration of 0.5-0.9 ng/mL 7

Clinical Evidence and Efficacy

• To date, only one large-scale randomized controlled trial of digoxin in heart failure has been conducted, which showed no effect on mortality but modestly reduced the combined risk of death and hospitalization 1
• The trial found no significant effect on health-related quality of life 1
• Retrospective analyses and meta-analyses have supported the effect of digoxin on reducing hospitalizations 1
• Clinical worsening after withdrawal of digoxin has been observed in some patients 1