What are the precautions and contraindications for using Digoxin (digitalis glycoside) in patients?

From the Guidelines

Digoxin should be used with caution in patients with heart failure, and its use requires careful consideration of several contraindications and precautions, including kidney disease, electrolyte imbalances, and drug interactions, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. When administering digoxin, it is essential to consider the following precautions:

• Avoid using digoxin in patients with ventricular fibrillation, ventricular tachycardia (unless heart failure is present), and complete heart block without a pacemaker.
• Use low doses (0.125 mg daily or every other day) in patients over 70 years old, with impaired renal function, or with a low lean body mass, as recommended in the 2022 AHA/ACC/HFSA guideline 1.
• Correct electrolyte imbalances, particularly hypokalemia, hypomagnesemia, and hypercalcemia, before starting digoxin, as these increase toxicity risk.
• Monitor serum digoxin levels (therapeutic range 0.8-2.0 ng/mL), electrolytes, and kidney function regularly, with dose adjustments made accordingly.
• Be aware of numerous drug interactions, including with amiodarone, verapamil, quinidine, and certain antibiotics, which can increase serum levels.
• Patients with thyroid disorders require special attention, as hypothyroidism increases sensitivity while hyperthyroidism may reduce effectiveness. Some key points to consider when using digoxin include:
• The risk of death is independently associated with serum digoxin concentration, with a significantly higher risk observed in those with concentrations ≥1.2 ng/mL and ≥1.6 ng/mL, as reported in the 2022 AHA/ACC/HFSA guideline 1.
• Therapy with digoxin may either be continued in the absence of a contraindication or discontinued with caution, as stated in the 2022 AHA/ACC/HFSA guideline 1.
• Clinical worsening after withdrawal of digoxin has been shown, highlighting the need for careful consideration when discontinuing the medication, as noted in the 2022 AHA/ACC/HFSA guideline 1.

From the FDA Drug Label

PRECAUTIONS Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin Use in Patients with Impaired Renal Function: In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2. 0 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to digoxin. Hypercalcemia from any cause predisposes the patient to digitalis toxicity Hypothyroidism may reduce the requirements for digoxin. Digoxin should be used with caution in patients with acute myocardial infarction. It may be desirable to reduce the dose of digoxin for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias

The precautions for using Digoxin include:

• Using smaller doses in patients with impaired renal function
• Maintaining normal serum potassium and magnesium concentrations to avoid toxicity
• Avoiding hypercalcemia as it predisposes to digitalis toxicity
• Using with caution in hypothyroidism as it may reduce the requirements for digoxin
• Using with caution in acute myocardial infarction to avoid undesirable increases in myocardial oxygen demand and ischemia
• Reducing the dose prior to electrical cardioversion to avoid ventricular arrhythmias

The contraindications for using Digoxin include:

• Ventricular fibrillation
• Known hypersensitivity to digoxin
• Hypersensitivity reaction to other digitalis preparations [ 2 ]

From the Research

Precautions for Using Digoxin

• Digoxin should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function, such as amiodarone or a beta-blocker 3.
• The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients, with lower doses used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass 3.
• Digoxin toxicity is commonly associated with serum levels >2 ng/mL, but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist 3.
• The concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity 3.

Contraindications for Using Digoxin

• Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker 3.
• Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure 3.
• Patients with cardiac amyloidosis should be carefully selected and monitored during digoxin administration, as digoxin use is discouraged due to a reported increased risk of sensitivity and toxicity 4.

Special Considerations

• Patients with impaired renal function should be closely monitored during treatment with digoxin, as they may be at greater risk for digoxin toxicity 5, 6.
• Plasma digoxin concentration measurements may be useful in identifying digitalis sensitivity in patients with toxicity associated with low plasma digoxin concentrations, but have limited value in the diagnosis of digitalis toxicity 7.
• Caution should be exercised when administering potassium to patients with digitalis toxicity, as high potassium values may be found in patients with serum digoxin levels above 6 ng/ml 6.