What is the recommended dose and frequency of digoxin (digitalis glycoside) for adults with atrial fibrillation or heart failure?

Recommended Dose and Frequency of Digoxin for Adults with Atrial Fibrillation or Heart Failure

For adults with atrial fibrillation or heart failure, the recommended starting dose of digoxin is 0.25 mg once daily for patients under 70 years with good renal function, 0.125 mg once daily for patients over 70 years or with impaired renal function, and 0.0625 mg daily for patients with marked renal impairment. 1, 2

Initial Dosing Strategy

Loading Dose (for Rapid Digitalization)

• If rapid digitalization is medically necessary, a loading dose can be administered in divided portions 1:
  • Initial dose of 500-750 mcg (0.5-0.75 mg)
  • Additional doses of 125-375 mcg (0.125-0.375 mg) at 6-8 hour intervals until clinical effect is achieved 1
  • For a 70 kg patient, the usual amount required to achieve 8-12 mcg/kg peak body stores is 750-1250 mcg (0.75-1.25 mg) 1

Maintenance Dosing

• For heart failure patients 3, 2, 1:
  • 0.25 mg once daily for patients under 70 years with normal renal function
  • 0.125 mg once daily for patients over 70 years or with impaired renal function
  • 0.0625 mg daily for patients with marked renal impairment
• For atrial fibrillation with rapid ventricular rate 3, 2:
  • Similar dosing as heart failure, but typically used in combination with beta-blockers
  • Higher doses (0.375-0.50 mg daily) are rarely needed or recommended 2, 4

Dose Adjustments Based on Patient Factors

Renal Function

• Maintenance dose should be calculated based on creatinine clearance 1:
  • Maintenance Dose = Peak Body Stores × (14 + Ccr/5)/100
  • Where Ccr is creatinine clearance corrected to 70 kg body weight 1
• For patients with renal impairment, steady state may take longer to achieve, requiring more careful monitoring 5

Age

• Patients over 70 years should receive lower doses (0.125 mg daily) due to decreased clearance 2, 1, 6
• Elderly patients have significantly increased digoxin half-life (mean 69.6 hours vs 36.8 hours in younger patients) and decreased clearance 6

Drug Interactions

• Reduce digoxin dose when used with medications that increase digoxin levels 3, 5, 2:
  • Amiodarone (reduce by 30-50%)
  • Dronedarone (reduce by at least 50%)
  • Verapamil, diltiazem, quinidine, certain antibiotics 3, 5

Therapeutic Monitoring

Target Serum Concentration

• The therapeutic serum concentration should be maintained between 0.6-1.2 ng/mL 3, 5
• For heart failure patients, target concentration of 0.5-0.9 ng/mL is recommended 2
• Serum concentrations ≥1.2 ng/mL are associated with a 56% increased hazard of mortality 7

Monitoring Schedule

• Check digoxin concentration early during chronic therapy in patients with normal renal function 5
• No evidence that regular digoxin concentration measurements confer better outcomes once a stable dose is established 5
• Monitor when adding medications that may increase digoxin levels 5
• Check levels immediately if signs of toxicity appear (confusion, nausea, anorexia, visual disturbances, arrhythmias) 3, 5

Contraindications and Cautions

Absolute Contraindications

• Second or third-degree heart block without a permanent pacemaker 3, 4
• Pre-excitation syndromes 3
• Previous evidence of digoxin intolerance 3

Cautions

• Hypokalemia increases risk of digoxin toxicity; monitor electrolytes regularly 3, 4
• Use with caution in patients receiving other drugs with AV nodal-blocking properties 3, 4
• Sinus node dysfunction 3
• Hepatic dysfunction 3

Adverse Effects to Monitor

• Cardiac arrhythmias (sinoatrial and AV block, atrial and ventricular arrhythmias) 3
• Gastrointestinal symptoms (anorexia, nausea, vomiting) 3, 4
• Neurological complaints (confusion, visual disturbances including color vision distortion) 3, 2

By following these dosing recommendations and monitoring parameters, clinicians can optimize the safety and efficacy of digoxin therapy for patients with atrial fibrillation or heart failure.