What is the therapeutic level of digoxin (digitalis glycoside)?

Therapeutic Levels of Digoxin

The therapeutic serum concentration of digoxin should be maintained between 0.5 to 1.0 ng/mL for optimal clinical benefit with minimal risk of toxicity. 1, 2

Recommended Therapeutic Range

• Current evidence supports maintaining digoxin serum concentrations between 0.5 to 1.0 ng/mL, which is lower than previously recommended ranges 1, 2
• The European Society of Cardiology recommends a slightly wider range of 0.6 to 1.2 ng/mL for chronic therapy in patients with normal renal function 2
• Retrospective analyses show that prevention of worsening heart failure by digoxin at lower concentrations (0.5 to 0.9 ng/mL) was as effective as that achieved at higher concentrations 1
• Risk-adjusted mortality increased as plasma concentrations exceeded 1.0 ng/mL in retrospective analysis of the Digitalis Investigation Group trial 1

Toxicity Thresholds

• Overt digitalis toxicity is commonly associated with serum digoxin levels greater than 2.0 ng/mL 1, 3
• However, toxicity may occur at lower digoxin levels in the presence of:
  • Hypokalemia 1
  • Hypomagnesemia 1
  • Hypothyroidism 1
  • Concomitant use of medications that increase digoxin levels (clarithromycin, erythromycin, amiodarone, itraconazole, cyclosporine, verapamil, or quinidine) 1, 2

Monitoring Recommendations

• Initial monitoring should be performed early during chronic therapy, especially in patients with renal impairment who may take longer to reach steady state 2
• Monitoring should be performed when:
  • Adding medications that may increase digoxin levels 2
  • Signs or symptoms of toxicity appear (confusion, nausea, anorexia, visual disturbances, cardiac arrhythmias) 2
• Regular monitoring is not necessary once a stable dose is established, as there is no evidence that it confers better outcomes 2

Dosing Considerations

• 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 for:
  • Patients over 70 years of age 1
  • Patients with impaired renal function 1
  • Patients with low lean body mass 1
• Higher doses (0.375 to 0.50 mg daily) are rarely needed or recommended 1
• Loading doses are not necessary for initiating therapy in patients with heart failure 1

Common Pitfalls and Caveats

• Levels of digoxin previously considered therapeutic (up to 2.0 ng/mL) may exert deleterious cardiovascular effects in the long term 1
• Women may not benefit from digoxin therapy and may be at increased risk for death with such therapy 1
• Digoxin should be used with caution or not at all in post-MI patients, particularly those with ongoing ischemia 1
• Sampling for serum concentrations should be done just before the next scheduled dose or at least 6-8 hours after the last dose to allow for equilibration between serum and tissue 3
• Older adults (≥65 years) have shown more supra-therapeutic concentrations and adverse events, suggesting they may benefit from the lower end of the therapeutic range (0.5-0.9 ng/mL) 4