Therapeutic Levels of Digoxin

Recommended Therapeutic Range

The American Heart Association recommends maintaining digoxin serum concentrations between 0.5 to 1.0 ng/mL for optimal clinical benefit with minimal risk of toxicity 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

Overt digitalis toxicity is commonly associated with serum digoxin levels greater than 2.0 ng/mL 3
However, toxicity may occur at lower digoxin levels in the presence of hypokalemia, hypomagnesemia, or hypothyroidism 3
Concomitant use of medications that increase digoxin levels (such as clarithromycin, erythromycin, amiodarone, itraconazole, cyclosporine, verapamil, or quinidine) may also increase the risk of toxicity 3, 2

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 or when signs or symptoms of toxicity appear (such as confusion, nausea, anorexia, visual disturbances, or cardiac arrhythmias) 2

Therapy is commonly initiated and maintained at a dose of 0.125 to 0.25 mg daily 3
Lower doses (0.125 mg daily or every other day) should be used for patients over 70 years of age, patients with impaired renal function, or patients with low lean body mass 3

Levels of digoxin previously considered therapeutic (up to 2.0 ng/mL) may exert deleterious cardiovascular effects in the long term 4
Women may not benefit from digoxin therapy and may be at increased risk for death with such therapy 4
Digoxin should be used with caution or not at all in post-MI patients, particularly those with ongoing ischemia 4

Overt toxicity is commonly associated with levels >2.0 ng/mL, but toxicity can occur at lower levels in the presence of hypokalemia, hypomagnesemia, hypothyroidism, or drug interactions 5
For rapid digitalization in acute settings, administer 0.25-0.5 mg IV initially, followed by additional 0.25 mg doses at 6-8 hour intervals, up to a maximum of 1.0 mg over 24 hours, as recommended by the American College of Cardiology 5
When digoxin is combined with amiodarone, reduce digoxin dose by 30-50%, and when combined with dronedarone, reduce digoxin dose by at least 50%, according to the American Heart Association guidelines 5
Absolute contraindications for digoxin include second or third-degree AV block without permanent pacemaker, and pre-excitation syndromes (WPW with AF/atrial flutter), as stated by the American College of Cardiology 5