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

Therapeutic Digoxin Level

The therapeutic serum digoxin concentration ranges from 0.8 to 2.0 ng/mL for most adult patients, though lower concentrations of 0.5-0.9 ng/mL are now preferred in elderly patients and those with heart failure. 1, 2

Optimal Therapeutic Ranges

• Heart failure patients: 0.5-0.9 ng/mL is now the preferred range 1
• Atrial fibrillation: 0.8-2.0 ng/mL 2
• Elderly patients (≥65 years): 0.5-0.9 ng/mL 3
• Children: 1.0-2.5 ng/mL 3

Clinical Significance of Digoxin Levels

Efficacy Considerations

• Levels below 0.8 ng/mL may still provide clinical benefits in some patients 4
• The American College of Cardiology/American Heart Association guidelines note that levels of digoxin greater than 1.0 ng/mL were not associated with superior outcomes 5
• Lower serum concentrations (0.5-0.9 ng/mL) are now preferred, especially in elderly patients, as they provide therapeutic benefit with reduced toxicity risk 1

Toxicity Considerations

• Overt digoxin toxicity is commonly associated with serum levels >2.0 ng/mL 5
• About 87% of patients with clinical toxicity have levels above 2.0 ng/mL 6
• Toxicity can occur even at lower levels if the following coexist:
  • Hypokalemia
  • Hypomagnesemia
  • Hypothyroidism 5

Factors Affecting Digoxin Levels

Patient Factors

1. Renal function: Digoxin is primarily eliminated by the kidneys; impaired renal function increases serum levels 1, 4
2. Age: Elderly patients have reduced renal function and lean body mass, requiring lower doses 1, 4
3. Body weight: Dosing should be based on lean (ideal) body weight 4
4. Comorbidities: Severe pulmonary disease or electrolyte disturbances can increase sensitivity 7

Drug Interactions

Dose reduction is necessary when co-administered with:

• Verapamil, clarithromycin, erythromycin (30-50% reduction) 1
• Amiodarone, itraconazole (30-50% reduction) 1
• Dronedarone (at least 50% reduction) 1
• Quinidine (can increase digoxin levels 2-3 fold) 2

Monitoring Recommendations

• Sample blood just before the next scheduled dose or at least 6-8 hours after the last dose 4
• On a once-daily dosing schedule, concentrations will be 10-25% lower at 24 hours versus 8 hours 4
• Regular monitoring is especially important in elderly patients, those with renal impairment, or patients on interacting medications 1, 3

Common Pitfalls

1. Incorrect sampling time: Levels drawn too soon after administration may be falsely elevated 4
2. Failure to adjust for renal function: A major cause of toxicity 7
3. Overlooking drug interactions: Can lead to unexpected toxicity 1
4. Relying solely on serum levels: Clinical context must always be considered; some patients show toxicity below 2.0 ng/mL 6
5. Using excessive doses in elderly patients: 45% of elderly patients receive doses higher than the recommended 0.125 mg/day 3

The interpretation of digoxin levels should always be made in the context of the patient's clinical status, renal function, electrolyte balance, and concomitant medications rather than relying solely on the numerical value.