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

Therapeutic Level for Digoxin

The therapeutic serum concentration range for digoxin is 0.5-1.0 ng/mL, with levels above 2.0 ng/mL commonly associated with toxicity. 1, 2

Recommended Therapeutic Range

The optimal therapeutic range for digoxin has been revised downward over time based on clinical evidence:

• Current guidelines recommend maintaining serum digoxin concentrations between 0.5-1.0 ng/mL 1, 2
• Retrospective analyses have shown that:
  • Prevention of worsening heart failure at lower concentrations (0.5-0.9 ng/mL) was as effective as higher concentrations 1
  • Risk-adjusted mortality increased as plasma concentrations exceeded 1.0 ng/mL 1
• Older therapeutic ranges (up to 2.0 ng/mL) are no longer recommended due to increased risk of adverse effects 2

Monitoring Considerations

• Serum samples should be drawn at least 6-8 hours after the last dose to ensure accurate trough levels 3
• Once-daily dosing schedules will show 10-25% lower concentrations when sampled at 24 hours versus 8 hours 3
• Regular monitoring is particularly important in:
  • Elderly patients (>70 years)
  • Patients with renal impairment
  • Patients with electrolyte abnormalities
  • Patients on medications that interact with digoxin 1, 2

Toxicity Risk Factors

Digoxin toxicity can occur even within the therapeutic range when certain risk factors are present:

• Serum levels >2.0 ng/mL are commonly associated with overt toxicity 1, 2
• Toxicity may occur at lower levels with:
  • Hypokalemia
  • Hypomagnesemia
  • Hypothyroidism 1, 2
• Drug interactions that increase digoxin levels:
  • Amiodarone
  • Verapamil
  • Clarithromycin/erythromycin
  • Itraconazole
  • Cyclosporine
  • Quinidine 1, 2

Signs of Toxicity

Monitor for these signs of digoxin toxicity:

• Cardiac: arrhythmias (including bradycardia, heart block, ventricular ectopy)
• Gastrointestinal: anorexia, nausea, vomiting
• Neurological: visual disturbances (yellow-green halos), confusion, disorientation 1, 2

Special Populations

• Elderly patients (>70 years): Target lower end of therapeutic range (0.5-0.8 ng/mL) 2, 4
• Renal impairment: Lower doses required; monitor levels more frequently 2
• Patients on multiple medications: Check for potential interactions 1

Practical Implications

• Lower maintenance doses (0.125-0.25 mg daily) are typically sufficient for most patients 1
• Elderly patients, those with renal impairment, or low lean body mass should receive lower doses (0.125 mg daily or every other day) 1
• Loading doses are generally unnecessary for chronic heart failure management 1
• Digoxin should be used cautiously or avoided in post-MI patients with ongoing ischemia 1

The current evidence strongly supports maintaining lower serum digoxin concentrations (0.5-1.0 ng/mL) to maximize benefits while minimizing the risk of toxicity.