When to Check a Digoxin Level
Check a digoxin serum concentration at steady state (5–7 days after starting or adjusting the dose), when adding or stopping interacting medications, when renal function declines (eGFR <60 mL/min/1.73 m² or acute kidney injury develops), when electrolyte abnormalities occur, whenever toxicity is suspected, and in elderly or frail patients who are at heightened risk. 1, 2
Timing of Digoxin Level Measurement
At Steady State After Initiation or Dose Change
- Measure the serum digoxin concentration 5–7 days (approximately five half-lives) after starting therapy or adjusting the dose to allow equilibration between serum and tissue. 3
- In patients with normal renal function, steady state is typically reached in 1 week; in those with renal impairment, it may take up to 3 weeks. 3
Correct Sampling Technique
- Draw blood at least 6–8 hours after the last dose, ideally just before the next scheduled dose (trough level), to avoid falsely elevated concentrations during the distribution phase. 1, 2, 3
- Sampling earlier than 6 hours will overestimate the true steady-state level and lead to inappropriate dose reductions. 1, 2
Clinical Scenarios Requiring Digoxin Level Monitoring
When Interacting Medications Are Added or Stopped
- Check a digoxin level 24–48 hours after starting or completing a course of P-glycoprotein inhibitors such as amiodarone, verapamil, diltiazem, dronedarone, quinidine, clarithromycin, erythromycin, itraconazole, cyclosporine, or propafenone. 1, 2
- These agents can increase digoxin concentrations by 30–50% (or ≥50% with dronedarone), necessitating empiric dose reduction and close monitoring. 1, 2
- For azithromycin, routine level monitoring is not required in standard-risk patients during a typical 5-day course, but should be considered in high-risk individuals (age ≥70 years, renal impairment, low lean body mass, or electrolyte abnormalities). 1
With Declining Renal Function
- Measure digoxin levels whenever eGFR falls below 60 mL/min/1.73 m² or when acute kidney injury develops, because digoxin is primarily renally excreted and impaired clearance raises toxicity risk. 1, 2
- Reassess renal function and digoxin concentration regularly in elderly patients, as age-related decline in creatinine clearance may not be reflected by serum creatinine alone. 1, 2
With Electrolyte Abnormalities
- Check a digoxin level immediately when hypokalemia (<4.0 mEq/L), hypomagnesemia, or hypercalcemia is detected, because these disturbances sensitize the myocardium to digoxin and can precipitate toxicity even at therapeutic serum concentrations. 1, 2
- Maintain serum potassium between 4.0–5.5 mEq/L and correct magnesium deficits before and during digoxin therapy. 1, 2
When Toxicity Is Suspected
- Measure the digoxin level immediately if any signs of toxicity appear: cardiac arrhythmias (ventricular ectopy, AV block, bradycardia, bidirectional ventricular tachycardia), gastrointestinal symptoms (anorexia, nausea, vomiting), or neurological symptoms (visual disturbances, confusion, disorientation). 1, 2
- Toxicity can occur at concentrations <2 ng/mL when precipitating factors such as electrolyte abnormalities, hypothyroidism, renal dysfunction, or interacting medications are present. 1, 2
In Elderly or Frail Patients
- Check a baseline digoxin level 5–7 days after initiation in all patients ≥70 years of age, those with low lean body mass, or those with any degree of renal impairment, because these populations are at markedly higher risk of toxicity. 1, 2
- In elderly patients, do not exceed a maintenance dose of 0.125 mg daily without measuring a level, as higher doses are associated with increased mortality. 1, 2
Target Therapeutic Ranges
Heart Failure
- Target serum digoxin concentration: 0.5–0.9 ng/mL. 1, 2
- Concentrations >1.0 ng/mL offer no additional clinical benefit and are associated with increased mortality risk. 1, 2
Atrial Fibrillation
- Target serum digoxin concentration: 0.6–1.2 ng/mL, though lower levels (0.5–0.9 ng/mL) are increasingly preferred based on post-DIG trial safety data. 1, 2
When Routine Monitoring Is Not Required
Stable Patients on Maintenance Therapy
- Serial assessment of serum digoxin levels is unnecessary in most stable patients who are clinically well, have adequate rate control (60–100 bpm at rest, <110 bpm with activity), and have no changes in renal function, electrolytes, or concomitant medications. 1, 2, 4
- The radioimmunoassay was developed to assist in the evaluation of toxicity, not efficacy; there is little relationship between serum digoxin concentration and therapeutic effects in stable patients. 4
After Loading Doses in Stable Outpatients
- Loading doses are generally not required in stable outpatients with heart failure or atrial fibrillation and provide no mortality or morbidity benefit; maintenance dosing should be started directly. 1, 2
- If a loading dose is administered in an urgent inpatient setting, measure the digoxin level 6–8 hours after the last dose to guide subsequent maintenance dosing. 1, 2
Common Pitfalls
Incorrect Sampling Time
- Drawing blood <6 hours after a dose will yield falsely elevated concentrations during the distribution phase, leading to inappropriate dose reductions. 1, 2, 3
Ignoring Clinical Context
- An isolated digoxin level should never be used alone as the basis for increasing or decreasing the dose; always interpret the concentration in the overall clinical context, including renal function, electrolytes, symptoms, and concomitant medications. 3
Failure to Adjust for Renal Function
- In patients with renal impairment, do not assume steady state has been reached at 5–7 days; it may take up to 3 weeks, and premature sampling will underestimate the true steady-state concentration. 3