What is the procedure to check digoxin (digitalis glycoside) levels?

Procedure to Check Digoxin Level

Draw a serum sample at least 6 to 8 hours after the last digoxin dose, or ideally just before the next scheduled dose, to allow adequate time for equilibration between serum and tissue. 1

Timing of Blood Draw

• The critical factor is waiting at least 6-8 hours post-dose to avoid falsely elevated levels that reflect distribution phase rather than steady-state concentrations 1
• Sampling just before the next scheduled dose (trough level) provides the most reliable measurement for therapeutic monitoring 1
• On once-daily dosing, digoxin concentration will be 10-25% lower when sampled at 24 hours versus 8 hours post-dose, depending on renal function 1
• On twice-daily dosing schedules, there are only minor differences whether sampling occurs at 8 or 12 hours after a dose 1

Laboratory Method

• Serum digoxin levels are measured using immunoassay techniques, most commonly radioimmunoassay, enzyme immunoassay, chemiluminescence immunoassay, or fluorescence polarization immunoassay 2
• The assay sensitivity typically allows detection of digoxin levels as low as 0.05-0.5 ng/mL depending on the method used 2, 3

Target Therapeutic Range

• Aim for serum concentrations between 0.5 to 1.0 ng/mL for optimal clinical benefit with minimal toxicity risk 4, 5
• Retrospective analyses demonstrate that lower concentrations (0.5-0.9 ng/mL) are as effective as higher concentrations for preventing worsening heart failure 4
• Risk-adjusted mortality increases when plasma concentrations exceed 1.0 ng/mL 4, 5
• Overt toxicity is commonly associated with levels greater than 2.0 ng/mL, though toxicity can occur at lower levels in the presence of hypokalemia, hypomagnesemia, or hypothyroidism 4, 5, 6

When to Check Levels

• Initial monitoring should occur early during chronic therapy, especially in patients with renal impairment who take longer to reach steady state 5
• Steady-state concentrations are achieved in approximately 5 half-lives (1-3 weeks depending on renal function) 1
• Check levels when adding medications that increase digoxin concentrations (clarithromycin, erythromycin, amiodarone, itraconazole, cyclosporine, verapamil, quinidine, propafenone, dronedarone) 4, 5, 6
• Monitor when signs or symptoms of toxicity appear: cardiac arrhythmias, confusion, nausea, anorexia, visual disturbances (blurred or yellow vision) 5, 6

Common Pitfalls

• Do not sample too soon after dosing - this is the most common error and yields falsely elevated levels that do not reflect therapeutic effect 1
• Serum digoxin concentration may decrease acutely during periods of exercise without any change in clinical efficacy due to increased binding to skeletal muscle 1
• Always interpret levels in clinical context - about one-third of patients with clinical toxicity have concentrations less than 2.0 ng/mL, so values below 2.0 ng/mL do not rule out toxicity 1
• Some patients cannot tolerate digoxin even at serum concentrations below 0.8 ng/mL 1
• Cross-reactivity with certain substances (including spironolactone with some older assays) can confound results 4
• Serial assessment of serum digoxin levels is unnecessary in most stable patients - routine monitoring is not required once therapeutic dosing is established 7