When should a digoxin (digitalis glycoside) assay be performed after initiation of therapy?

Timing of Digoxin Assay After Initiation

Digoxin levels should be checked early during chronic therapy in patients with normal renal function, with steady-state concentrations typically achieved in 1-3 weeks (5-7 days in patients with normal renal function), and sampling should be done at least 6-8 hours after the last dose to allow adequate time for equilibration between serum and tissue. 1, 2, 3

Timing Based on Renal Function

The timing of the first digoxin assay depends critically on the patient's renal function, as this determines when steady-state concentrations are reached:

• Normal renal function: Steady-state is achieved in approximately 5-7 days (approximately five half-lives of digoxin) 2, 3
• Impaired renal function: Steady-state may take 1-3 weeks to achieve, requiring more careful and potentially delayed monitoring 1, 2

Optimal Sampling Technique

Critical timing considerations for accurate measurement:

• Sampling must occur at least 6-8 hours after the last dose, regardless of route of administration or formulation, to allow adequate equilibration of digoxin between serum and tissue 2
• Ideally, sample just before the next scheduled dose (trough level) 2
• On once-daily dosing, concentrations will be 10-25% lower when sampled at 24 hours versus 8 hours post-dose, depending on renal function 2

Target Therapeutic Range

• Maintain serum concentration between 0.5-0.9 ng/mL for heart failure patients, as concentrations above 1.0 ng/mL have not shown superior outcomes and may increase mortality risk 4, 1, 5
• The European Society of Cardiology recommends a slightly broader range of 0.6-1.2 ng/mL 1

Special Circumstances Requiring Earlier or Additional Monitoring

Check digoxin levels sooner than steady-state when:

• Drug interactions occur: When adding medications that increase digoxin levels (amiodarone, diltiazem, verapamil, certain antibiotics, quinidine), check levels after starting these drugs 4, 1
• Signs of toxicity appear: Confusion, nausea, anorexia, visual disturbances, or cardiac arrhythmias warrant immediate level checking, especially with hypokalemia 1, 6
• Suspected digoxin toxicity: Check level immediately regardless of timing 4

Common Pitfalls to Avoid

• Do not sample too early after dosing: Sampling before 6-8 hours post-dose will yield falsely elevated levels that do not reflect tissue equilibration 2
• Do not rely on isolated measurements: Always interpret digoxin levels in the overall clinical context, as clinical response may not correlate perfectly with serum concentration 2
• Be aware of assay interferences: Endogenous digoxin-like immunoreactive substances (DLIS) and certain medications (spironolactone, Chinese medicines) can interfere with immunoassays 7

Ongoing Monitoring Strategy

• Once stable dose is established: There is no evidence that regular digoxin concentration measurements confer better outcomes 1
• Monitor when clinically indicated: Check levels when signs/symptoms of toxicity appear, when interacting drugs are added, or when renal function changes 1, 6
• If taking amiodarone: Reduce digoxin dose by 50% when amiodarone is started and monitor plasma digoxin levels closely 4