When to check serum digoxin (digitalis glycoside) levels?

From the Guidelines

Digoxin levels should be checked 6-8 hours after the last dose in patients on oral therapy, or 12-24 hours after an intravenous dose, with routine monitoring recommended 7-14 days after initiating therapy or changing the dose, and then every 3-6 months for stable patients, as supported by the 2013 ACCF/AHA guideline for the management of heart failure 1. The therapeutic range for most indications is 0.8-2.0 ng/mL, though lower ranges (0.5-0.9 ng/mL) are often targeted for heart failure, as suggested by the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1. Some key points to consider when checking digoxin levels include:

• More frequent monitoring is necessary for patients with risk factors such as renal impairment, electrolyte disturbances (especially low potassium, magnesium, or high calcium), thyroid disorders, or those taking medications that interact with digoxin, as noted in the 2013 ACCF/AHA guideline for the management of heart failure 1.
• The concomitant use of clarithromycin, erythromycin, amiodarone, itraconazole, cyclosporine, verapamil, or quinidine can increase serum digoxin concentrations and may increase the likelihood of digitalis toxicity, as reported in the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1.
• A low lean body mass and impaired renal function can also elevate serum digoxin levels, which may explain the increased risk of digitalis toxicity in elderly patients, as discussed in the 2013 ACCF/AHA guideline for the management of heart failure 1.
• Symptoms of toxicity like nausea, visual disturbances, confusion, or new arrhythmias should prompt immediate level checking regardless of the routine schedule, as emphasized in the example answers. It is essential to prioritize the single most recent and highest quality study, which in this case is the 2013 ACCF/AHA guideline for the management of heart failure 1, to ensure that the recommendation is based on the strongest and most recent evidence.

From the FDA Drug Label

To allow adequate time for equilibration of digoxin between serum and tissue, sampling of serum concentrations should be done just before the next scheduled dose of the drug. If this is not possible, sampling should be done at least 6 to 8 hours after the last dose, regardless of the route of administration or the formulation used

• Timing of serum digoxin concentration sampling:
  • Should be done just before the next scheduled dose of the drug
  • If not possible, sampling should be done at least 6 to 8 hours after the last dose
  • This allows for adequate time for equilibration of digoxin between serum and tissue 2
• Key consideration: The serum concentration of digoxin should always be interpreted in the overall clinical context, and an isolated measurement should not be used alone as the basis for increasing or decreasing the dose of the drug.

From the Research

Digoxin Level Checks

• Digoxin levels should be checked in patients with signs of toxicity, such as life-threatening tachy-bradyarrhythmias, hyperkalaemia (> 6 mmol/L), or haemodynamic instability with an elevated digoxin concentration (> 2 μg/L or 2.6 nmol/L) 3.
• Serum digoxin levels alone may not be a reliable guide for diagnosing digoxin toxicity in the presence of hypokalemia, as patients with hypokalemia can experience toxicity even at low serum digoxin levels 4.
• There are currently no universally accepted guidelines for the management of digoxin toxicity, but a consensus approach recommends early recognition of signs of potentially life-threatening toxicity and immediate treatment with digoxin-specific antibodies 5.

Timing of Digoxin Level Checks

• In acute poisoning, digoxin levels may not accurately reflect the total body load of digoxin, as distribution may not be complete until around 6 hours after ingestion 3.
• In chronic poisoning, digoxin levels should be interpreted with caution, as variation in volume of distribution due to factors such as lean body weight, age, and renal failure can lead to overestimation of the required dose of digoxin-specific antibody fragments 3.

Factors Influencing Digoxin Levels

• Hypokalemia can increase the risk of digoxin toxicity, even at low serum digoxin levels, and is often caused by the use of large doses of diuretics 4.
• Renal failure can prolong the half-life of digoxin and digoxin-specific antibody fragments, leading to increased toxicity and reduced efficacy of treatment 3.