Should digoxin (digitalis glycoside) be held in an asymptomatic patient with a serum digoxin level of 3.0 and normal renal function (creatinine 0.7)?

From the Guidelines

You should hold the digoxin as the level of 3.0 ng/mL is above the therapeutic range and represents toxicity, even though the patient is currently asymptomatic. The normal creatinine of 0.7 mg/dL indicates good kidney function, which is not the cause of the elevated digoxin level. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, digoxin levels above 1.2 ng/mL and 1.6 ng/mL are associated with a significantly higher risk of death. When digoxin levels exceed 2.0 ng/mL, there is an increased risk of developing toxicity symptoms including nausea, vomiting, visual disturbances, confusion, and dangerous cardiac arrhythmias.

Key Considerations

• The patient should be monitored closely for the development of symptoms, and an ECG should be obtained to check for cardiac abnormalities such as bradycardia or arrhythmias.
• Digoxin should not be restarted until levels fall into the therapeutic range and the physician provides further guidance on dosing adjustments.
• The benefit of digoxin in patients with HF remains controversial, and guideline-directed medical therapy (GDMT) is expected to be optimized before considering the addition of digoxin 1.

Recommendations

• Contact the prescribing physician immediately to report this elevated level.
• Consider alternative treatments for heart failure, as the use of digoxin is rarely required and potentially detrimental at higher doses 1.

From the FDA Drug Label

About two-thirds of adults considered adequately digitalized (without evidence of toxicity) have serum digoxin concentrations ranging from 0.8 to 2. 0 ng/mL. However, digoxin may produce clinical benefits even at serum concentrations below this range. About two-thirds of adult patients with clinical toxicity have serum digoxin concentrations greater than 2.0 ng/mL. Consequently, 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

The patient has a digoxin level of 3.0 ng/mL, which is above the range of 0.8 to 2.0 ng/mL. Although the patient is asymptomatic, the elevated digoxin level increases the risk of toxicity.

• Key consideration: The serum creatinine level is 0.7 mg/dL, indicating relatively normal renal function.
• Clinical decision: Given the elevated digoxin level, it is prudent to hold the next dose and monitor the patient's condition closely to avoid potential toxicity 2.

From the Research

Digoxin Level and Toxicity

• The patient has a digoxin level of 3.0 ng/mL and is asymptomatic with a creatinine level of 0.7 mg/dL.
• According to a study published in 1997 3, a retrospective analysis of 1,269 patients on digoxin found that 58 patients had serum digoxin levels of 3.0 ng/ml or higher, and only 11 of these patients showed clinical evidence of digoxin toxicity.
• Another study from 1998 4 found that patients with serum digoxin levels >2.4 ng/mL were slightly older and had greater serum creatinine levels than those with levels < or =2.4 ng/mL, suggesting that impaired renal function may contribute to high digoxin levels.
• A review article from 2020 5 highlights the narrow therapeutic window of digoxin and its potential for cardiotoxicity, emphasizing the importance of careful monitoring and appropriate therapy regimens.

Management of Digoxin Toxicity

• A study from 2016 6 discusses the management of digoxin toxicity, including the use of digoxin-specific antibody fragments, which are safe and effective in severe toxicity.
• The same study notes that monitoring should continue after treatment due to the risk of rebound toxicity, and that restarting therapy should take into account the indication for digoxin and any reasons why the concentration became toxic.
• An article from 2008 7 emphasizes the importance of a high index of suspicion for early recognition and appropriate management of digoxin toxicity, as signs and symptoms are often nonspecific.

Holding Digoxin

• Given the patient's asymptomatic status and relatively normal creatinine level, the decision to hold digoxin should be based on individual clinical judgment and careful monitoring of the patient's condition.
• The study from 1997 3 suggests that some patients may tolerate high digoxin levels without exhibiting toxic effects, but this should not be taken as a guarantee, and careful monitoring is still necessary.