What workup is needed to prescribe digoxin (Digitalis glycoside)?

From the Guidelines

To prescribe digoxin safely, a comprehensive workup including a thorough medical history, physical examination, laboratory tests (serum electrolytes, renal function tests, liver function tests, and baseline ECG), and assessment for potential drug interactions is essential. This approach is supported by the 2022 AHA/ACC/HFSA guideline for the management of heart failure, which emphasizes the importance of optimizing guideline-directed medical therapy (GDMT) before considering the addition of digoxin 1.

When initiating digoxin therapy, it is crucial to start with a low dose, typically 0.125 to 0.25 mg daily, and use even lower doses (0.125 mg daily or every other day) for patients over 70 years of age, as higher doses are rarely required and may be detrimental 1. The workup should include:

• A thorough medical history focusing on cardiac conditions, renal function, and medication use
• A physical examination with attention to vital signs, heart sounds, and signs of heart failure
• Laboratory tests such as serum electrolytes (particularly potassium, magnesium, and calcium), renal function tests (BUN and creatinine), liver function tests, and a baseline ECG to assess heart rhythm and conduction
• For patients with heart failure, an echocardiogram to evaluate cardiac function and structure
• Assessment for potential drug interactions, especially with medications that affect digoxin levels or increase the risk of toxicity

After initiating therapy, regular monitoring of digoxin levels (with a therapeutic range of 0.8-2.0 ng/mL), renal function, and electrolytes is necessary to minimize the risk of toxicity, given digoxin's narrow therapeutic window 1. This comprehensive approach is vital for minimizing morbidity, mortality, and improving quality of life in patients prescribed digoxin.

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

Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg)

The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination. The following formula has had wide clinical use: Maintenance Dose = Peak Body Stores (i.e., Loading Dose) x % Daily Loss/100 Where: % Daily Loss = 14 + Ccr/5 (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m body surface area.)

The workup needed to prescribe digoxin includes:

• Serum creatinine concentrations to estimate creatinine clearance (Ccr)
• Lean body weight to determine the appropriate dose
• Assessment of renal function to adjust the dose accordingly
• Monitoring of serum digoxin concentrations to ensure therapeutic levels and minimize the risk of toxicity
• Clinical evaluation to assess the patient's response to the drug and adjust the dose as needed. 2

From the Research

Workup Needed to Prescribe Digoxin

To prescribe digoxin, a thorough workup is necessary to ensure safe and effective use. The following factors should be considered:

• Renal function: Digoxin is primarily eliminated through the kidneys, and impaired renal function can lead to increased serum concentrations and toxicity 3, 4, 5.
• Serum electrolyte levels: Abnormal levels of potassium, sodium, and calcium can affect digoxin pharmacokinetics and increase the risk of toxicity 6.
• Age: Older adults (≥ 65 years) may require lower doses of digoxin due to decreased renal function and increased sensitivity to the drug 7, 4.
• Medication interactions: Certain medications, such as quinidine, amiodarone, and verapamil, can alter digoxin pharmacokinetics and increase the risk of toxicity 3.
• Clinical status: Patients with heart failure or atrial fibrillation should be closely monitored for signs of digoxin toxicity, such as arrhythmias or gastrointestinal symptoms 3, 7, 6.

Laboratory Tests

The following laboratory tests are recommended to monitor digoxin therapy:

• Serum digoxin concentration: This should be measured regularly to ensure that the concentration is within the therapeutic range (0.5-0.9 ng/mL for older adults, 0.8-2.0 ng/mL for adults) 3, 7, 6.
• Renal function tests: Serum creatinine and cystatin C levels should be measured to assess renal function and estimate glomerular filtration rate (GFR) 4, 5.
• Serum electrolyte levels: Potassium, sodium, and calcium levels should be monitored regularly to detect any abnormalities that may affect digoxin pharmacokinetics 6.

Dosing Considerations

The dose of digoxin should be individualized based on the patient's renal function, age, and clinical status. The following dosing considerations should be taken into account:

• Older adults (≥ 65 years): Lower doses (0.125 mg/day or less) may be necessary due to decreased renal function and increased sensitivity to the drug 7, 4.
• Renal impairment: The dose of digoxin should be adjusted based on the patient's renal function, with lower doses used in patients with impaired renal function 3, 4, 5.
• Medication interactions: The dose of digoxin may need to be adjusted if the patient is taking medications that interact with digoxin, such as quinidine or amiodarone 3.