What is the appropriate loading dose of digoxin (digitalis glycoside) in the elderly?

From the Guidelines

Digoxin loading in elderly patients is not recommended, and instead, a low maintenance dose of 0.125 mg daily or every other day should be used initially. For elderly patients, the goal is to avoid rapid loading doses and high serum concentrations, which can increase the risk of toxicity 1. The elderly have reduced renal function, decreased lean body mass, and altered volume of distribution, making them more susceptible to digoxin toxicity.

Key Considerations

• Before initiating therapy, obtain baseline serum creatinine, potassium, magnesium, and calcium levels, as these electrolyte abnormalities can increase digoxin toxicity risk 1.
• Monitor serum digoxin levels after 7-14 days of therapy, aiming for a therapeutic range of 0.5-0.9 ng/mL for heart failure (lower than the traditional 0.8-2.0 ng/mL) 1.
• Watch for signs of toxicity including nausea, visual disturbances, confusion, and cardiac arrhythmias.
• Numerous drug interactions exist with digoxin, particularly with amiodarone, verapamil, and certain antibiotics, which may necessitate further dose reductions 1.
• Regular monitoring of renal function and electrolytes is essential throughout treatment.

Maintenance Dosing

• Maintenance doses <0.125 mg/day for any indication in people ≥75 years without renal impairment are recommended 1.
• Serum plasma levels >1.0 ng/mL have no additional benefit and may increase toxicity, particularly in women.
• Risk factors of toxicity include hypokalaemia, hypomagnesaemia, hypercalcaemia, CKD, hypoxia, acidosis, hypothyroidism, and myocardial ischaemia 1.

From the FDA Drug Label

Digitalization may be accomplished by either of two general approaches that vary in dosage and frequency of administration, but reach the same endpoint in terms of total amount of digoxin accumulated in the body. Rapid Digitalization with a Loading Dose: The loading dose should be administered in several portions, with roughly half the total given as the first dose. Additional fractions of this planned total dose may be given at 6 to 8-hour intervals, with careful assessment of clinical response before each additional dose A single initial dose of 500 to 750 mcg (0.5 to 0.75 mg) of digoxin tablets usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours. Additional doses of 125 to 375 mcg (0. 125 to 0.375 mg) may be given cautiously at 6 to 8-hour intervals until clinical evidence of an adequate effect is noted. Therapy is generally initiated at a dose of 250 mcg (0. 25 mg) once daily in patients under age 70 with good renal function, at a dose of 125 mcg (0.125 mg) once daily in patients over age 70 or with impaired renal function, and at a dose of 62.5 mcg (0. 0625 mg) in patients with marked renal impairment.

To load digoxin in the elderly, the recommended approach is to use a loading dose administered in several portions, with roughly half the total given as the first dose. The initial dose can be between 500 to 750 mcg (0.5 to 0.75 mg), followed by additional doses of 125 to 375 mcg (0.125 to 0.375 mg) at 6 to 8-hour intervals, as needed and based on clinical response. For elderly patients (over 70 years old) with impaired renal function, the initial dose should be 125 mcg (0.125 mg) once daily, and for those with marked renal impairment, the dose should be 62.5 mcg (0.0625 mg) 2.

From the Research

Loading Digoxin in Elderly Patients

To load digoxin in elderly patients, several factors must be considered, including the patient's renal function, age, and ideal body weight.

• The dosage equation HUGE_DIG can be used to calculate the initial digoxin dose to reach a specific target serum digoxin concentration (SDC) 3.
• This equation is: Digoxin (mg/day) = 0.091 - 0.006 x HUGE, where HUGE is a value used to differentiate the presence or absence of chronic kidney disease in elderly patients.
• The study found that the calculated digoxin doses with this equation were administered in the prospective phase and no statistical differences were observed between measured and desired SDCs 3.
• Another study suggested that digoxin dosing should be individualized based on target levels and not solely on clinical signs and symptoms, taking into account the patient's clearance creatinine and ideal body weight 4.
• It is also important to consider the changes in renal physiology secondary to aging and not merely the estimated glomerular filtration rate when loading digoxin in elderly patients 3, 5.
• Additionally, the use of digoxin in elderly patients requires careful interpretation of serum digoxin assay and consideration of its intrinsic limitations, as well as the potential for multidrug interactions 5, 6.
• A conservative dosing strategy and therapeutic monitoring are necessary when using digoxin in elderly patients due to their reduced elimination of the drug 6, 7.