Epidemiology
Digoxin usage is decreasing due to its inferiority to other heart failure treatments and digoxin toxicity has, therefore, become less common; but it is at risk of being overlooked.[4]
Using 2005–2010 reports from the National Electronic Injury Surveillance System, an estimated 5156 emergency department visits for digoxin toxicity occurred annually in the US, of which >75% resulted in hospital admissions.[5] Digoxin toxicity accounted for approximately 1.0% of all emergency department visits for all adverse drug events among patients age ≥40 years; this figure was estimated to be 3.3% for patients age ≥85 years.[5]
In 2022, the American Association of Poison Control Centers reported 266 fatalities following exposure to cardiovascular drugs; digoxin was the first ranked pharmaceutical in 21 of these deaths.[6] Patients age >70 years are more at risk from digoxin toxicity even at serum digoxin levels in the recommended therapeutic range, but toxicity occurs in both young and old people.[7][8] Drug-drug interactions involving digoxin are a common cause of adverse drug effects in older people.[9] Rates of emergency department visits and hospitalization for digoxin toxicity appear to be greater for women than men.[5][10]
Young children are mainly at risk of unintentional overdose; adults are mainly at risk from intentional ingestions in a suicide attempt. Dosing errors, increased bioavailability, and decreased clearance may also result in overdose.
Risk factors
Older adults (age >70 years) are at risk for toxicity even at serum digoxin levels in the recommended therapeutic range.[7][8] Factors that may increase risk in older adults include dosing error, chronic medical conditions, decreased clearance, increased bioavailability, and interactions with other drugs.
Patients with decreased glomerular filtration rate are more susceptible to digoxin toxicity because of decreased clearance of digoxin from the serum.
Hypokalemia increases sensitivity to digoxin, resulting in symptoms in some patients with therapeutic serum concentrations of digoxin.[24]
Digoxin is largely dependent on p-glycoprotein for elimination. Thus, drugs that inhibit p-glycoprotein may increase digoxin levels and potentially cause toxicity.
These are numerous, but clinically significant ones include verapamil, diltiazem, amiodarone, quinidine, ketoconazole, itraconazole, vinblastine, doxorubicin, and erythromycin.[21] Others include clarithromycin, cyclosporine, dronedarone, mirabegron, propafenone, quinine, ritonavir, and spironolactone.
Other mechanisms may also affect digoxin levels. Amiodarone decreases renal clearance and displaces digoxin from its protein-binding sites. Quinidine is also able to displace digoxin from its protein-binding sites. Spironolactone may increase prerenal state, thereby potentiating a state of decreased renal clearance. Verapamil may decrease renal clearance. Antibiotics inhibit antibacterial activity (against gastrointestinal bacteria) and could increase the amount of digoxin absorbed from the gastrointestinal tract.
Pharmacokinetic and pharmacodynamic drug interactions with digoxin are numerous and you should consult your local drug information source for a complete list of drug-drug interactions.
Hypomagnesemia is associated with an increased susceptibility to digoxin.[7]
Hypercalcemia is associated with an increased susceptibility to digoxin.[3]
Recognized risk factor for developing digoxin toxicity.
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