Epidemiology
Digoxin toxicity has been reported in 0.04% of patients admitted as acute cases to hospital. In one population-based cohort study in the Netherlands, the incidence rate for admissions due to digoxin toxicity was 48.5 in 100,000 prescriptions (1.94 admissions in 1000 treatment years).[2]
The National Poisons Information Service in the UK reported in 2022-2023 that digoxin was the 4th most commonly involved agent in their consultant referrals (after paracetamol, 'unknown agents', and drugs of misuse). National Poisons Information Service: report 2022 to 2023 Opens in new window
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 admission to hospital.[3] Digoxin toxicity accounted for approximately 1.0% of all emergency department visits in the US for all adverse drug events among patients aged ≥40 years; this figure was estimated to be 3.3% for patients aged ≥85 years.[3]
Patients aged >55 years are more at risk of toxicity than younger people, but toxicity occurs in both young and old people.[4][5] Drug-drug interactions involving digoxin are a common cause of adverse drug effects in older people.[6] Rate of emergency department visits and hospitalisation for digoxin toxicity appear to be greater for women than men.[2][3]
Risk factors
Older adults (aged >55 years) are at risk for toxicity from a number of mechanisms, such as chronic medical conditions, decreased clearance, increased bioavailability, and interaction with other chronic medications.[4]
Patients with decreased glomerular filtration rate are more susceptible to digoxin toxicity because of decreased clearance of digoxin from the serum.
Patients with hyperkalaemia (>5.0 mmol/L [>5.0 mEq/L]) are more at risk of dysrhythmias and cardiac arrest, leading to a worse prognosis. However, acute digoxin toxicity can also cause hyperkalaemia. Severe hyperkalaemia (>6.5 mmol/L [>6.5 mEq/L]) is a marker of the urgent need to give digoxin-specific antibody (Fab) fragments in addition to standard therapy to treat hyperkalaemia (see Management recommendations).[1] Other causes of hyperkalaemia include haemolysis, renal failure, and use of ACE inhibitors.
Hypokalaemia (<3.0 to 3.5 mmol/L [<3.0 to 3.5 mEq/L]) can exacerbate features of digoxin toxicity, such as arrhythmias.
Digoxin is largely dependent on p-glycoprotein for elimination. Thus, medications 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.[17] Others include clarithromycin, ciclosporin, propafenone, 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 decrease renal clearance of digoxin. Verapamil may decrease renal clearance. Antibiotics inhibit antibacterial activity (against gastrointestinal bacteria) and could increase the amount of digoxin absorbed from the gastrointestinal tract.
Hypomagnesaemia increases susceptibility to digoxin.
Hypercalcaemia increases susceptibility to digoxin.
Recognised risk factor for developing digoxin toxicity.
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