digoxin and spironolactone

Spironolactone increases digoxin plasma concentrations by inhibiting P-glycoprotein mediated renal tubular secretion and possibly by reducing tubular secretion. Additionally, spironolactone is a potassium sparing diuretic that can cause hyperkalaemia, which may potentiate digoxin induced cardiac toxicity. The combined effect on digoxin levels and electrolyte balance increases the risk of adverse cardiac events.

Elevated digoxin levels can lead to digoxin toxicity characterised by nausea, anorexia, visual disturbances and cardiac arrhythmias. Hyperkalaemia, particularly in patients with renal impairment or those taking other potassium sparing agents, can further increase the risk of bradycardia and atrioventricular block. The interaction is clinically significant and requires careful monitoring.

Monitor serum digoxin concentrations, serum potassium and renal function before starting spironolactone and at regular intervals thereafter. Adjust the digoxin dose as needed to maintain therapeutic levels. Consider alternative diuretics if the patient is at high risk of hyperkalaemia or digoxin toxicity. Advise patients to report symptoms of toxicity such as nausea or palpitations.

This interaction is well documented in multiple pharmacokinetic studies and clinical reports. The effect of spironolactone on digoxin levels is consistent and is included in major drug interaction references.