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2.2.3 Potassium-sparing diuretics and aldosterone antagonists

Potassium-sparing diuretics

1st choiceAmiloride tablets 5mg

Aldosterone antagonists (mineralocorticoid receptor antagonists-MRAs)
1st choiceSpironolactone tablets 12.5mg, 25mg, 50mg, 100mg

Prescribing Notes

  • These agents have a weak diuretic effect if given alone but their effects are additive with thiazides and loop diuretics.
  • Amiloride (5-20mg) is a weak, potassium-sparing diuretic. It is usually reserved for those already receiving thiazide or loop diuretics in whom hypokalaemia is a concern. Amiloride may take 2-3 days for full effect.
  • Amiloride is also used in resistant hypertension under specialist supervision.
  • Spironolactone 25mg daily has been shown to reduce mortality in patients with moderate to severe heart failure (NYHA Stage III) who are already receiving standard therapy including ACE inhibitors and diuretics.
  • Spironolactone may be associated with significant hyperkalaemia or renal impairment particularly in combination with ACE inhibitors or other diuretics. U&Es should be checked at baseline, 1 week after initiation (and after every dose increase), monthly for first 3 months, then every 3 months for 1 year, and then every 6 months thereafter. Patients should be warned of the risk of hyperkalaemia in the setting of volume depletion and of the signs and symptoms of hyperkalaemia. See MHRA warning and recommendations.


  • Eplerenone is an alternative aldosterone receptor antagonist that is less likely to produce sexual side effects such as gynaecomastia, breast pain or menstrual irregularities.
  • Eplenerone is the only aldosterone antagonist licensed for use as an adjunct in left ventricular dysfunction with evidence of heart failure after a myocardial infarction
    • It is the first choice aldosterone antagonist for this indication. See NICE NG185
    • For other indications, eplerenone is usually reserved as a substitute for spironolactone in patients with heart failure who cannot tolerate spironolactone, e.g. if they develop gynaecomastia.


  • Potassium-sparing diuretics should be used with caution in renal impairment.
  • Elderly patients are particularly susceptible to the side-effects of diuretics.
  • Diuretics should not be used on a long term basis to treat simple gravitational oedema. This will usually respond to increased ambulation, raising the legs and support stockings.
  • Avoid concurrent NSAID: risk of acute kidney injury.
  • Potassium supplements should not (unless under close supervision and monitoring) be given with: potassium sparing diuretics, aldosterone antagonists, in the presence of renal failure, with ACE inhibitors or with angiotensin-II receptor antagonists, due to the danger of hyperkalaemia.
  • Counsel patients on ‘sick day guidance’ with diuretics – click here for further information.