Spironolactone

Spironolactone is an aldosterone antagonist and potassium-sparing diuretic. It inhibits the action of the hormone aldosterone, which is responsible for water and salt retention. Unlike furosemide and torasemide, spironolactone does not cause potassium loss; instead, it conserves potassium.

The RALES study showed that low-dose spironolactone reduces mortality by 30% in severe heart failure – a groundbreaking result. Spironolactone is used for heart failure, treatment-resistant high blood pressure, liver cirrhosis with ascites, and primary hyperaldosteronism.

Spironolactone also has antiandrogenic properties, which are used off-label in women to treat hormonal acne and hirsutism, but in men can lead to gynecomastia (breast enlargement).

Spironolactone blocks the mineralocorticoid receptor (aldosterone receptor):

Mechanism of action:

• Competitive inhibition of aldosterone at the mineralocorticoid receptor
• Aldosterone can no longer trigger sodium reabsorption and potassium secretion
• Sodium and water are excreted
• Potassium is conserved (potassium-sparing diuretic)

In heart failure:

• Prevents the harmful effects of aldosterone on the heart
• Reduces cardiac fibrosis (scarring)
• Improves endothelial function
• Reduces mortality by 30% (RALES study)

Antiandrogenic effect:

• Blocks androgen receptors
• Inhibits testosterone production
• In women, can: improve acne and hirsutism (off-label use)
• In men, can: cause gynecomastia and erectile dysfunction

Onset of action: Slow onset of action over 2-3 days. Full effect only after 1-2 weeks. Long duration of action due to the active metabolite canrenone (half-life 16-20 hours).

Spironolactone is suitable for:

• Chronic heart failure (NYHA III-IV, as add-on therapy)
• Treatment-resistant high blood pressure (as a 4th medication)
• Primary hyperaldosteronism (Conn syndrome)
• Liver cirrhosis with ascites and edema
• Hypokalemia caused by other diuretics

Especially recommended for:

• Severe heart failure
• High blood pressure that does not respond to 3 medications
• Conn syndrome (aldosterone-producing adenoma)
• Liver cirrhosis with ascites

Not suitable:

• Severe renal insufficiency (GFR below 30 ml/min)
• Severe hyperkalemia
• Addison's disease
• Anuria
• At the same time as eplerenone

Heart failure:

• 25-50 mg once daily
• If potassium is below 5.0 mmol/l: 25 mg
• If potassium is above 5.5 mmol/l: reduce the dose or pause treatment

Treatment-resistant high blood pressure:

• 25-50 mg once daily

Liver cirrhosis with ascites:

• Starting dose: 100 mg daily
• Can be increased up to 400 mg daily
• In combination with furosemide (ratio 100:40)

Primary hyperaldosteronism:

• 100-400 mg daily

Available strengths:

• 25 mg, 50 mg, 100 mg tablets

How to take:

• Once daily, preferably in the morning or at midday
• With or after meals (improved absorption)
• With sufficient water

Important notes:

• Close monitoring of potassium (potassium can rise dangerously!)
• No potassium supplements without medical instruction
• No potassium-containing salt substitutes
• Have your kidney function checked regularly
• If potassium is above 5.5 mmol/l: contact a doctor immediately

Monitoring:

• Potassium and creatinine: after 1 week, 4 weeks, then every 3 months
• In heart failure: more frequent monitoring

Spironolactone must not be taken in case of:

• Severe hyperkalemia (above 5.5 mmol/l)
• Severe renal insufficiency (GFR below 30 ml/min)
• Addison's disease (adrenal insufficiency)
• Anuria
• At the same time as eplerenone
• Hypersensitivity to spironolactone

Caution in case of:

• Moderate renal insufficiency (close potassium monitoring)
• Concomitant use of ACE inhibitors/sartans (risk of hyperkalemia!)
• Diabetes mellitus (increased risk of hyperkalemia)
• Concomitant use of NSAIDs
• Elderly patients

Pregnancy and breastfeeding: Contraindicated throughout pregnancy and during breastfeeding. The antiandrogenic effect can disrupt the development of male fetuses.

Common (1-10%):

• Hyperkalemia (most important side effect!)
• Gynecomastia in men (dose-dependent, up to 10%)
• Breast tension and tenderness
• Gastrointestinal complaints
• Fatigue, drowsiness
• Headache

Uncommon (0.1-1%):

• Menstrual disorders in women
• Mood changes in women
• Erectile dysfunction in men
• Skin rash
• Nausea, vomiting
• Muscle cramps

Rare:

• Severe hyperkalemia (life-threatening!)
• Hyponatremia
• Metabolic acidosis
• Elevated liver function tests
• Changes in blood count

Gynecomastia: Breast enlargement in men is dose-dependent and reversible after discontinuation. Alternative in case of intolerance: eplerenone (more selective, less antiandrogenic).

Dangerous combinations (risk of hyperkalemia!):

• ACE inhibitors and sartans → close potassium monitoring!
• Potassium supplements → contraindicated
• Other potassium-sparing diuretics (triamterene, amiloride) → contraindicated
• Eplerenone → contraindicated
• Trimethoprim → intensified hyperkalemia

Caution with:

• NSAIDs → reduced diuresis, hyperkalemia
• Lithium → increased lithium levels
• Digoxin → increased digoxin levels
• Antihypertensives → enhanced lowering of blood pressure

Important: The combination of spironolactone with ACE inhibitors/sartans is standard in heart failure, but requires close potassium monitoring. The risk of severe hyperkalemia is real!