What is the recommended dosage and usage of Spironolactone (aldosterone antagonist) for treating conditions like heart failure, hypertension, and edema?

Spironolactone Dosing and Usage

For heart failure with reduced ejection fraction, start spironolactone at 25 mg once daily (or 12.5-25 mg if borderline renal function) and titrate to the target dose of 50 mg once daily after 4-8 weeks if potassium remains ≤5.0 mEq/L and renal function is stable. 1, 2, 3

Heart Failure with Reduced Ejection Fraction (HFrEF)

Patient Selection and Initiation

• Spironolactone is indicated as second-line therapy for NYHA class III/IV heart failure patients who remain symptomatic despite ACE inhibitors and beta-blockers. 4
• Only initiate if serum potassium is ≤5.0 mEq/L and eGFR >30 mL/min/1.73m². 2, 3
• Discontinue potassium supplements before starting spironolactone. 1, 2

Dosing Algorithm by Renal Function

For eGFR >50 mL/min/1.73m²:

• Start at 25 mg once daily 2, 3
• Increase to target dose of 50 mg once daily after 4 weeks if potassium ≤5.0 mEq/L and renal function stable 1, 2
• Do not exceed 50 mg/day in heart failure—higher doses increase hyperkalemia risk without proven additional benefit. 1

For eGFR 30-50 mL/min/1.73m²:

• Start at 12.5-25 mg once daily or consider 25 mg every other day 1, 2, 3
• Maintain at 12.5-25 mg once daily as the target dose 2
• Doses greater than 25 mg/day are not recommended with borderline renal function. 1

For eGFR <30 mL/min/1.73m²:

• Spironolactone is generally contraindicated 3

Critical Monitoring Requirements

• Check potassium and creatinine within 2-3 days after initiation, then again at 7 days. 2
• Continue monthly monitoring for the first 3 months, then every 3 months thereafter. 2
• If potassium rises to 5.0-5.5 mEq/L: reduce dose to 25 mg every other day 3
• If potassium >5.5 mEq/L or creatinine increases >30-50% from baseline: discontinue spironolactone 5

Important Safety Warnings

• Avoid the routine triple combination of ACE inhibitor + ARB + spironolactone due to markedly increased hyperkalemia risk. 1, 2
• Counsel patients to avoid high-potassium foods and NSAIDs. 2
• Gynecomastia occurs in approximately 5% of males; consider switching to eplerenone if this develops 6, 5
• Real-world discontinuation rates reach 25-30% due to hyperkalemia, renal dysfunction, or gynecomastia—significantly higher than clinical trial rates. 5, 7

Essential Hypertension

Dosing Strategy

• Start at 25-100 mg once daily, administered as single or divided doses. 3
• Titrate at 2-week intervals based on blood pressure response 3
• Maximum practical dose is 100 mg/day—doses above this do not provide additional blood pressure reduction. 1, 3

Edema (Including Cirrhosis)

Dosing Approach

• For cirrhotic patients, initiate therapy in a hospital setting and titrate slowly. 3
• Start at 100 mg daily (single or divided doses), with a range of 25-200 mg daily 3
• Maximum dose for edema is 200 mg/day. 1
• When used as sole diuretic agent, administer for at least 5 days before increasing dose 3

Primary Hyperaldosteronism

Dosing Range

• Administer 100-400 mg daily for preoperative preparation or long-term maintenance in patients unsuitable for surgery. 1, 3, 8
• Use the lowest effective dose for long-term maintenance therapy 3

Administration Considerations

• Spironolactone can be taken with or without food, but should be taken consistently with respect to food. 3
• The medication is extensively metabolized by the liver, with therapeutic effects attributable to the active metabolite canrenone 8

Alternative: Eplerenone

• For patients who cannot tolerate spironolactone (particularly due to gynecomastia), eplerenone is an alternative with similar efficacy but greater mineralocorticoid receptor selectivity. 2, 6
• Eplerenone dosing: start at 25 mg once daily, titrate to 50 mg once daily within 4 weeks 6
• Eplerenone has significantly lower rates of anti-androgenic side effects (gynecomastia, menstrual irregularities) 6, 8

Key Clinical Pitfall

The most dangerous error is inadequate monitoring for hyperkalemia, which occurs more frequently in real-world practice than in clinical trials. 5 Even in carefully selected patients receiving higher doses (50-200 mg) for advanced heart failure, discontinuation rates due to hyperkalemia or renal dysfunction can reach 17-30% 5, 9. When spironolactone must be discontinued, this is associated with a 2-4 fold higher risk of subsequent cardiovascular events, so maintaining patients on even low doses (15-25 mg) is preferable to complete discontinuation. 7