What is the appropriate dosage and usage of Spironolactone (an aldosterone antagonist) for patients with various medical conditions, including heart failure, hypertension, edema, primary aldosteronism, and polycystic ovary syndrome (PCOS)?

Spironolactone Dosing and Usage

Start spironolactone at 25 mg once daily for heart failure with reduced ejection fraction (LVEF ≤35-40%) in patients with NYHA class II-IV symptoms, targeting a maintenance dose of 50 mg once daily after 4 weeks if potassium remains ≤5.0 mEq/L and renal function is stable. 1, 2, 3

Heart Failure with Reduced Ejection Fraction (Primary Indication)

Patient Selection Criteria

• LVEF ≤35-40% with NYHA class II-IV symptoms 1
• For NYHA class II patients, require either prior cardiovascular hospitalization or elevated natriuretic peptide levels 1
• Baseline requirements before initiation: 1, 4
  • Serum potassium <5.0 mEq/L
  • Creatinine ≤2.5 mg/dL in men or ≤2.0 mg/dL in women
  • eGFR >30 mL/min/1.73 m²
• Patients must already be on optimal doses of beta-blocker and ACE inhibitor or ARB (but never combine ACE inhibitor + ARB + spironolactone due to severe hyperkalemia risk) 1, 2, 5

Dosing Protocol for Heart Failure

Initial Dosing: 1, 3, 4

• eGFR >50 mL/min/1.73 m²: Start 25 mg once daily
• eGFR 30-50 mL/min/1.73 m²: Start 12.5-25 mg once daily or 25 mg every other day 1, 2, 3

Dose Titration: 1, 3

• After 4-8 weeks, increase to target dose of 50 mg once daily if potassium ≤5.0 mEq/L and no worsening renal function
• Do not exceed 50 mg daily in heart failure - higher doses increase hyperkalemia risk without proven additional benefit 2

Critical Monitoring Schedule: 1, 3

• Check potassium and creatinine at 2-3 days, 7 days, 1 week, and 4 weeks after initiation
• Then monthly for 3 months, followed by every 3 months thereafter
• Restart monitoring cycle with any ACE inhibitor/ARB dose changes 1

Management of Complications

Hyperkalemia Management: 1

• Potassium 5.5-6.0 mEq/L: Halve dose to 25 mg every other day
• Potassium ≥6.0 mEq/L: Stop immediately and monitor closely

Worsening Renal Function: 1

• Creatinine rises to 220 µmol/L (2.5 mg/dL): Halve dose to 25 mg every other day
• Creatinine >310 µmol/L (3.5 mg/dL): Stop immediately

Gynecomastia (occurs in 10-21% of men): 1, 5

• Switch to eplerenone 50 mg once daily (equivalent to spironolactone 25 mg)

Essential Hypertension

Dosing: 2, 4, 6

• Initial: 25-100 mg once daily (single or divided doses)
• Titrate at 2-week intervals based on response
• Maximum effective dose: 100 mg/day - doses above this provide no additional blood pressure reduction 2, 4

The evidence shows spironolactone reduces systolic BP by approximately 20 mmHg and diastolic BP by 7 mmHg at doses of 100-500 mg/day, with no clear dose-response beyond 50-100 mg/day 6. A 25 mg/day dose may be insufficient for hypertension control 6.

Edema (Including Cirrhosis)

Dosing: 4

• Initial: 100 mg once daily (range 25-200 mg/day)
• Maximum: 200 mg/day 2
• For cirrhosis patients, initiate in hospital setting and titrate slowly 4
• When used as sole diuretic, administer for at least 5 days before increasing dose 4

Primary Hyperaldosteronism

Dosing: 2, 4

• 100-400 mg daily in preparation for surgery
• For patients unsuitable for surgery, use lowest effective dose for long-term maintenance 4

Post-Myocardial Infarction

Patient Selection: 1

• LVEF ≤40% with HF symptoms or diabetes history within 3-14 days post-MI

Dosing: 1

• Follow same heart failure dosing protocol (start 25 mg daily, target 50 mg daily)

Critical Safety Precautions

Mandatory Actions at Initiation: 1, 3

• Discontinue potassium supplements (or reduce significantly if history of hypokalemia)
• Counsel patients to avoid high-potassium foods and NSAIDs
• Verify baseline potassium <5.0 mEq/L and adequate renal function

Absolute Contraindications: 1, 5

• eGFR <30 mL/min/1.73 m²
• Baseline potassium >5.0 mEq/L
• Creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women)

Drug Interactions to Avoid: 2, 5, 3

• Never use triple therapy (ACE inhibitor + ARB + spironolactone) - markedly increased hyperkalemia risk
• Avoid NSAIDs
• Minimize potassium supplementation

Administration Considerations

• Can be taken with or without food, but maintain consistency 4
• For patients unable to swallow tablets, liquid suspension formulation (25 mg/5 mL) is available 7

Polycystic Ovary Syndrome (Off-Label)

Limited evidence supports spironolactone 200 mg/day for hirsutism in PCOS 8, though this is not a primary FDA-approved indication and requires careful monitoring given the high dose.