What is the recommended dosage and management of Spironolactone (potassium-sparing diuretic) for patients with heart failure or resistant hypertension?

Spironolactone Dosing and Management in Heart Failure and Resistant Hypertension

Heart Failure

For patients with NYHA class III-IV heart failure and reduced ejection fraction, start spironolactone at 25 mg once daily (or every other day if eGFR 30-50 mL/min/1.73m²), with a target dose of 25-50 mg once daily, added to ACE inhibitors and beta-blockers as second-line therapy. 1, 2

Initiation Requirements

• Baseline potassium must be ≤5.0 mEq/L 2
• eGFR must be >30 mL/min/1.73m² 1, 2
• Patient should be on background ACE inhibitor and beta-blocker therapy 1
• Avoid in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) 3, 4

Dosing Algorithm

• Standard starting dose: 25 mg once daily for patients with eGFR >50 mL/min/1.73m² 1, 2
• Reduced renal function (eGFR 30-50 mL/min/1.73m²): Start at 25 mg every other day 2
• Dose escalation: If tolerated after 4-8 weeks, may increase to 50 mg once daily 1, 2
• Maximum dose: 50 mg once daily for heart failure (though higher doses of 50-200 mg have been used safely in advanced NYHA class III/IV patients requiring natriuresis) 1, 5

Monitoring Protocol

Intensive early monitoring is critical to prevent life-threatening hyperkalemia:

• Check potassium and creatinine at 1,4,8, and 12 weeks after initiation 1
• Then at 6,9, and 12 months 1
• Subsequently every 6 months 1
• Reinitiate monitoring cycle if ACE inhibitor or ARB doses are changed 3

Management of Hyperkalemia

• Potassium 5.5-6.0 mmol/L: Reduce dose to 25 mg every other day and monitor closely 1
• Potassium >6.0 mmol/L: Stop spironolactone immediately and seek specialist advice 1, 3, 4
• Creatinine rises to >221 µmol/L (2.5 mg/dL): Reduce dose or discontinue 1

Clinical Benefits

The RALES study demonstrated that low-dose spironolactone (25 mg) added to standard therapy increased survival, reduced hospital admissions, and improved NYHA class in patients with severe heart failure 1. This mortality benefit establishes spironolactone as essential second-line therapy after ACE inhibitors and beta-blockers 1.

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Resistant Hypertension

For resistant hypertension (uncontrolled on ≥3 antihypertensive drugs at optimal doses), add spironolactone 25 mg once daily, with potential titration to 50 mg once daily after 2 weeks if blood pressure remains uncontrolled. 2, 6, 7

Dosing for Hypertension

• Starting dose: 25-100 mg once daily or in divided doses 2
• Typical effective dose: 25-50 mg once daily 3, 7
• Titration interval: Every 2 weeks 2
• Maximum dose: 100 mg/day (doses above this rarely provide additional blood pressure reduction) 2

Expected Blood Pressure Response

Spironolactone produces substantial blood pressure reductions in resistant hypertension:

• Average reduction of 22/10 mmHg across multiple trials 6
• At 1 month: 16.6/7.0 mmHg reduction 7
• At 6 months: 26.0/10.7 mmHg reduction 7

Monitoring in Hypertension

• Check potassium and creatinine before initiation 3
• Recheck at 1 and 4 weeks after starting 3
• Continue monitoring at 1,2,3, and 6 months, then every 6 months 3

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Critical Drug Interactions and Contraindications

Avoid Concomitant Use With:

• Other potassium-sparing diuretics (amiloride, triamterene) 1
• Potassium supplements 1
• NSAIDs (increase hyperkalemia risk and reduce efficacy) 1
• "Low salt" substitutes with high potassium content 1

Use Caution With:

• ACE inhibitors and ARBs (monitor potassium closely but combination is standard in heart failure) 1

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Common Adverse Effects

Gynecomastia and Breast Tenderness

• Occurs in approximately 10% of male patients 3, 4
• May require switching to eplerenone (2:1 conversion ratio: 50 mg eplerenone = 25 mg spironolactone) 4

Hyperkalemia

• Most serious adverse effect requiring vigilant monitoring 1, 6, 7
• Occurred in 4.1% of resistant hypertension patients requiring discontinuation 7

Renal Function Deterioration

• Monitor creatinine alongside potassium 1, 5
• May require dose reduction or discontinuation 1

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Special Clinical Situations

Patient Instructions

• Take consistently with or without food 2
• Temporarily stop spironolactone if diarrhea/vomiting occurs and contact physician 1
• Avoid over-the-counter NSAIDs (e.g., ibuprofen) 1
• Symptom improvement occurs within weeks to months 1

Cirrhosis with Ascites

• Initiate in hospital setting with slow titration 2
• Starting dose: 100 mg once daily (may range 25-200 mg) 2
• Administer for at least 5 days before increasing dose 2