What is the proper use and dosage of Spironolactone (aldosterone antagonist) for treating conditions like hypertension and heart failure?

Spironolactone: Proper Use and Dosing

For heart failure with reduced ejection fraction (LVEF ≤35-40%) and NYHA class III-IV symptoms, start spironolactone at 25 mg once daily and titrate to a target dose of 50 mg once daily, with mandatory serial monitoring of potassium and creatinine. 1

Indications for Spironolactone

Heart Failure (Primary Indication)

• LVEF ≤35% 1
• Moderate to severe symptoms (NYHA class III-IV) 1
• Already on optimal doses of beta-blocker AND ACE inhibitor or ARB (but NOT both ACE inhibitor and ARB together) 1
• Spironolactone reduces all-cause mortality by 30% and hospitalizations for heart failure by 35% when added to standard therapy 1, 2

Hypertension

• Resistant hypertension: Effective when blood pressure remains uncontrolled on ≥3 antihypertensive medications at optimal doses 2, 3, 4
• Dose range: 25-100 mg daily; doses >100 mg/day generally provide no additional blood pressure reduction 2

Other Indications

• Primary hyperaldosteronism: 100-400 mg daily 2
• Edema in cirrhosis: 100 mg daily (range 25-200 mg), initiated in hospital setting with slow titration 2

Dosing Protocol for Heart Failure

Initiation

• Check baseline renal function and serum potassium before starting 1, 5
• Starting dose: 25 mg once daily 1, 2
• For patients with eGFR 30-50 mL/min/1.73 m²: Consider 25 mg every other day to minimize hyperkalemia risk 5, 2
• Recheck potassium and creatinine at 1 and 4 weeks after initiation 1, 5

Dose Titration

• Consider increasing dose after 4-8 weeks if no adverse effects 1
• Target dose: 50 mg once daily 1, 5
• Recheck potassium and creatinine 1 and 4 weeks after each dose increase 1
• Do NOT increase dose if worsening renal function or hyperkalemia develops 1

Long-term Monitoring

• Check potassium and creatinine at 1,2,3, and 6 months after achieving maintenance dose 1, 5
• Then monitor every 6 months thereafter 1, 5
• After any dose changes, recheck within 2-3 days and again at 7 days 5

Managing Adverse Effects

Hyperkalemia (Most Critical Concern)

• Potassium 5.5-6.0 mmol/L: Halve the dose (e.g., 25 mg every other day) and monitor closely 1, 5
• Potassium ≥6.0 mmol/L: Stop spironolactone immediately and monitor closely; specific treatment may be needed 1, 5
• Hyperkalemia was uncommon in clinical trials but occurs more frequently in real-world practice, especially in elderly patients 1

Worsening Renal Function

• Creatinine >220 μmol/L (2.5 mg/dL): Halve the dose and monitor closely 1
• Creatinine >310 μmol/L (3.5 mg/dL): Stop spironolactone immediately and monitor closely 1

Gynecomastia

• Occurs in 10% of men on spironolactone 1
• If painful gynecomastia develops: Switch to eplerenone (25-50 mg once daily), which has lower affinity for androgen receptors 1

Critical Safety Considerations

Prerequisites for Starting Therapy

• Adequate renal function required 1
• Normal serum potassium required 1
• Avoid in patients with baseline potassium >5.0 mEq/L 5, 2

Drug Interactions to Avoid

• Do NOT combine with both ACE inhibitor AND ARB simultaneously 1
• Avoid concomitant use with: Potassium supplements, NSAIDs, high-potassium salt substitutes, other potassium-sparing diuretics 5

Patient Instructions

• Take consistently with respect to food (with or without, but same each time) 2
• Temporarily stop during diarrhea or vomiting and contact physician 5
• Watch for signs of hyperkalemia: Weakness, fatigue, paresthesias 5

Clinical Evidence Supporting Use

Heart Failure Mortality Benefit

• The RALES trial demonstrated a 30% reduction in all-cause mortality and 35% reduction in heart failure hospitalizations 1, 2
• Number needed to treat: 9 patients for 2 years to prevent 1 death 1
• Benefits were additional to those from ACE inhibitors, diuretics, and digoxin 1, 2

Resistant Hypertension

• Average blood pressure reduction of 22/10 mmHg when added to resistant hypertension regimens 4
• Effective across multiple studies in patients uncontrolled on ≥3 medications 3, 4

Common Pitfalls to Avoid

• Do not use in patients with inadequate renal function or elevated baseline potassium 1
• Do not skip the mandatory serial monitoring schedule—hyperkalemia risk is highest in real-world practice versus clinical trials 1
• Do not combine with triple RAAS blockade (ACE inhibitor + ARB + spironolactone) 1
• Do not use doses >100 mg/day for hypertension—no additional benefit 2