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

Spironolactone Dosage and Usage in Heart Failure and Resistant Hypertension

For heart failure patients, spironolactone should be initiated at 25 mg once daily with a target dose of 25-50 mg once daily, while for resistant hypertension, a starting dose of 25 mg with titration up to 100 mg daily is recommended. 1, 2

Heart Failure Dosing

Initial Dosing

• Start at 25 mg once daily in patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73m² 1, 2
• Consider 25 mg every other day in patients with eGFR between 30-50 mL/min/1.73m² due to increased hyperkalemia risk 2
• Spironolactone is indicated as second-line therapy (after ACE inhibitors and beta-blockers) in patients with NYHA class III-IV heart failure 1

Dose Titration and Target

• Target dose is 25-50 mg once daily 1
• If potassium rises to between 5.5-6.0 mmol/L or creatinine rises to 2.5 mg/dL, reduce dose to 25 mg on alternate days 1
• Patients who tolerate 25 mg daily may have dosage increased to 50 mg daily as clinically indicated 2

Monitoring

• Check blood chemistry at 1,4,8, and 12 weeks; then at 6,9, and 12 months; then every 6 months thereafter 1
• If potassium rises >6.0 mmol/L or significant rise in creatinine occurs, seek specialist advice 1
• Higher doses (50-200 mg) have been studied in advanced heart failure but require very careful monitoring 3

Resistant Hypertension Dosing

Initial Dosing and Titration

• Start with 25 mg daily 2, 4
• Dosage can be titrated at two-week intervals 2
• Effective dose range is 25-100 mg daily, with doses greater than 100 mg generally not providing additional blood pressure reduction 2, 4

Efficacy

• Low-dose spironolactone (25-50 mg) is highly effective for resistant hypertension, with average blood pressure reductions of 16.6/7.0 mm Hg at 1 month and 26.0/10.7 mm Hg at 6 months 4
• Studies consistently show average blood pressure lowering of approximately 22/10 mm Hg when added to existing regimens 5

Important Considerations for Both Indications

Drug Interactions to Monitor

• ACE inhibitors, angiotensin receptor blockers, other potassium-sparing diuretics 1
• Potassium supplements 1
• NSAIDs (patients should avoid self-purchased over-the-counter NSAIDs) 1
• 'Low salt' substitutes with high potassium content 1

Potential Adverse Effects

• Hyperkalemia (primary concern, but uncommon at recommended doses with proper monitoring) 1, 6
• Male patients may develop breast discomfort and/or gynecomastia (reported in 5.2% of males) 1, 4
• Renal insufficiency 5

Special Precautions

• Temporarily stop spironolactone if diarrhea and/or vomiting occur and contact physician 1
• For patients with resistant hypertension and chronic kidney disease, consider concomitant use of patiromer to reduce hyperkalemia risk and enable more persistent spironolactone use 7
• Can be taken with or without food, but should be taken consistently with respect to food 2

Clinical Pearls

• Spironolactone has been shown to increase survival, reduce hospital admissions, and improve NYHA class in severe heart failure patients 1
• Symptom improvement typically occurs within a few weeks to a few months of starting treatment 1
• With careful monitoring of plasma electrolytes, low-dose spironolactone is an effective add-in drug even in patients already on an angiotensin-blocking agent 6
• In heart failure patients, the RALES study demonstrated significant benefits with low-dose spironolactone added to standard therapy 1