Spironolactone Dosing for Heart Failure
For adults with heart failure and reduced ejection fraction (HFrEF), initiate spironolactone at 25 mg once daily in patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m², with a target dose of 50 mg once daily. 1
Patient Selection Criteria
Spironolactone is indicated for patients meeting ALL of the following criteria:
- LVEF ≤35-40% 2
- Moderate to severe symptoms (NYHA functional class III-IV) 2
- Already on optimal doses of ACE inhibitor (or ARB) AND beta-blocker 2
- Adequate renal function and normal serum potassium 2
The landmark RALES trial demonstrated a 30% reduction in mortality (relative risk 0.70, P<0.001) and 35% reduction in heart failure hospitalizations when spironolactone was added to standard therapy 3. Both progressive heart failure deaths and sudden cardiac deaths were reduced 2, 3.
Initiation Protocol
Pre-Treatment Requirements
Before starting spironolactone, verify: 2
Starting Dose
- Standard dose: 25 mg once daily 2, 1
- Alternative: 12.5 mg daily or 25 mg every other day for patients at higher risk of hyperkalemia 2
- For eGFR 30-50 mL/min/1.73 m²: Consider 25 mg every other day 1
Stop all potassium supplementation when initiating spironolactone 2. Counsel patients to avoid high-potassium foods and NSAIDs 2.
Monitoring Schedule
Initial Phase
Critical monitoring timeline: 2
- 3 days after initiation: Check potassium and creatinine 2
- 1 week after initiation: Recheck potassium and creatinine 2
- 4 weeks after initiation: Recheck before considering dose increase 2
Dose Titration
After 4-8 weeks, if tolerating 25 mg daily well: 2, 1
- Increase to target dose of 50 mg once daily 2, 1
- Recheck potassium and creatinine at 1 and 4 weeks after dose increase 2
Maintenance Monitoring
Once stable on maintenance dose: 2
- Check potassium and creatinine at 1,2,3, and 6 months 2
- Then every 6 months thereafter 2
- Monthly for first 3 months minimum 2
Managing Adverse Effects
Hyperkalemia Management
If potassium rises to >5.5 mEq/L: 2
If potassium rises to ≥6.0 mEq/L: 2
Worsening Renal Function
If creatinine rises to >220 μmol/L (2.5 mg/dL): 2
- Halve the dose to 25 mg every other day 2
If creatinine rises to >310 μmol/L (3.5 mg/dL): 2
- Stop spironolactone immediately 2
Gynecomastia
Occurs in approximately 10% of men on spironolactone 2, 3. If painful gynecomastia or breast enlargement develops, switch to eplerenone (25-50 mg daily), which has significantly lower rates of this side effect 2, 4.
Critical Safety Warnings
Real-World Hyperkalemia Risk
The risk of hyperkalemia in clinical practice substantially exceeds that seen in trials. After RALES publication, population-based data from Ontario showed hospitalizations for hyperkalemia increased from 2.4 to 11 per 1000 patients, with associated mortality rising from 0.3 to 2 per 1000 2. This occurred as spironolactone prescriptions tripled in the general heart failure population 2.
Contraindicated Combinations
Avoid the routine triple combination of ACE inhibitor + ARB + aldosterone antagonist due to excessive hyperkalemia risk 2. The combination of two RAS blockers with spironolactone is particularly dangerous 2.
Special Circumstances
Instruct patients to temporarily stop spironolactone during: 2
These volume-depleting conditions markedly increase hyperkalemia risk 2.
Dosing Considerations
Spironolactone can be taken with or without food, but should be taken consistently 1. The FDA-approved oral suspension formulation (CaroSpir®, 25 mg/5 mL) is available for patients with swallowing difficulties 5.
For resistant hypertension (off-label for this question but relevant context), the dose range is 25-100 mg daily 2, 6, but for heart failure the evidence-based target remains 50 mg once daily 2, 1.