Spironolactone Dosing Recommendations
For heart failure, spironolactone should be initiated at 12.5 to 25 mg once daily and may be titrated up to a maximum of 50 mg daily, with careful monitoring of potassium and renal function. 1
Heart Failure Dosing Protocol
Initial Dosing
- For patients with eGFR ≥50 mL/min/1.73m² and serum K+ ≤5.0 mEq/L: Start with 12.5-25 mg once daily 1, 2
- For patients with eGFR 30-49 mL/min/1.73m²: Start with 12.5 mg once daily or 25 mg every other day 1
- Contraindicated if:
- Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women
- eGFR <30 mL/min/1.73m²
- Serum potassium >5.0 mEq/L 1
Maintenance Dosing
- After 4 weeks, if K+ remains ≤5.0 mEq/L:
- For eGFR ≥50 mL/min/1.73m²: May increase to 25 mg once or twice daily (maximum 50 mg daily)
- For eGFR 30-49 mL/min/1.73m²: May increase to 12.5-25 mg once daily 1
Monitoring Requirements
- Check potassium and renal function:
- 2-3 days after initiation
- 7 days after initiation
- Monthly for first 3 months
- Every 3 months thereafter 1
- Additional monitoring when:
- Dose is increased
- ACE inhibitors or ARBs are added or increased
- Patient experiences dehydration or volume depletion 1
Dosing for Other Indications
Hypertension
- Initial dose: 25-100 mg daily (single or divided doses)
- Titrate at 2-week intervals
- Maximum effective dose: 100 mg daily (higher doses generally don't provide additional blood pressure reduction) 2, 3
Edema in Cirrhosis
- Initial dose: 100 mg daily (range 25-200 mg)
- For patients with concerns of hyperkalemia: 12.5-25 mg daily 1
- Maintenance: 50-100 mg daily, titrated based on response 1
Primary Hyperaldosteronism
- 100-400 mg daily for preoperative management
- For long-term maintenance: lowest effective dose 2
Special Considerations and Pitfalls
Risk Factors for Hyperkalemia
- Concomitant ACE inhibitor or ARB therapy
- Renal insufficiency (serum creatinine >1.6 mg/dL)
- Diabetes mellitus
- Advanced age
- Dehydration or worsening heart failure
- Use of other medications that can cause hyperkalemia 4
Management Strategies to Minimize Hyperkalemia
- Discontinue potassium supplements when initiating spironolactone
- Counsel patients to avoid high-potassium foods and NSAIDs
- Use lower doses (12.5-25 mg daily) when combined with ACE inhibitors 5
- Hold spironolactone if K+ ≥5.5 mEq/L or worsening renal function
- Consider restarting at reduced dose after resolution of hyperkalemia 1
Side Effects
- Gynecomastia and breast tenderness in men (10% of patients)
- For patients with gynecomastia, consider switching to eplerenone 1
- Menstrual irregularities in women
- Hyperkalemia (risk increases with doses >25 mg daily) 5
The evidence strongly suggests that doses of 12.5-25 mg daily are effective for heart failure while minimizing risk of hyperkalemia, especially when combined with ACE inhibitors 5. Higher doses (50-75 mg) are associated with significantly increased risk of hyperkalemia (20-24% incidence) compared to lower doses (5-13% incidence) 5.