Spironolactone Dosing and Monitoring Protocol for Heart Failure and Resistant Hypertension
For patients with heart failure or resistant hypertension, spironolactone should be initiated at 25 mg once daily with a target dose of 50 mg once daily, accompanied by careful monitoring of renal function and serum potassium. 1, 2
Indications for Spironolactone
Heart Failure
- Indicated for patients with LVEF ≤35% and moderate to severe symptoms (NYHA class III-IV) 1
- Should be added to optimal therapy with beta-blockers and either ACE inhibitors or ARBs (but not both) 1
- Reduces mortality by 30% and hospitalization for worsening heart failure by 35% 1
Resistant Hypertension
- Effective add-on therapy for patients with hypertension uncontrolled on ≥3 antihypertensive medications 3, 4
- Can reduce blood pressure by an average of 22/10 mmHg in resistant hypertension 3, 5
Dosing Protocol
Initial Assessment Before Starting Therapy
- Check renal function and serum electrolytes 1
- Ensure serum potassium is ≤5.0 mEq/L 1
- Verify creatinine is ≤2.5 mg/dL in men or ≤2.0 mg/dL in women (or eGFR >30 mL/min/1.73 m²) 1, 6
Starting Dose
- For heart failure with eGFR >50 mL/min/1.73 m²: 25 mg once daily 1, 6
- For heart failure with eGFR 30-50 mL/min/1.73 m²: 25 mg every other day 1, 6
- For resistant hypertension: 25 mg once daily 3, 5
Dose Titration
- Consider dose up-titration after 4-8 weeks if no adverse effects 1, 2
- Target dose: 50 mg once daily for heart failure 1
- For resistant hypertension: may increase to 50 mg daily if needed 4, 5
- Do not increase dose if worsening renal function or hyperkalemia occurs 1
Monitoring Protocol
Early Monitoring
- Recheck renal function and serum electrolytes at 1 week and 4 weeks after starting treatment 1, 2
- If dose is increased, recheck labs 1 week and 4 weeks after the increase 1
Long-term Monitoring
- Check renal function and electrolytes at 1,2,3, and 6 months after achieving maintenance dose 1, 2
- Continue monitoring every 6 months thereafter 1, 2
- More frequent monitoring for high-risk patients (elderly, diabetics, renal impairment) 1
Management of Adverse Effects
Hyperkalemia
- If potassium rises to >5.5 mmol/L: halve the dose (e.g., to 25 mg every other day) 1
- If potassium rises to ≥6.0 mmol/L: stop spironolactone immediately 1
- Incidence of serious hyperkalemia in clinical practice may be higher (up to 24%) than in clinical trials (2-5%) 1
Worsening Renal Function
- If creatinine rises to >220 μmol/L (2.5 mg/dL): halve the dose 1
- If creatinine rises to >310 μmol/L (3.5 mg/dL): stop spironolactone immediately 1
Other Side Effects
- Gynecomastia or breast tenderness in men (occurs in approximately 10% of male patients) 1
- Consider switching to eplerenone if gynecomastia develops 1, 7
Important Precautions
- Discontinue potassium supplements when starting spironolactone 1
- Counsel patients to avoid high-potassium foods and NSAIDs 1
- Instruct patients to temporarily stop spironolactone during episodes of diarrhea, vomiting, or when loop diuretic therapy is interrupted 1, 2
- Avoid routine triple combination of ACE inhibitors, ARBs, and spironolactone due to increased risk of hyperkalemia 1
Special Populations
- For elderly patients or those with low muscle mass: use eGFR rather than serum creatinine alone to assess renal function 1
- For patients with cirrhosis: initiate therapy in hospital setting and titrate slowly 6
- For post-MI patients with LVEF ≤40% and heart failure: consider eplerenone as an alternative 1, 7