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

Spironolactone Dosage and Management in Heart Failure and Resistant Hypertension

For heart failure patients, spironolactone should be initiated at 25 mg once daily (or 12.5 mg in renal impairment) with a target dose of 25-50 mg daily, while for resistant hypertension, doses of 25-100 mg daily are recommended with careful monitoring of potassium and renal function. 1, 2

Dosing for Heart Failure

Initial Dosing

• For patients with heart failure and LVEF ≤35% with NYHA class III-IV symptoms, start spironolactone at 25 mg once daily if serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73m² 1
• For patients with moderate renal impairment (eGFR 30-49 mL/min/1.73m²), start with 12.5-25 mg once daily or 25 mg every other day 1, 2
• Avoid spironolactone in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) or baseline potassium >5.0 mEq/L 1

Maintenance Dosing

• After 4-8 weeks, consider uptitration to target dose of 25-50 mg once daily if potassium and renal function remain stable 1
• If potassium rises to 5.5-6.0 mmol/L or creatinine increases to >220 μmol/L (2.5 mg/dL), reduce dose to 25 mg on alternate days 1
• If potassium exceeds 6.0 mmol/L or creatinine rises to >310 μmol/L (3.5 mg/dL), stop spironolactone immediately 1

Dosing for Resistant Hypertension

• Initial dose of 25 mg daily, which can be titrated up to 100 mg daily 2, 3
• Doses greater than 100 mg/day generally do not provide additional blood pressure reduction 2
• Average blood pressure reduction with spironolactone in resistant hypertension is approximately 22/10 mmHg 3, 4

Monitoring Protocol

Initial Monitoring

• Check renal function and serum electrolytes before starting treatment 1
• Recheck at 1 week and 4 weeks after initiation 1, 5
• Further monitoring at 8 and 12 weeks after starting treatment 1

Long-term Monitoring

• Once on maintenance dose, check at 1,2,3, and 6 months, then every 6 months thereafter 1
• More frequent monitoring is needed in patients with risk factors for hyperkalemia or renal dysfunction 1, 5
• After any dose increase, restart the monitoring cycle (1 week and 4 weeks) 1

Special Considerations

Risk Factors for Adverse Effects

• Concomitant use of ACE inhibitors, ARBs, NSAIDs, or potassium supplements increases risk of hyperkalemia 1, 5
• Elderly patients and those with baseline renal dysfunction are at higher risk for hyperkalemia 5
• Male patients may develop gynecomastia (10% incidence) with spironolactone 1, 4

Management of Adverse Effects

• If gynecomastia develops, consider switching to eplerenone (50 mg eplerenone ≈ 25 mg spironolactone) 1, 6
• Temporarily discontinue spironolactone during episodes of diarrhea, vomiting, or dehydration 1, 5
• Advise patients to avoid high-potassium foods and over-the-counter NSAIDs 1

Common Pitfalls to Avoid

• Underestimating hyperkalemia risk in real-world settings (up to 24% incidence vs. 2% in clinical trials) 1, 5
• Failure to discontinue potassium supplements when initiating spironolactone 1, 5
• Routine triple combination of ACEIs, ARBs, and spironolactone should be avoided due to high hyperkalemia risk 1
• Inadequate monitoring of potassium and renal function, especially in the first few months of treatment 1, 5

Evidence-Based Patient Selection

• For heart failure: LVEF ≤35% with NYHA class III-IV symptoms despite optimal therapy with ACEIs/ARBs and beta-blockers 1
• For resistant hypertension: Uncontrolled BP despite ≥3 antihypertensive medications at optimal doses 3, 4
• Secondary causes of hypertension should be ruled out before labeling as resistant hypertension 3