What is the typical starting dose of spironolactone (aldosterone antagonist) for patients?

Spironolactone Dosing Guidelines

The typical starting dose of spironolactone for most patients is 12.5 to 25 mg daily, with dose adjustments based on clinical indication, renal function, and potassium levels. 1

Dosing by Clinical Indication

Heart Failure

• For heart failure with reduced ejection fraction (HFrEF):
  • Initial dose: 12.5-25 mg once daily 1
  • Maintenance dose: Can be increased to 50 mg daily if tolerated 1
  • For patients with concerns about hyperkalemia or marginal renal function (eGFR 30-49 mL/min/1.73 m²), start with every-other-day dosing 1
  • FDA recommendation: For serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m², start at 25 mg once daily 2

Liver Cirrhosis with Ascites

• Initial dose: 50-100 mg daily 1
• Can be progressively increased up to 400 mg/day if needed 1
• Allow at least 72 hours between dose increases due to long half-life 1

Hypertension

• Initial dose: 25-100 mg daily, administered in single or divided doses 2
• Doses greater than 100 mg/day generally do not provide additional blood pressure reduction 2, 3

Monitoring and Dose Adjustments

Laboratory Monitoring

• Before starting: Check baseline potassium and renal function 1
• After initiation: Check potassium and renal function within 2-3 days and again at 7 days 1
• Maintenance monitoring: Monthly for first 3 months, then every 3 months thereafter 1

Dose Adjustments Based on Laboratory Results

• If potassium rises to >5.5 mEq/L: Halve the dose or switch to alternate-day dosing 1
• If potassium rises to ≥6.0 mEq/L: Stop spironolactone immediately 1
• 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

Special Populations

Elderly Patients

• Consider starting at lower doses (12.5 mg daily) in elderly patients 4
• Elderly patients are more prone to hyperkalemia, especially with renal impairment 4, 5
• In TOPCAT trial, elderly patients (≥75 years) received lower spironolactone doses (median ~20 mg/day) 5

Renal Impairment

• For eGFR 30-49 mL/min/1.73 m²: Consider 25 mg every other day 1, 2
• For eGFR <30 mL/min/1.73 m²: Spironolactone is generally contraindicated 1
• Patients with renal impairment have higher rates of hyperkalemia (67% vs 11% in those with normal renal function) 4

Risk Minimization Strategies

• Discontinue potassium supplements when initiating spironolactone 1
• Counsel patients to avoid high-potassium foods and NSAIDs 1
• Instruct patients to temporarily stop spironolactone during episodes of diarrhea, dehydration, or when loop diuretic therapy is interrupted 1
• Avoid routine triple combination of ACE inhibitor, ARB, and spironolactone 1

Common Side Effects

• Hyperkalemia (2-5% in clinical trials, up to 36% in real-world settings) 1
• Gynecomastia and breast pain (more common in men) 1
• Menstrual irregularities 6
• Dizziness, fatigue, and headache 1, 6

Clinical Pearls

• Lower doses (12.5-25 mg) are often as effective as higher doses with fewer side effects 7, 5
• In patients unable to tolerate target doses, a low-dose strategy is preferred to stopping treatment completely 5
• The full effect of dose changes may not be seen for up to 3 days due to spironolactone's long half-life 1, 6
• For patients with gynecomastia, consider switching to eplerenone 1