What is the recommended dosage and usage of Spironolactone (aldosterone antagonist) for treating conditions like heart failure, hypertension, and edema?

Spironolactone Dosage and Usage Guidelines for Heart Failure, Hypertension, and Edema

For heart failure, spironolactone should be initiated at 25 mg once daily with a target dose of 50 mg once daily in patients with normal renal function and serum potassium ≤5.0 mEq/L. 1

Heart Failure Dosing

• Start with 25 mg once daily in patients with eGFR >50 mL/min/1.73m² and serum potassium ≤5.0 mEq/L 1, 2
• For patients with eGFR between 30-50 mL/min/1.73m², start with 25 mg every other day or 12.5 mg daily due to increased risk of hyperkalemia 1
• Consider dose up-titration after 4-8 weeks to target dose of 50 mg once daily if no worsening renal function or hyperkalemia 1
• Spironolactone is indicated for patients with LVEF ≤35% and moderate to severe symptoms (NYHA class III-IV) 1
• Patients should be on optimal doses of beta-blockers and ACE inhibitors or ARBs (but not both ACE inhibitors and ARBs) 1

Hypertension Dosing

• Initial daily dose of 25-100 mg administered in single or divided doses 2
• Titrate at two-week intervals as needed 2
• Maximum dose of 100 mg/day as higher doses generally do not provide additional blood pressure reduction 2, 3
• Particularly effective for resistant hypertension as a fourth-line agent, with mean BP reduction of 21.9/9.5 mmHg when added to existing regimens 4

Edema Management

• For edema in cirrhosis: initial dose of 100 mg daily (range 25-200 mg daily) 2
• Initiate therapy in hospital setting for cirrhotic patients and titrate slowly 2
• When used as sole diuretic agent, administer for at least 5 days before increasing dose 2

Monitoring Requirements

• Check renal function and serum electrolytes before starting treatment 1
• Recheck renal function and electrolytes at 1 and 4 weeks after initiation 1
• After achieving maintenance dose, monitor at 1,2,3, and 6 months, then every 6 months thereafter 1
• Discontinue potassium supplements when starting spironolactone 1
• Counsel patients to avoid high-potassium foods and NSAIDs 1

Dose Adjustments for Adverse Effects

• If potassium rises to >5.5 mmol/L, halve the dose (e.g., to 25 mg on alternate days) 1
• If potassium rises to ≥6.0 mmol/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

Common Side Effects and Management

• Gynecomastia or breast discomfort occurs in approximately 10% of male patients 1, 4
• For men with breast discomfort/enlargement, consider switching to eplerenone 1
• Hyperkalemia risk is higher in elderly patients, those with renal dysfunction, and when combined with high-dose ACE inhibitors 1
• In patients unable to tolerate target doses, a low-dose strategy (12.5-25 mg) is preferable to discontinuation 5

Important Caveats

• Spironolactone should not be used in patients with serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 1
• Avoid use in patients with baseline potassium >5.0 mEq/L 1
• The combination of ACE inhibitor, ARB, and aldosterone antagonist should be avoided due to high risk of hyperkalemia 1
• Even at lower than target doses (around 20 mg/day), spironolactone may still provide clinical benefit in high-risk patients 5
• For primary hyperaldosteronism, higher doses (100-400 mg daily) may be required 2, 6