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

Spironolactone Dosing and Usage

Heart Failure with Reduced Ejection Fraction

For heart failure, start spironolactone at 25 mg once daily (or 12.5-25 mg once daily if marginal renal function), and titrate to a target dose of 50 mg once daily after 4 weeks if potassium remains ≤5.0 mEq/L and renal function is stable. 1, 2, 3

Initial Dosing Strategy

• Start with 25 mg once daily if serum potassium is ≤5.0 mEq/L and eGFR >50 mL/min/1.73m² 2, 3
• For patients with eGFR 30-50 mL/min/1.73m², initiate at 25 mg every other day or 12.5 mg once daily to minimize hyperkalemia risk 1, 2, 3
• Do not initiate if potassium >5.0 mEq/L or eGFR <30 mL/min/1.73m² 2

Dose Titration

• Increase to 50 mg once daily after 4 weeks if potassium remains ≤5.0 mEq/L and renal function is stable 1, 2
• Do not exceed 50 mg daily in heart failure patients, as doses >50 mg/day increase hyperkalemia risk without proven additional clinical benefit 1
• For patients with eGFR 30-49 mL/min/1.73m², maintain at 12.5-25 mg once daily as the maximum dose 2

Monitoring Requirements

• Check potassium and creatinine within 2-3 days after initiation, then again at 7 days 2
• Recheck at 1,4,8, and 12 weeks after initiation 4
• Continue monitoring monthly for the first 3 months, then every 3 months thereafter 2

Dose Adjustment for Adverse Effects

• If potassium rises to 5.0-5.5 mEq/L: reduce dose by 50% 4
• If potassium rises to 5.5-6.0 mEq/L: reduce dose to 25 mg every other day 4
• If potassium >6.0 mEq/L: stop spironolactone immediately 4
• If creatinine rises >221 μmol/L (2.5 mg/dL): reduce dose and monitor closely 4

Critical Safety Precautions

• Discontinue all potassium supplements when initiating spironolactone 1, 2
• Avoid the triple combination of ACE inhibitors, ARBs, and spironolactone due to markedly increased hyperkalemia risk 1, 2
• Counsel patients to avoid high-potassium foods, NSAIDs, and potassium-containing salt substitutes 2, 4
• Advise patients to temporarily stop spironolactone during episodes of diarrhea or vomiting and contact their physician 4

Essential Hypertension

For hypertension, initiate spironolactone at 25-100 mg daily in single or divided doses, with dose titration at two-week intervals. 3

• Maximum practical dose is 100 mg/day, as doses >100 mg/day generally do not provide additional blood pressure reductions 1, 3
• Particularly effective in resistant hypertension when added to standard therapy 5

Edema

For edema, start at 100 mg daily (range 25-200 mg) in single or divided doses, administered for at least 5 days before increasing dose. 3

• Maximum dose is 200 mg/day 1, 3
• In cirrhotic patients, initiate therapy in a hospital setting and titrate slowly due to increased risk of complications 3

Primary Hyperaldosteronism

For primary hyperaldosteronism, administer 100-400 mg daily for preoperative preparation or long-term maintenance in patients unsuitable for surgery. 1, 3

Administration Considerations

• Can be taken with or without food, but should be taken consistently with respect to food 3
• Liquid suspension formulation (25 mg/5 mL) is available for patients with difficulty swallowing tablets 6

Common Pitfalls to Avoid

• Do not use target doses >50 mg/day in heart failure without compelling indication, as this increases hyperkalemia risk without proven benefit 1
• Do not continue potassium supplements when initiating spironolactone—this is a frequent cause of dangerous hyperkalemia 1, 2
• Do not skip early monitoring (2-3 days and 7 days post-initiation)—most serious hyperkalemia occurs in the first weeks 2
• Do not assume lower doses are ineffective—in patients unable to tolerate target doses, maintaining even 15-20 mg/day is preferable to discontinuation, as discontinuation is associated with 2-4 fold higher risk of adverse events 7