What are the recommended dosing regimens of Aldactone (spironolactone) for hypertension, chronic heart failure, edema/ascites, primary hyperaldosteronism, elderly or renally impaired patients, and pediatric patients?

Aldactone (Spironolactone) Dosing Recommendations

Heart Failure with Reduced Ejection Fraction

Start spironolactone at 12.5 mg once daily in high-risk patients (creatinine >1.6 mg/dL, eGFR 30-50 mL/min/1.73m², age ≥75 years, or baseline potassium 4.5-5.0 mEq/L); otherwise start at 25 mg once daily, with a target dose of 50 mg once daily. 1

Initiation Protocol

• Baseline requirements before starting: Potassium must be ≤5.0 mEq/L, eGFR must exceed 30 mL/min/1.73m², and creatinine should ideally be <2.5 mg/dL 1
• Discontinue potassium supplements prior to initiation 1
• Standard-risk patients (eGFR >50 mL/min/1.73m², creatinine ≤1.6 mg/dL, potassium ≤4.5 mEq/L, age <75 years) may start at 25 mg daily 1

Dose Titration

• After 4-8 weeks of tolerating 25 mg daily without hyperkalemia or worsening renal function, increase to the evidence-based target dose of 50 mg once daily 2, 3, 1
• Do not exceed 50 mg daily in heart failure patients, as higher doses increase hyperkalemia risk without proven additional clinical benefit 3

Monitoring Schedule

• Check potassium and creatinine on day 3 after the first dose 1
• Recheck on day 7 1
• Additional checks at weeks 1,2,3,4, and 6 months after starting treatment 2
• Continue monitoring every 6 months thereafter 2

Hyperkalemia Management

• If potassium rises to 5.5-5.9 mEq/L: Halve the dose (e.g., 25 mg to 12.5 mg daily or switch to alternate-day dosing) and recheck within 3 days 2, 1
• If potassium reaches ≥6.0 mEq/L: Stop spironolactone immediately, monitor electrolytes closely, and initiate emergency hyperkalemia treatment 2, 1
• If creatinine rises to >220 μmol/L (2.5 mg/dL): Halve the dose and monitor closely 2
• If creatinine rises to >310 μmol/L (3.5 mg/dL): Stop spironolactone immediately 2

Essential Hypertension

For essential hypertension, use 50-100 mg daily; doses greater than 100 mg/day generally do not provide additional blood pressure reduction. 3

• The maximum practical dose is 100 mg/day 3

Primary Hyperaldosteronism

For bilateral primary aldosteronism, start spironolactone at 50-100 mg daily and titrate up to 300-400 mg daily if necessary. 4

• The dose range for primary hyperaldosteronism is 100-400 mg daily 3
• Higher starting doses (50-100 mg daily) are required compared to heart failure due to autonomous aldosterone excess 4
• Monitor potassium and creatinine within 2-3 days and again at 7 days after initiation or dose increases 4
• Continue monthly monitoring for the first 3 months, then every 3 months thereafter 4

Edema and Ascites

For cirrhotic ascites, start at 50-100 mg once daily and increase progressively up to a maximum of 400 mg/day if inadequate response. 1

• For heart failure-related edema, start at 25 mg once daily with a maximum of 50 mg daily 1
• The maximum dose for edema is 200 mg/day 3

Elderly and Renally Impaired Patients

For patients with eGFR 30-50 mL/min/1.73m², start at 12.5 mg every other day due to high hyperkalemia risk. 3, 1

• Elderly patients (≥75 years) should start at the reduced dose of 12.5 mg daily 1
• Baseline serum potassium is significantly higher in patients with renal impairment, and hyperkalemia is substantially more likely 5
• Doses greater than 25 mg/day are not recommended in patients with borderline renal function 3
• Halving the dose to 12.5 mg daily results in normalization of serum potassium in most elderly patients who develop hyperkalemia 5

Critical Safety Warnings

Drug Interactions and Contraindications

• Avoid triple therapy with ACE inhibitor + ARB + spironolactone due to markedly increased risk of severe hyperkalemia 3, 1
• Avoid concomitant NSAIDs or COX-2 inhibitors, as they impair renal function and precipitate hyperkalemia 1
• Patients on ACE inhibitors other than captopril, higher ACE inhibitor doses, and baseline elevation of creatinine or potassium are at higher risk for hyperkalemia 6

High-Risk Clinical Scenarios

• Dehydration and volume depletion markedly increase hyperkalemia risk; monitor for diarrhea or other causes of hypovolemia 1
• Worsening heart failure is a common precipitant of acute renal failure and life-threatening hyperkalemia in patients on combined ACE inhibitor and spironolactone therapy 7
• Real-world hyperkalemia rates (13-24%) are far higher than the 2% observed in controlled trials, particularly in elderly patients with diabetes and renal insufficiency 1, 7

Common Pitfalls

• Initiating 25 mg in elderly patients or those with eGFR 30-50 mL/min/1.73m² without dose reduction is a frequent and dangerous error 1
• Delaying the day-3 potassium check is critical oversight; the first week carries the highest risk for life-threatening hyperkalemia 1
• A daily spironolactone dose of 25 mg should not be exceeded in high-risk patients, as doses of 50-75 mg are associated with hyperkalemia rates of 20-24% 7, 6

Additional Adverse Effects

• Spironolactone causes breast discomfort and enlargement in approximately 10% of men; consider switching to eplerenone if this occurs 2
• Anti-androgenic effects include decreased libido and erectile dysfunction; consider switching to amiloride if problematic 1