Spironolactone Dosing for Edema
Starting Dose Depends on Etiology
For cirrhotic ascites, start spironolactone at 50-100 mg once daily orally, with a maximum dose of 400 mg/day. 1 This is the drug of choice and mainstay of diuretic treatment for ascites due to cirrhosis, as aldosterone antagonists are more effective than loop diuretics alone in this population. 1
For heart failure-related edema, start at 25 mg once daily (or 25 mg every other day if eGFR 30-50 mL/min/1.73 m²), with a maximum of 50 mg daily. 1, 2 Lower doses are used in heart failure compared to cirrhosis due to higher risk of hyperkalemia in this population.
For general edema in other conditions, the FDA-approved starting dose is 25-200 mg daily, typically beginning at 100 mg daily in single or divided doses. 2
Critical Pre-Treatment Requirements
Before initiating spironolactone, you must verify:
- Serum potassium <5.0 mEq/L 1, 3, 2
- Serum creatinine <2.5 mg/dL (men) or <2.0 mg/dL (women) 1, 3
- eGFR >30 mL/min/1.73 m² 1, 3, 2
Spironolactone is contraindicated if these thresholds are exceeded. 1, 3
Dose Titration Strategy
For Cirrhotic Ascites:
- Start at 50-100 mg daily 1
- Wait 3-5 days before increasing dose, as spironolactone requires this time to reach stable concentrations and achieve natriuretic effect 1
- Increase progressively up to 400 mg/day if inadequate response 1
- Add furosemide 20-40 mg daily only if spironolactone 400 mg alone is ineffective, maintaining a 100:40 ratio of spironolactone to furosemide 1
- Never use loop diuretics as monotherapy in cirrhotic ascites 1
For Heart Failure:
- Start at 25 mg once daily (or 12.5 mg if very high risk) 1, 2
- May increase to 50 mg daily if tolerated after initial monitoring period 1, 2
- Reduce to 25 mg every other day if hyperkalemia develops on 25 mg daily 1, 2
Mandatory Monitoring Protocol
Recheck potassium and renal function within 2-3 days of initiation, then again at 7 days. 1, 3 This early monitoring is critical because real-world hyperkalemia rates (up to 24%) far exceed clinical trial rates (2%). 1
Continue monthly monitoring for first 3 months, then every 3 months thereafter. 1, 3
Management of Hyperkalemia
- If potassium >5.5 mEq/L: discontinue or reduce spironolactone dose 1
- Stop potassium supplementation before starting spironolactone 1, 3
- Counsel patients to avoid potassium-rich foods and salt substitutes 1, 3
- Instruct patients to stop spironolactone during diarrhea or when loop diuretics are interrupted 1
Critical Pitfalls to Avoid
Do not combine ACE inhibitors, ARBs, and spironolactone routinely—this triple combination dramatically increases hyperkalemia risk. 1 A population-based study showed that after widespread adoption of spironolactone in heart failure, hospitalizations for hyperkalemia increased from 2.4 to 11 per 1,000 patients, with associated mortality rising from 0.3 to 2 per 1,000. 1
In cirrhotic patients, initiate therapy in a hospital setting and titrate slowly. 2 These patients require careful monitoring due to unpredictable volume status and renal function.
Stop diuretics if serum sodium drops below 120 mmol/L, or if hepatic encephalopathy, acute kidney injury, or serum creatinine significantly increases. 1
Avoid NSAIDs and COX-2 inhibitors, which worsen renal function and precipitate hyperkalemia. 1
Special Considerations
Spironolactone causes gynecomastia, decreased libido, and erectile dysfunction due to anti-androgenic effects. 1 Consider switching to amiloride (10-40 mg/day) if gynecomastia becomes problematic, though it is less effective. 1
For patients with peripheral edema, there is no limit to daily weight loss, but for ascites without peripheral edema, limit weight loss to 0.5 kg/day to prevent intravascular volume depletion. 1
Monitor 24-hour urinary sodium excretion to assess treatment response—target >78 mmol/day on a 5 g/day salt diet. 1 If urinary sodium is >78 mmol/day but ascites persists, suspect dietary non-compliance. If <78 mmol/day, increase diuretic dose. 1