Maximum Recommended Dose of Spironolactone
The maximum recommended dose of spironolactone is 400 mg daily for patients with cirrhosis and ascites, and 50 mg daily for heart failure patients. 1, 2
Indication-Specific Maximum Dosing
Cirrhosis with Ascites
- Initial dose typically starts at 100 mg daily, which can be progressively increased in a stepwise fashion 1
- Dose increases should occur every 3-5 days (maintaining a 100 mg spironolactone:40 mg furosemide ratio when used in combination) 1
- Maximum dose is 400 mg daily for management of ascites in cirrhosis 1
- When combined with furosemide, the maximum recommended doses are 400 mg/day of spironolactone and 160 mg/day of furosemide 1, 3
Heart Failure
- Initial dose is 25 mg daily for heart failure patients with normal renal function 1, 2
- Maximum recommended dose is 50 mg daily for heart failure patients 1, 2
- For patients with eGFR between 30-50 mL/min/1.73m², consider lower dosing (12.5-25 mg daily or every other day) 2, 4
- Spironolactone is contraindicated in patients with eGFR <30 mL/min/1.73m² due to risk of hyperkalemia 2
Primary Hyperaldosteronism
- Doses of 100 mg to 400 mg daily are recommended in preparation for surgery 4
- For long-term maintenance therapy in patients unsuitable for surgery, the lowest effective dose should be used 4
Essential Hypertension
- Initial daily dose is 25 mg to 100 mg 4
- Doses greater than 100 mg/day generally do not provide additional blood pressure reduction 4, 5
Monitoring and Safety Considerations
Dose Titration
- When increasing doses, allow at least 72 hours between dose adjustments due to spironolactone's long half-life 1
- For cirrhosis, monitor spot urine sodium/potassium ratio to guide dosing (ratio >1 indicates effective natriuresis) 1
- For heart failure, recheck renal function and electrolytes 1 and 4 weeks after starting treatment or increasing dose 1
Adverse Effects Monitoring
- Monitor serum potassium and renal function closely, especially during the first month of treatment 1, 2
- If potassium rises to >5.5 mmol/L, reduce dose by half; if >6.0 mmol/L, discontinue immediately 1, 2
- If creatinine rises to >220 μmol/L (2.5 mg/dL), reduce dose; if >310 μmol/L (3.5 mg/dL), discontinue 1
- Gynecomastia occurs in approximately 10% of men, especially at higher doses 1, 2, 6
- Consider switching to eplerenone in men experiencing gynecomastia 1, 2
Special Considerations
- In patients with renal impairment, lower maximum doses are recommended 1, 2
- Discontinue spironolactone if severe hyponatremia (serum sodium <120 mmol/L), progressive renal failure, worsening hepatic encephalopathy, or incapacitating muscle cramps occur 1
- For patients with cirrhosis, initiate therapy in a hospital setting and titrate slowly 4
- There appears to be no additional benefit for doses above 50 mg/day for hypertension 5
- High-dose spironolactone (75-300 mg) has been studied in acute heart failure with favorable decongestion outcomes and acceptable safety profile 7