What is the maximum recommended dose of spironolactone (aldosterone antagonist) per day?

Maximum Dose of Spironolactone

The maximum recommended dose of spironolactone is 400 mg per day for cirrhotic ascites and primary hyperaldosteronism, while 50 mg per day is the maximum for heart failure. 1, 2

Context-Specific Maximum Dosing

Cirrhotic Ascites

• Maximum dose: 400 mg/day 1
• Start at 50-100 mg/day and increase gradually every 3-5 days based on response 1
• The long half-life requires waiting at least 72 hours between dose adjustments to see full effect 1
• This maximum dose defines the threshold for determining medical treatment refractoriness in ascites management 1

Heart Failure

• Maximum dose: 50 mg/day 2
• Start at 25 mg once daily in patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m² 2
• Titrate to 50 mg once daily only if the patient tolerates 25 mg without hyperkalemia 2
• For eGFR 30-50 mL/min/1.73 m², consider initiating at 25 mg every other day due to hyperkalemia risk 2
• Higher doses (75-300 mg/day) have been studied in acute heart failure but are not FDA-approved and carry increased hyperkalemia risk 3

Hypertension

• Maximum effective dose: 100 mg/day 2, 4
• Start at 25-100 mg/day in single or divided doses 2
• Doses >100 mg/day generally provide no additional blood pressure reduction 2
• Titrate at two-week intervals 2

Primary Hyperaldosteronism

• Maximum dose: 400 mg/day 2
• Typical range is 100-400 mg daily for surgical preparation or long-term maintenance 2

Critical Safety Considerations

Hyperkalemia Risk Increases Dramatically with Dose

• At 12.5 mg/day: 5% incidence of hyperkalemia (≥5.5 mmol/L) 5
• At 25 mg/day: 13% incidence 5
• At 50 mg/day: 20% incidence 5
• At 75 mg/day: 24% incidence 5
• This dose-dependent hyperkalemia risk is the primary reason maximum doses differ by indication 5

Predictors of Hyperkalemia Requiring Lower Maximum Doses

• Baseline serum creatinine >1.6 mg/dL or potassium >5.0 mEq/L 5
• eGFR <50 mL/min/1.73 m² 2
• Concomitant ACE inhibitors or ARBs (especially non-captopril ACE inhibitors) 5
• Diabetes mellitus 6
• Elderly patients 6

Monitoring Requirements at Higher Doses

• Check potassium and creatinine at 3 days, 1 week, then monthly for first 3 months 6
• If potassium >5.5 mEq/L, reduce dose or switch to every-other-day dosing 6, 2
• If creatinine rises to >2.5 mg/dL (220 μmol/L), halve the dose 6
• If creatinine >3.5 mg/dL (310 μmol/L), stop spironolactone immediately 6

Common Pitfalls to Avoid

Don't Exceed Context-Appropriate Maximums

• Using 400 mg/day in heart failure patients is dangerous and not evidence-based 2, 5
• The RALES trial that established spironolactone's mortality benefit in heart failure used only 25 mg/day 7

Don't Ignore the Dose-Response Plateau

• In hypertension, doses >100 mg/day provide no additional benefit 2, 4
• In cirrhotic ascites, while 400 mg/day is the maximum, many patients respond to lower doses 1

Don't Rush Dose Escalation

• Wait 3-5 days between increases due to the long half-life 1
• Premature escalation leads to cumulative hyperkalemia 1

Don't Continue High Doses Once Goals Are Met

• Once ascites is controlled, taper to the lowest effective dose 1
• Continuing maximum doses unnecessarily increases adverse event risk 1