Is it better to take spironolactone (aldosterone antagonist) in the morning, at noon, or in the evening?

Spironolactone Timing: Morning Dosing is Standard

Spironolactone should be taken as a single morning dose to maximize compliance, regardless of the indication. 1, 2, 3

Standard Dosing Schedule

• Single morning dosing is the recommended approach for spironolactone across multiple clinical contexts including heart failure, hypertension, and ascites management 1, 2
• The FDA label specifies that spironolactone can be taken with or without food but should be taken consistently with respect to meals, without specifying a particular time of day 3
• Morning administration maximizes patient compliance compared to divided or multiple daily doses 1, 2

Rationale for Once-Daily Dosing

• Spironolactone has a long half-life (1.4 hours for parent compound, but 13.8-16.5 hours for active metabolites including canrenone), which supports once-daily administration 2, 3
• The active metabolites maintain therapeutic effect throughout a 24-hour period, eliminating the need for multiple daily doses 3

Evidence Across Indications

Heart Failure

• Guidelines recommend initiating at 25 mg once daily in patients with appropriate renal function and potassium levels 1, 3
• No specific time of day is mandated, though morning dosing aligns with standard practice 1

Cirrhosis and Ascites

• Single morning doses of 100 mg spironolactone (often combined with 40 mg furosemide) are standard for managing ascites 1
• This approach has been validated in the largest study ever performed, involving 3,860 patients with cirrhosis and ascites 1

Acne Treatment (Off-Label)

• Evening dosing at 100 mg daily is the typical starting approach for acne treatment in women 1, 2
• This represents the one exception where evening administration is specifically recommended, likely to minimize daytime diuretic effects 1

Comparison of Once vs. Twice-Daily Dosing

• A 1980 crossover trial found that twice-daily dosing provided only slightly better blood pressure control than once-daily dosing, with minimal clinical significance 4
• The convenience and improved compliance of once-daily dosing outweighs any marginal benefit of divided doses 4

Common Pitfall to Avoid

• Do not prescribe divided doses (e.g., twice daily) unless specifically treating acne, as this reduces compliance without meaningful clinical benefit 1, 2, 4
• Avoid evening dosing for diuretic indications, as this may cause nocturia and sleep disruption, though this is less problematic with spironolactone's mild diuretic effect compared to loop diuretics

Monitoring Regardless of Timing

• Check potassium and renal function at 3 days, 1 week, monthly for 3 months, then every 3 months 1
• Hold spironolactone if potassium exceeds 5.5 mEq/L 1, 2