Spironolactone Dosing for Liver Disease Ascites
The recommended starting dose of spironolactone for cirrhotic ascites is 100 mg/day, which can be titrated up to a maximum of 400 mg/day based on response. 1
Initial Dosing Strategy
The approach differs based on whether this is a first episode or recurrent ascites:
First Episode of Ascites
- Start with spironolactone monotherapy at 100 mg/day 1, 2
- This generates adequate response with fewer side effects in patients presenting with their first episode 1
- Some guidelines suggest a range of 50-100 mg/day as acceptable starting doses 1, 3
Recurrent or Long-Standing Ascites
- Start with combination therapy: spironolactone 100 mg/day plus furosemide 40 mg/day 1, 3
- Maintain the 100:40 mg ratio (spironolactone:furosemide) to preserve normokalemia 3, 4
- Long-standing ascites responds better to combined diuretic treatment from the outset 1
Dose Titration Protocol
Increase doses cautiously in a stepwise fashion with at least 72-hour intervals between adjustments 1:
- Spironolactone has a long half-life; full effect of dose changes may not be seen for up to 3 days 1
- Titrate spironolactone in 100 mg increments up to maximum 400 mg/day 1
- If using combination therapy, increase furosemide up to maximum 160 mg/day while maintaining the ratio 1, 3
Target Weight Loss
Aim for weight loss of 0.5 kg/day in patients without peripheral edema, or up to 1 kg/day in patients with peripheral edema 1, 2:
- More aggressive diuresis in patients without edema risks intravascular volume depletion 1, 2
- Patients with edema have a larger fluid reservoir to mobilize safely 1
Critical Monitoring Requirements
Check serum electrolytes (sodium and potassium), creatinine, and body weight within 3-5 days of initiation and weekly during titration 3, 4, 2:
Stop or Reduce Diuretics If:
- Serum sodium drops below 120-125 mmol/L 1, 4, 2
- Serum creatinine increases >0.3 mg/dL within 48 hours 1, 4
- Serum potassium >6 mmol/L or <3 mmol/L 1, 4
- Development of overt hepatic encephalopathy 1, 4, 2
- Severe muscle cramps develop 1
Special Considerations
Grade 3 (Tense) Ascites
Perform large-volume paracentesis first with albumin (8 g per liter removed), then initiate maintenance diuretic therapy 1, 2:
- Paracentesis is faster and more effective than diuretics alone for tense ascites 1
- Follow with diuretic therapy to prevent reaccumulation 3, 2
Chronic Kidney Disease
Use higher doses of loop diuretics and lower doses of aldosterone antagonists 1:
- Spironolactone is substantially excreted by the kidney; risk of hyperkalemia is increased 5
- Monitor potassium closely in renal impairment 5
Hepatic Impairment
Initiate spironolactone in the hospital setting for patients with cirrhosis and ascites 5:
- Start with the lowest initial dose and titrate slowly 5
- Spironolactone can cause sudden alterations in fluid and electrolyte balance, precipitating hepatic encephalopathy 5
Definition of Refractory Ascites
Ascites is considered refractory only after intensive therapy with spironolactone 400 mg/day plus furosemide 160 mg/day for at least 1 week on salt restriction <5 g/day, with mean weight loss <800 g over 4 days 1, 4:
- Do not label ascites as refractory prematurely before maximizing medical therapy 4
- Consider large-volume paracentesis or TIPS only after failing maximal combination therapy 4
Common Pitfalls to Avoid
- Do not increase doses more frequently than every 72 hours due to spironolactone's long half-life 1
- Do not restrict fluids unless serum sodium <125 mmol/L 1, 4
- Do not use spironolactone monotherapy for recurrent ascites—combination therapy is more effective 1, 3
- Do not forget sodium restriction (2 g/day or 90 mmol/day)—diuretics alone are insufficient 1, 4
Alternative Agents
If spironolactone causes painful gynecomastia, switch to amiloride or eplerenone 1: