How is Aldactone (spironolactone) used in patients with liver cirrhosis?

Aldactone (Spironolactone) in Liver Cirrhosis

First-Line Diuretic for Ascites Management

Spironolactone is the first-line diuretic for treating ascites in liver cirrhosis because it directly antagonizes the secondary hyperaldosteronism that drives sodium and water retention in these patients. 1, 2

Why Spironolactone is Superior

• Spironolactone demonstrates significantly better efficacy than loop diuretics as monotherapy, with a 95% response rate versus only 52% for furosemide alone in non-azotemic cirrhotic patients 1, 3
• Secondary hyperaldosteronism is the primary mechanism driving ascites formation in cirrhosis, making aldosterone antagonism the most physiologically rational approach 1
• Loop diuretics as monotherapy are ineffective and should never be used alone—they require aldosterone blockade to work 1, 4

Dosing Strategy

Initial Dosing

• Start with 50-100 mg/day as a single morning dose 5, 1, 2
• Titrate upward every 2-3 days based on response 5
• Maximum dose is 400 mg/day 5, 1

Monotherapy First

• Use spironolactone alone initially, increasing to 400 mg/day before adding other diuretics 5
• Only add furosemide (starting at 20-40 mg/day, maximum 160 mg/day) when spironolactone 400 mg/day proves insufficient 5

Combination Therapy When Needed

• If combination therapy is required, use a ratio of 100 mg spironolactone to 40 mg furosemide, given as a single morning dose 4
• This ratio maintains adequate serum potassium levels and can be increased simultaneously every 3-5 days if response is inadequate 4
• Combination therapy provides faster ascites resolution and reduces hyperkalemia risk compared to spironolactone monotherapy 5, 4

Monitoring Parameters

Weight Loss Goals

• Target 0.5 kg/day weight loss in patients without peripheral edema 5, 1
• In patients with peripheral edema, weight loss can be more aggressive without specific daily limits 5

Laboratory Monitoring

• Serum potassium: Check at 3 days, 1 week, then monthly for the first 3 months 4
• Serum creatinine: Monitor simultaneously with potassium 4
• Serum sodium: Watch for hyponatremia, which occurs in 8-30% of patients 1
• Urinary sodium excretion: Can assess efficacy (target >78 mmol/day) or use urinary sodium/potassium ratio (target >1) 6

Critical Contraindications

Absolute Contraindications

• Hyperkalemia >6 mmol/L 6
• Acute kidney injury 6
• Active hepatic encephalopathy 6
• Creatinine clearance <30 mL/min 4
• Baseline potassium >5.0 mEq/L 4

Relative Contraindications and Cautions

• Concomitant use of NSAIDs or COX-2 inhibitors 4
• Concomitant ACE inhibitors (requires careful monitoring and dose adjustment) 4
• Elderly patients with decreased renal function 2

When to Adjust or Stop Diuretics

Reduce or Stop Spironolactone When:

• Hyperkalemia develops (>5.5 mEq/L) 5, 4
• Creatinine rises to >2.5 mg/dL 4
• Severe hyponatremia occurs (sodium <120-125 mmol/L) 5, 4
• Hepatic encephalopathy develops without other precipitating factors 5

Reduce or Stop Furosemide When:

• Hypokalemia develops 5

Common Side Effects

Antiandrogenic Effects

• Gynecomastia (14.28% incidence) 1, 7
• Mastalgia 1
• Decreased libido, impotence, and erectile dysfunction in men 1, 6
• Menstrual irregularities in women 6

Management of Gynecomastia

• Tamoxifen 20 mg twice daily can be used to manage gynecomastia 5
• Alternative: Consider eplerenone (a selective aldosterone antagonist with no antiandrogenic effects), though it may be less effective at lower doses 7

Refractory Ascites Management

Definition

• Ascites that fails to respond to maximum diuretic doses (spironolactone 400 mg/day + furosemide 160 mg/day) for at least 1 week on salt-restricted diet (<5 g/day) 5
• Mean weight loss <800 g over 4 days with urinary sodium output less than sodium intake 5

Management Approach

• Perform large-volume paracentesis with albumin replacement (6-8 g per liter of ascites removed) 5, 1
• Reinstitute diuretics 1-2 days post-paracentesis to prevent rapid recurrence 5, 8
• Spironolactone 225 mg/day after paracentesis prevents ascites recurrence in 82% of patients versus only 7% with placebo 8

Special Considerations for Hepatic Impairment

Initiation in Hospital Setting

• Patients with hepatic disease, cirrhosis, and ascites should have spironolactone initiated in the hospital due to risk of sudden fluid and electrolyte shifts that may precipitate hepatic encephalopathy and coma 2
• Start with the lowest initial dose and titrate slowly in cirrhotic patients, as clearance of spironolactone and its metabolites is reduced 2

Practical Pitfalls to Avoid

• Never use loop diuretics as monotherapy—they are ineffective without aldosterone blockade 1, 4
• Never continue diuretics when urinary sodium excretion is <30 mmol/day in diuretic-resistant ascites 5
• Never forget to check medication list for NSAIDs or sodium-containing drugs that inhibit diuretic response 5, 4
• Never assume non-response without verifying dietary sodium compliance—measure 24-hour urinary sodium excretion 5
• Never give potassium supplements concurrently without careful monitoring, as this dramatically increases hyperkalemia risk 4