What is the recommended dose of Spironolactone (Lasilactone) for pediatric patients with Chronic Liver Disease?

Spironolactone Dosing for Pediatric Chronic Liver Disease with Ascites

For pediatric patients with chronic liver disease and ascites, start spironolactone at 1 mg/kg/day as a single morning dose, which can be increased up to a maximum of 3.3 mg/kg/day (not exceeding 100 mg/day), typically combined with furosemide 0.5-2 mg/kg/day if needed for adequate diuresis. 1

Initial Dosing Strategy

• Begin with spironolactone monotherapy at 1 mg/kg/day given once daily in the morning 1
• The pediatric cardiovascular guidelines establish this as the standard starting dose for children requiring aldosterone antagonist therapy 1
• For children with moderate ascites (Grade 2), aldosterone antagonists alone are often sufficient as first-line therapy, similar to adult cirrhosis management 1

Dose Escalation Protocol

• Increase spironolactone gradually every 3-5 days if weight loss and natriuresis are inadequate 1
• The maximum dose is 3.3 mg/kg/day, not to exceed 100 mg/day total 1
• Spironolactone has a long half-life requiring 3-4 days to reach steady state, so dose adjustments should be made cautiously with at least 72-hour intervals 1

Combination Therapy with Furosemide

• If spironolactone monotherapy fails to control ascites, add furosemide at 0.5-2 mg/kg per dose, given once or twice daily 1
• The maximum furosemide dose is 6 mg/kg/day 1
• Maintain a ratio approximating 100:40 (spironolactone:furosemide) when using combination therapy, similar to adult dosing principles 1
• For recurrent or long-standing ascites, initial combination therapy may be more effective than sequential addition 1, 2

Critical Monitoring Requirements

Monitor the following parameters closely:

• Daily weights targeting 0.3-0.5 kg loss per day in children without peripheral edema 1
• Serum electrolytes (sodium, potassium) every 3-7 days during initial titration 1
• Renal function (creatinine) at baseline and with each dose adjustment 1
• Spironolactone commonly causes hyperkalemia, particularly at higher doses 1, 3

Absolute Contraindications to Dose Escalation

Stop or reduce diuretics immediately if:

• Severe hyponatremia develops (serum sodium <120-125 mmol/L) 1
• Hyperkalemia occurs (potassium >5.5 mmol/L) 1, 3
• Acute kidney injury or progressive renal failure develops 1
• Hepatic encephalopathy worsens 1
• Marked hypotension or hypovolemia occurs 1

Important Clinical Caveats

• Spironolactone exhibits highly variable pharmacokinetics in infants and young children, with body weight explaining only 22% of clearance variability 4
• This variability necessitates individualized dose titration based on clinical response rather than rigid weight-based calculations 4
• Painful gynecomastia may develop with spironolactone; consider switching to amiloride (10-40 mg/day, approximately 1/10 the spironolactone dose) if this occurs 1
• For tense ascites (Grade 3), large-volume paracentesis with albumin should be performed first, followed by maintenance diuretic therapy 1
• Aggressive nutritional support is essential in pediatric liver disease, as these children require 20-80% more calories than healthy children 1

When Diuretics Fail

• Ascites refractory to maximum doses (spironolactone 3.3 mg/kg/day + furosemide 6 mg/kg/day) requires alternative management 1
• Consider serial large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation evaluation 1, 5
• Refractory ascites carries a poor prognosis, with only 50% 2-5 year survival in adult cirrhosis 5