What is the recommended dose of spironolactone (lasilactone) in pediatric patients with hypertension or heart failure, considering factors such as age, weight, and renal function?

Spironolactone Dosing in Pediatric Patients

For children with hypertension, heart failure, or edema, initiate spironolactone at 1 mg/kg/day (given once daily or divided twice daily), with a maximum dose of 3.3 mg/kg/day up to 100 mg/day. 1, 2

Initial Dosing Strategy

• Start at 1 mg/kg/day for most pediatric indications including hypertension, heart failure, and ascites 1, 2
• Administer either once daily (QD) or divided twice daily (BID) 1, 2
• For infants and young children with heart failure or ascites, the typical starting range is 1-2 mg/kg/day 2, 3
• The absolute maximum is 3.3 mg/kg/day up to 100 mg/day 1, 2

Dose Titration Protocol

• Increase doses at 3-5 day intervals because spironolactone and its active metabolites require 3-4 days to achieve stable concentrations 2, 4
• Do not escalate more frequently, as the clinical response is slow to appear due to the drug's long half-life 2
• For resistant cases, doses up to 4 mg/kg/day have been used, though this exceeds standard guideline recommendations 2
• Older pediatric literature suggests higher initial dosing (2-3 mg/kg/day for infants, 4-5 mg/kg/day for older children) for the first 2-5 days, then reducing to maintenance doses 3, but current guidelines favor the more conservative 1 mg/kg/day starting dose 1, 2

Critical Monitoring Requirements

Before initiating therapy:

• Check serum potassium, sodium, and renal function 1, 2
• Verify adequate urine output, particularly in patients with ascites or heart failure 2

After starting or changing dose:

• Check potassium and renal function within 5-7 days 1, 2
• Continue monitoring every 5-7 days until potassium values stabilize 1, 2
• Once stable, monitor at 1-2 weeks, then at 3 months, and subsequently at 6-month intervals 2

Safety Thresholds and Actions

• Hold or reduce dose if potassium >5.5 mEq/L 1, 2
• Discontinue immediately if potassium >6.0 mEq/L 1, 2, 3
• Stop therapy if serum sodium falls below 125 mmol/L 2

Combination Therapy Considerations

When combining with furosemide (as in "lasilactone" formulations):

• The recommended ratio is spironolactone 100 mg : furosemide 40 mg to maintain normokalemia 2
• For pediatric dosing, furosemide is typically started at 0.5 mg/kg per dose twice daily and increased as needed 2
• Add furosemide either from the outset or when dose increases in spironolactone are required and/or if hyperkalemia occurs 2
• This combination approach mirrors adult cirrhosis guidelines where aldosterone antagonists are the mainstay, with loop diuretics added for inadequate response 2

Important caveat: The fixed-dose combination product "lasilactone" (furosemide 20 mg + spironolactone 50 mg) studied in adults 5 is not appropriate for weight-based pediatric dosing and should not be used in children.

Critical Drug Interactions and Contraindications

• Discontinue potassium supplements when starting spironolactone to avoid severe hyperkalemia 2
• Potassium-sparing diuretics may cause severe hyperkalemia, especially if given with an ACE inhibitor or ARB 1
• Use only if hypokalaemia persists after initiation of therapy with ACE inhibitors and diuretics 1
• The combination of spironolactone with ACE inhibitors or ARBs requires extremely close monitoring and dramatically increases hyperkalemia risk 2

Special Clinical Scenarios

For ascites management:

• Sodium restriction to less than 2 mmol/kg per day is essential alongside spironolactone therapy 2
• Infants fed only breast milk or formula receive about 1 mmol/kg per day and typically fall within safe limits 2
• Water restriction is generally recommended when serum sodium is reduced to ≤125 mEq/L 2

Pharmacokinetic considerations:

• Body weight explains 22% of inter-individual variability in spironolactone clearance 4
• The pharmacokinetics of spironolactone and its metabolites is highly variable between patients below 2 years of age 4
• This variability highlights the need for weight-based dosing and careful monitoring in this population 4, 6

Common Pitfalls to Avoid

• Failing to monitor potassium levels regularly after initiating spironolactone can lead to life-threatening hyperkalemia, particularly in patients with renal impairment or those on RAAS inhibitors 1, 2
• Not checking renal function before initiating therapy can result in dangerous hyperkalemia in patients with unrecognized kidney disease 1, 2
• Administering potassium supplements concurrently without careful monitoring can cause severe hyperkalemia 2
• Dose escalation too rapidly (faster than every 3-5 days) fails to account for the drug's long half-life and delayed clinical response 2