What is the recommended dose of amphotericin B for pediatric patients?

Amphotericin B Pediatric Dosing

For invasive fungal infections in children, amphotericin B deoxycholate should be dosed at 0.5-1.5 mg/kg IV once daily, with the specific dose within this range determined by disease severity and patient tolerance. 1

Standard Dosing by Clinical Scenario

Invasive Candidiasis

• Conventional amphotericin B deoxycholate: 0.5-1.5 mg/kg IV once daily 1
• For mild-to-moderate disease: initiate at 0.25-0.5 mg/kg IV once daily, then increase as tolerated to 0.5-1.5 mg/kg IV once daily 1
• For severe disease: initiate treatment at target daily dose (0.5-1.5 mg/kg) immediately 1
• Lipid formulations: 5 mg/kg IV once daily for patients with renal insufficiency or infusion-related toxicity 1

Cryptococcal Meningitis (CNS Disease)

• Amphotericin B deoxycholate: 0.7-1.0 mg/kg IV daily PLUS flucytosine 100 mg/kg/day orally divided into 4 doses 1
• Liposomal amphotericin B: 6 mg/kg IV daily (alternative for induction therapy) 1
• If flucytosine not tolerated: amphotericin B 0.7-1.5 mg/kg IV once daily as monotherapy 1

Coccidioidomycosis

• Diffuse pulmonary or disseminated disease: 0.5-1.0 mg/kg IV once daily until clinical improvement (minimum several weeks) 1

Neonatal Invasive Candidiasis

• Amphotericin B deoxycholate: 1-1.5 mg/kg/day IV as single daily dose 2
• Liposomal amphotericin B: 2.5-7 mg/kg/day IV as single daily dose (alternative formulation) 2
• For hematogenous Candida meningoencephalitis (HCME): consider higher doses and longer treatment courses 2

Lipid Formulations

When to Use Lipid Formulations

• Renal insufficiency or pre-existing renal dysfunction 1
• Infusion-related toxicity to conventional amphotericin B 1
• Patients requiring higher doses (>1 mg/kg) 1

Specific Lipid Formulation Dosing

• Liposomal amphotericin B: 3-5 mg/kg IV once daily for invasive disease 1
• Liposomal amphotericin B (cryptococcal meningitis): 4-6 mg/kg IV once daily 1
• Amphotericin B lipid complex: 5 mg/kg IV once daily 1

Age-Related Considerations

Clearance decreases substantially with age, requiring dose adjustments: 3

• Children 8 months to 9 years: mean clearance 0.57 ± 0.15 ml/min/kg 3
• Children >9 years: mean clearance 0.24 ± 0.02 ml/min/kg 3
• Older children may require lower doses per kilogram to decrease toxicity potential 3
• Elimination half-life inversely correlates with patient age (younger children clear drug faster) 4

Administration Guidelines

Infusion Protocol

• Administer in 5% dextrose in water to achieve final concentration of 0.1 mg/mL 1
• Standard infusion time: 1-2 hours for doses ≤1 mg/kg 1, 5
• Extended infusion time: 3-6 hours for patients with azotemia, hyperkalemia, or receiving high doses (>1 mg/kg) 1
• Rapid dose escalation over 1 hour is well-tolerated in pediatric bone marrow transplant recipients 5

Premedication for Infusion Reactions

• Hydration with 0.9% saline IV over 30 minutes before amphotericin B infusion reduces nephrotoxicity 1

Monitoring Requirements

Renal Function

• Significant increases in serum creatinine occur, especially at doses ≥5 mg/kg/day of liposomal formulation 6
• Monitor serum creatinine and urea throughout therapy 4
• Nephrotoxicity is exacerbated by concomitant nephrotoxic drugs 1

Electrolytes

• Monitor serum potassium closely; hypokalemia from tubular damage is common 1, 4
• Greater hypokalemia occurs at higher dosage levels (10 mg/kg/day) 6

Hematologic Parameters

• Monitor hemoglobin and platelets; significant decreases occur during therapy 4

Hepatic Function

• Monitor aspartate transaminase; significant increases occur during therapy 4
• Hepatotoxicity occurs more frequently with liposomal amphotericin B (83%) than conventional formulation (56%) 7

Therapeutic Drug Monitoring

• Target serum trough levels: avoid exceeding 2 mg/L 5
• Therapeutic target: maintain concentrations >0.3 μg/mL, ideally >0.5 μg/mL 4
• Consider individualized dosing based on therapeutic drug monitoring due to large pharmacokinetic variability (>3-fold in clearance, >8-fold in volume of distribution) 4

Common Pitfalls and Caveats

Critical Errors to Avoid

• Failure to consider CNS involvement (HCME) when treating neonatal candidiasis requires higher doses and longer treatment 2
• Not adjusting dosing based on specific amphotericin B formulation (conventional vs. lipid formulations have different dose ranges) 2
• Starting at full target dose in mild-to-moderate disease increases infusion reactions; gradual escalation is safer 1
• Using fluconazole for empiric treatment of fungemia without culture data (non-albicans Candida species may be resistant) 1

Infusion-Related Reactions

• Infusion reactions occur in approximately 11% of infusions in pediatric patients 6
• Infusion reactions are similar between conventional (23%) and liposomal (9%) formulations when appropriately administered 7
• Infusion reactions are rare in children <90 days of age 7
• Acute infusion-related reactions more common at 7.5-10 mg/kg dosage levels 6

Duration of Therapy

• Candidemia: treat until 2-3 weeks after last positive blood culture 1
• Treatment duration based on presence of deep tissue foci and clinical response 1
• Remove central venous catheters when feasible in HIV-infected children with fungemia 1