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) 3
Specific Lipid Formulation Dosing
- Liposomal amphotericin B: 3-5 mg/kg IV once daily for invasive disease 4, 5
- Liposomal amphotericin B (cryptococcal meningitis): 4-6 mg/kg IV once daily 1
- Amphotericin B lipid complex: 5 mg/kg IV once daily 4
Age-Related Considerations
Clearance decreases substantially with age, requiring dose adjustments: 6
- Children 8 months to 9 years: mean clearance 0.57 ± 0.15 ml/min/kg 6
- Children >9 years: mean clearance 0.24 ± 0.02 ml/min/kg 6
- Older children may require lower doses per kilogram to decrease toxicity potential 6
- Elimination half-life inversely correlates with patient age (younger children clear drug faster) 7
Administration Guidelines
Infusion Protocol
- Administer in 5% dextrose in water to achieve final concentration of 0.1 mg/mL 3
- Standard infusion time: 1-2 hours for doses ≤1 mg/kg 3, 8
- Extended infusion time: 3-6 hours for patients with azotemia, hyperkalemia, or receiving high doses (>1 mg/kg) 3
- Rapid dose escalation over 1 hour is well-tolerated in pediatric bone marrow transplant recipients 8
Premedication for Infusion Reactions
- Hydration with 0.9% saline IV over 30 minutes before amphotericin B infusion reduces nephrotoxicity 3
Monitoring Requirements
Renal Function
- Significant increases in serum creatinine occur, especially at doses ≥5 mg/kg/day of liposomal formulation 9
- Monitor serum creatinine and urea throughout therapy 7
- Nephrotoxicity is exacerbated by concomitant nephrotoxic drugs 3
Electrolytes
- Monitor serum potassium closely; hypokalemia from tubular damage is common 3, 7
- Greater hypokalemia occurs at higher dosage levels (10 mg/kg/day) 9
Hematologic Parameters
- Monitor hemoglobin and platelets; significant decreases occur during therapy 7
Hepatic Function
- Monitor aspartate transaminase; significant increases occur during therapy 7
- Hepatotoxicity occurs more frequently with liposomal amphotericin B (83%) than conventional formulation (56%) 10
Therapeutic Drug Monitoring
- Target serum trough levels: avoid exceeding 2 mg/L 8
- Therapeutic target: maintain concentrations >0.3 μg/mL, ideally >0.5 μg/mL 7
- Consider individualized dosing based on therapeutic drug monitoring due to large pharmacokinetic variability (>3-fold in clearance, >8-fold in volume of distribution) 7
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 9
- Infusion reactions are similar between conventional (23%) and liposomal (9%) formulations when appropriately administered 10
- Infusion reactions are rare in children <90 days of age 10
- Acute infusion-related reactions more common at 7.5-10 mg/kg dosage levels 9