What is the recommended dosage and treatment protocol for Amphotericin B (antifungal medication) in patients with severe fungal infections?

Amphotericin B Dosing and Treatment Protocol for Severe Fungal Infections

For severe invasive fungal infections, use lipid formulations of amphotericin B at 3-5 mg/kg/day IV as first-line therapy due to equivalent efficacy with significantly reduced nephrotoxicity compared to conventional amphotericin B deoxycholate, which should be dosed at 0.5-1.0 mg/kg/day IV (maximum 1.5 mg/kg/day) only when lipid formulations are unavailable. 1, 2

Lipid Formulation Dosing (Preferred)

Lipid formulations provide equivalent antifungal efficacy with markedly superior renal safety profiles and should be prioritized over conventional amphotericin B. 1, 3

Standard Dosing by Formulation:

• Liposomal amphotericin B (AmBisome): 3-5 mg/kg/day IV for most infections 4, 1, 5
• Amphotericin B lipid complex (ABLC/Abelcet): 5 mg/kg/day IV 1, 3
• Amphotericin B colloidal dispersion (ABCD): 3-6 mg/kg/day IV (note: no longer commercially available in many regions) 4, 3

CNS Involvement:

• Liposomal amphotericin B: 5-10 mg/kg/day IV for CNS infections including cryptococcal meningitis and CNS candidiasis 4, 5
• Duration: 4-6 weeks for induction and consolidation phases 5

Conventional Amphotericin B Deoxycholate Dosing

Use only when lipid formulations are unavailable or cost-prohibitive. 1

Dosing Protocol:

• Test dose: 1 mg in 20 mL of 5% dextrose over 20-30 minutes, monitoring vital signs every 30 minutes for 2-4 hours 2
• Initial dose: 0.25 mg/kg/day IV for patients with good cardio-renal function and well-tolerated test dose 2
• Severe/rapidly progressive infections: 0.3 mg/kg/day IV initially, escalating to 0.5-1.0 mg/kg/day 1, 2
• Impaired renal function or severe test dose reaction: Start with 5-10 mg/day, increase by 5-10 mg increments daily 2
• Maximum dose: Never exceed 1.5 mg/kg/day due to risk of fatal cardiac arrest 1, 2

Infection-Specific Dosing

Candidemia and Invasive Candidiasis:

• Conventional amphotericin B: 0.6-1.0 mg/kg/day IV 4, 1
• Lipid formulations: 3-5 mg/kg/day IV 4, 1
• Duration: 14 days after last positive blood culture and resolution of signs/symptoms 1
• CNS candidiasis: Liposomal amphotericin B 5 mg/kg/day IV with or without flucytosine 25 mg/kg four times daily 4, 1

Aspergillosis:

• Lipid formulations: 3-5 mg/kg/day IV 4
• Total cumulative dose: Up to 3.6 g for documented aspergillosis 2

Sporotrichosis:

• Severe disease: Lipid formulation 3-5 mg/kg/day IV OR conventional amphotericin B 0.7-1.0 mg/kg/day IV 4
• Duration: Until favorable response, then switch to itraconazole 200 mg twice daily to complete ≥12 months total therapy 4

Mucormycosis (Rhinocerebral Phycomycosis):

• Recommended cumulative dose: At least 3 g (minimum where deep tissue invasion evident) 2
• Approach: Aggressive dosing required due to rapidly fatal course; combine with surgical debridement 5, 2

Pediatric Dosing

• Invasive candidiasis: 0.5-1.5 mg/kg/day IV or 50 mg/m²/day 1
• Neonatal disseminated candidiasis: 1 mg/kg/day IV 1
• Premature/low birth weight infants with cutaneous candidiasis: 0.5-1 mg/kg/day for total dose of 10-25 mg/kg 1

Critical Administration Protocol

Pre-Infusion Requirements:

• Hydration: Administer 1 liter of 0.9% normal saline 30 minutes before infusion in patients who can tolerate fluids 1, 6
• Pre-medication: Diphenhydramine or acetaminophen to reduce infusion-related reactions 6, 5

Infusion Parameters:

• Conventional amphotericin B: Infuse over 2-6 hours at concentration of 0.1 mg/mL (1 mg/10 mL) in 5% dextrose with pH >4.2 2
• Lipid formulations: Follow manufacturer-specific infusion rates 3

Post-Infusion:

• Additional hydration: 1 liter of 0.9% normal saline after infusion 6

Monitoring Requirements

Monitor throughout therapy to detect toxicity early: 1, 6

• Renal function: Serum creatinine and BUN regularly
• Electrolytes: Potassium and magnesium (hypokalemia occurs in 6.2% of patients) 7
• Liver function tests: Monitor for hepatotoxicity (occurs in 5.2% of patients) 7
• Infusion reactions: Fever, chills, rigors, nausea, vomiting, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, urticaria 1, 6

Critical Pitfalls to Avoid

1. Never exceed 1.5 mg/kg/day of conventional amphotericin B—fatal cardiac arrest can occur 1, 2

2. Do not skip pre-hydration with normal saline—this dramatically increases nephrotoxicity risk 1, 6

3. Do not interchange lipid formulations without dose adjustment—they have different pharmacokinetics and toxicity profiles 1, 3

4. Do not use conventional amphotericin B when lipid formulations are available for patients with baseline renal impairment 1, 3

5. Do not use ABCD (colloidal dispersion) as first-line—it has equivalent or worse infusion-related reactions compared to conventional amphotericin B despite reduced nephrotoxicity 3, 8

6. Do not reconstitute conventional amphotericin B in solutions with pH <4.2—use only 5% dextrose with appropriate pH 2

Comparative Safety Data

Nephrotoxicity rates differ substantially between formulations: 7, 3

• Conventional amphotericin B: Significant dose-limiting nephrotoxicity
• Liposomal amphotericin B: 4.2% nephrotoxicity rate at approved dosages 7
• ABLC: Reduced nephrotoxicity but higher than liposomal formulation 3
• ABCD: Reduced nephrotoxicity but dose-limited by severe infusion reactions 3, 8

In the only head-to-head comparison, liposomal amphotericin B demonstrated significantly lower infusion-related events and nephrotoxicity compared to ABLC. 3