What is the recommended dose and indication for liposomal (Liposomal Amphotericin B) treatment?

Liposomal Amphotericin B: Dosing and Indications

Liposomal amphotericin B is indicated for invasive fungal infections at 3-5 mg/kg/day IV for most systemic infections, with higher doses of 5-10 mg/kg/day reserved for CNS involvement, and is preferred over conventional amphotericin B due to significantly reduced nephrotoxicity while maintaining equivalent efficacy. 1, 2, 3

Primary Indications

Invasive Candidiasis and Candidemia

• Use liposomal amphotericin B at 3-5 mg/kg/day IV for fluconazole/voriconazole-resistant Candida isolates, with or without flucytosine 25 mg/kg four times daily. 1
• Consider liposomal amphotericin B when there is persistent candidemia or clinical unresponsiveness to echinocandins without evidence of amphotericin B resistance. 3
• Continue treatment for 14 days after the last positive blood culture and resolution of signs and symptoms. 2, 4

CNS Candidiasis (Meningitis)

• Administer liposomal amphotericin B at 5 mg/kg/day IV, with or without flucytosine 25 mg/kg four times daily, until all signs, symptoms, CSF abnormalities, and radiological findings resolve. 1, 2
• Remove infected CNS devices (ventriculostomy drains, shunts, stimulators) whenever possible. 1

Candida Endophthalmitis

• For fluconazole/voriconazole-resistant isolates causing chorioretinitis, use liposomal amphotericin B at 3-5 mg/kg/day IV with or without flucytosine 25 mg/kg four times daily. 1
• With macular involvement or vitritis, add intravitreal injection of amphotericin B deoxycholate 5-10 μg/0.1 mL sterile water to ensure prompt high-level antifungal activity. 1
• Treat for at least 4-6 weeks with duration dependent on resolution of lesions by repeated ophthalmological examinations. 1

Invasive Mold Infections (Aspergillosis, Mucormycosis)

• For severe fungal infections without CNS involvement, use liposomal amphotericin B at 5 mg/kg/day IV; for CNS involvement, increase to 10 mg/kg/day IV. 3
• Treat for 4-6 weeks during induction and consolidation phases. 3
• For COVID-19 associated mucormycosis, combine antifungal therapy with immediate surgical debridement. 3
• Maintenance therapy should continue for 3-6 months until resolution of clinical signs and symptoms. 3

Empirical Therapy in Febrile Neutropenia

• Liposomal amphotericin B at 3 mg/kg/day IV is effective as empirical therapy in neutropenic patients with persistent fever despite antibacterial treatment. 4, 5
• Treatment is typically given for 1-2 weeks. 5

Special Populations

Neonates:

• For disseminated candidiasis in neonates, conventional amphotericin B at 1 mg/kg/day IV is recommended rather than liposomal formulation. 2, 4
• For neonatal disseminated cutaneous candidiasis in premature/low birth weight infants, use 0.5-1 mg/kg/day for a total dose of 10-25 mg/kg. 2

Pediatric Patients:

• Dose at 0.5-1.5 mg/kg/day IV or 50 mg/m²/day for invasive candidiasis. 2

Pregnancy:

• Liposomal amphotericin B at 3-5 mg/kg/day is the preferred antifungal for severe fungal infections during pregnancy. 4

Dosing Algorithm by Clinical Scenario

Standard Systemic Infections (No CNS Involvement)

• Start at 3-5 mg/kg/day IV 1, 2, 3
• This applies to candidemia, invasive candidiasis, and most aspergillosis cases

CNS Infections

• Start at 5 mg/kg/day IV for Candida meningitis 1, 2
• Escalate to 10 mg/kg/day IV for invasive mold infections with CNS involvement 3

Refractory or Severe Disease

• Higher doses up to 10 mg/kg/day may be considered, though a randomized trial showed no statistical difference in efficacy between 3 mg/kg/day and 10 mg/kg/day for invasive mold infections, with the standard dose being better tolerated. 5

Administration Guidelines

Pre-medication and Hydration

• Administer 1 liter of 0.9% normal saline 30 minutes before infusion in patients who can tolerate fluids to reduce nephrotoxicity. 2, 4
• Pre-medicate with diphenhydramine or acetaminophen prior to infusion to avoid infusion-related reactions. 3, 4

Infusion Parameters

• Infuse over 2-6 hours depending on dose. 6
• The recommended concentration for intravenous infusion is 0.1 mg/mL (1 mg/10 mL). 6

Critical Safety Considerations

Maximum Dose Restrictions

• Never exceed 1.5 mg/kg/day total dose of conventional amphotericin B due to risk of fatal cardiac arrest; this restriction does not apply to liposomal formulations which are routinely dosed at 3-10 mg/kg/day. 2, 6

Monitoring Requirements

• Monitor renal function, electrolytes (particularly potassium and magnesium), and liver function tests regularly throughout therapy. 2, 4
• Watch for infusion-related reactions: fever, chills, nausea, vomiting, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, urticaria. 2

Toxicity Profile

• Liposomal amphotericin B has significantly fewer infusion-related adverse events and less nephrotoxicity compared to conventional amphotericin B deoxycholate and amphotericin B lipid complex. 5, 7, 8
• In comparative studies, liposomal amphotericin B demonstrated superior tolerability to other lipid formulations, with one double-blind trial showing significantly lower infusion-related events and nephrotoxicity compared to amphotericin B lipid complex. 7, 8

Common Pitfalls to Avoid

• Do not interchange different lipid formulations (liposomal amphotericin B, amphotericin B lipid complex, amphotericin B colloidal dispersion) without careful consideration, as they have different pharmacological properties, dosing requirements, and toxicity profiles. 1, 2
• Do not skip pre-hydration with normal saline, as this significantly increases nephrotoxicity risk. 2
• Do not use conventional amphotericin B when lipid formulations are available for patients with renal impairment. 2
• Do not assume higher doses are always better—the AmBiLoad trial showed no efficacy benefit of 10 mg/kg/day over 3 mg/kg/day for invasive mold infections, with worse tolerability at the higher dose. 5

Alternative Formulations When Liposomal Amphotericin B Unavailable

• If liposomal amphotericin B is unavailable, alternatives include amphotericin B deoxycholate at 1-1.5 mg/kg/day administered in 5% dextrose with slow infusion over 6-8 hours. 3
• For maintenance therapy after initial response, consider posaconazole or isavuconazole. 3

Evidence Quality Considerations

The 2016 IDSA Candidiasis Guidelines provide the most authoritative and recent guidance, though most recommendations carry low-quality evidence ratings, reflecting the challenges of conducting large randomized trials in critically ill patients with invasive fungal infections. 1 The consistent finding across multiple studies is that liposomal amphotericin B maintains equivalent efficacy to conventional amphotericin B while substantially reducing toxicity, making it the preferred formulation when cost is not prohibitive. 5, 7, 8