What is the recommended intravenous administration protocol for liposomal amphotericin B (AmBisome)?

How to Administer Liposomal Amphotericin B

Administer liposomal amphotericin B intravenously at 3-5 mg/kg/day for most invasive fungal infections, with higher doses of 5-10 mg/kg/day reserved for CNS involvement, infused over 2 hours through a dedicated IV line after premedication with diphenhydramine or acetaminophen. 1, 2

Pre-Infusion Preparation

Premedication is essential to reduce infusion-related reactions:

• Administer diphenhydramine or acetaminophen approximately 30 minutes before infusion 1, 3
• Infuse 1 liter of normal saline 30 minutes before amphotericin B in patients who can tolerate fluids to reduce nephrotoxicity 1, 3
• Reserve glucocorticosteroids (such as hydrocortisone) only for rare cases where severe infusion-related reactions occur despite standard premedication 1
• If glucocorticosteroids are needed, administer approximately 30 minutes before the infusion 1

Standard Dosing by Clinical Indication

The dose varies significantly based on infection site and severity:

For Most Invasive Fungal Infections (Without CNS Involvement)

• Standard dose: 3-5 mg/kg IV daily 4, 1, 2
• This applies to candidemia, invasive candidiasis, aspergillosis, and most systemic fungal infections 4

For CNS Infections (Meningitis, Brain Abscesses)

• CNS dose: 5-10 mg/kg IV daily 4, 1, 2
• For cryptococcal meningitis specifically: 5 mg/kg daily with or without flucytosine 25 mg/kg four times daily 4
• Consider adding flucytosine 25 mg/kg four times daily for enhanced efficacy in CNS infections 4

For Fluconazole-Resistant Candida Endophthalmitis

• Dose: 3-5 mg/kg IV daily with or without oral flucytosine 4
• May require intravitreal injection in addition to systemic therapy for macular involvement 4

For Neonates

• Use conventional amphotericin B deoxycholate 1 mg/kg/day instead as first-line for disseminated candidiasis 4
• Liposomal amphotericin B at 3-5 mg/kg daily is an alternative but should be used with caution, particularly with urinary tract involvement 4

Infusion Protocol

Use a dedicated IV line with controlled infusion rate:

• Infuse through a dedicated intravenous line to allow precise control without interference from other medications 1
• Standard infusion time is typically 2 hours, though this can be extended to 6-8 hours if needed for tolerance 2
• Administer 1 liter of normal saline after the infusion in patients who can tolerate fluids to further reduce nephrotoxicity 1, 3

Monitoring During Infusion

Watch closely for infusion-related reactions, especially during initial doses:

• Monitor for chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria 1
• If reactions occur, temporarily interrupt the infusion and administer intravenous diphenhydramine 1
• Infusion-related reactions (fever, chills, rigors) occur in approximately 17-18% of patients receiving liposomal amphotericin B, significantly less than the 44-54% seen with conventional amphotericin B 5

Laboratory Monitoring Throughout Therapy

Regular monitoring is required to detect toxicity:

• Monitor renal function and serum creatinine regularly 1
• Check electrolytes, particularly potassium and magnesium 1
• Monitor liver function tests 1
• Nephrotoxicity (defined as serum creatinine ≥2 times upper limit of normal) occurs in approximately 19% of patients, significantly less than the 34% with conventional amphotericin B 5

Duration of Therapy

Treatment duration depends on the specific infection:

• For candidemia without metastatic complications: 2 weeks after documented clearance from bloodstream 4
• For CNS infections: Continue until all signs, symptoms, CSF abnormalities, and radiological abnormalities resolve 4
• For endophthalmitis: At least 4-6 weeks, with final duration based on repeated ophthalmological examinations 4
• For severe fungal infections with CNS involvement: 4-6 weeks for induction and consolidation phases 2

Special Administration Routes

Alternative routes are used for specific anatomical sites:

Intravitreal Injection (for endophthalmitis with macular involvement)

• Dose: 5-10 μg/0.1 mL sterile water 4, 1
• Used in addition to systemic therapy 4

Intraventricular Administration (through CNS devices)

• Dose: 0.01-0.5 mg in 2 mL of 5% dextrose in water 4, 1
• Only when ventricular device cannot be removed 4

Bladder Irrigation (for urinary candidiasis)

• Dose: 50 mg/L sterile water daily for 5 days 1

Critical Pitfalls to Avoid

Common errors that compromise safety or efficacy:

• Do not exceed 10 mg/kg/day as higher doses increase nephrotoxicity without improving efficacy 6
• Do not use liposomal amphotericin B as first-line in neonates with disseminated candidiasis—conventional amphotericin B deoxycholate is preferred 4
• Do not skip premedication, as this significantly increases infusion-related reactions 1, 3
• Do not mix with other medications in the same IV line 1
• Do not use in patients with urinary tract involvement in neonates without careful consideration, as lipid formulations may be less effective 4

Advantages Over Conventional Amphotericin B

Liposomal formulation provides significant safety benefits:

• Fewer breakthrough fungal infections (3.2% vs 7.8% with conventional amphotericin B) 5
• Significantly reduced nephrotoxicity (19% vs 34%) 5
• Fewer infusion-related reactions (fever 17% vs 44%, chills 18% vs 54%) 5
• Equivalent or superior efficacy for most invasive fungal infections 5, 6
• Can be safely delivered at markedly higher doses (up to 10 mg/kg) when needed 7