Administration Protocol for Lyophilized Amphotericin B

Administration Guidelines

Pre-medication with diphenhydramine or acetaminophen is recommended to reduce infusion-related reactions, and 1 L of normal saline should be administered before and after infusion to reduce nephrotoxicity in patients who can tolerate fluids 1, 2

The Infectious Diseases Society of America recommends dosing conventional amphotericin B deoxycholate at 0.5-1.5 mg/kg/day IV for standard infections, and 0.7-1.0 mg/kg/day for severe or life-threatening infections 3, 4
For lipid formulations, the recommended dosing is:

For intravitreal injection, a dose of 5-10 μg/0.1 mL sterile water is recommended 5, 6
For intraventricular administration through CNS devices, a dose of 0.01-0.5 mg in 2 mL 5% dextrose in water is recommended 5
For bladder irrigation, a dose of 50 mg/L sterile water daily for 5 days is recommended 5

Regular monitoring of renal function, electrolytes, and liver function tests is recommended 4
Patients should be watched for infusion-related reactions including fever, chills, nausea, and vomiting 4
For persistent fungal infections despite therapy, investigation for deep tissue focus of infection is recommended 4

For cryptococcal meningitis, the recommended dose is 4-6 mg/kg daily, as suggested by the MMWR Recommendations and Reports 7
For children with cryptococcal meningitis, the recommended dose is 2 mg/kg daily, with doses up to 7.5 mg/kg daily for refractory cases, according to the MMWR Recommendations and Reports 8
The Centers for Disease Control and Prevention, as reported in MMWR Recommendations and Reports, recommend monitoring for infusion-related reactions, including chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria, and temporarily interrupting the infusion and administering intravenous diphenhydramine if reactions occur 8

For patients with renal impairment, the Infectious Diseases Society of America, as published in Clinical Infectious Diseases, recommends using AmBisome over conventional amphotericin B due to its significantly less nephrotoxicity 9

A dedicated line allows precise control of infusion rate without interference from other medications that may have different infusion requirements, as recommended by the Infectious Diseases Society of America 10

The separate line principle applies to all amphotericin B formulations, although lipid formulations may have different compatibility requirements, according to the Clinical Infectious Diseases guidelines 11

The Centers for Disease Control and Prevention, as reported by MMWR Recommendations and Reports, recommends reserving glucocorticosteroids for rare cases where severe infusion-related reactions occur despite standard premedication with diphenhydramine and acetaminophen 12
The MMWR Recommendations and Reports suggests administering glucocorticosteroids approximately 30 minutes before the infusion if needed 12
Consider adding hydrocortisone for subsequent infusions only if reactions were severe, as recommended by MMWR Recommendations and Reports 12

Adults with candidemia, invasive candidiasis, aspergillosis, or other systemic fungal infections should receive 3–5 mg/kg IV once daily (Infectious Diseases Society of America guideline) [13][14].

CNS fungal infections (meningitis, brain abscess) are treated with 5–10 mg/kg IV once daily (IDSA) [13][14].
Cryptococcal meningitis: 5 mg/kg IV daily, with optional flucytosine 25 mg/kg every 6 h (IDSA) [13][14].
Adding flucytosine 25 mg/kg q6h is recommended to enhance efficacy for CNS infections (IDSA) [13][14].

Systemic therapy: 3–5 mg/kg IV daily, with or without oral flucytosine (IDSA) [13][14].
Adjunctive intravitreal injection may be required for macular involvement (IDSA) [13][14].

First‑line therapy for disseminated candidiasis in neonates is conventional amphotericin B deoxycholate 1 mg/kg/day (IDSA) 15.
Liposomal amphotericin B 3–5 mg/kg daily is an alternative but should be used cautiously, especially with urinary‑tract involvement (IDSA) 15.
Liposomal amphotericin B should not be used as first‑line in neonates; conventional formulation is preferred (IDSA) 15.
When used in neonates with urinary‑tract infection, careful consideration is required because lipid formulations may be less effective (IDSA) 15.

Candidemia without metastatic complications: treat for 2 weeks after documented blood‑culture clearance (IDSA) 15.
CNS infections: continue therapy until clinical signs, CSF parameters, and radiologic abnormalities have resolved (IDSA) [13][14].
Endophthalmitis: minimum 4–6 weeks, guided by serial ophthalmologic examinations (IDSA) [13][14].

Intravitreal injection for endophthalmitis – 5–10 µg in 0.1 mL sterile water, administered in addition to systemic therapy (IDSA) 13.
Intraventricular administration (when ventricular device cannot be removed) – 0.01–0.5 mg diluted in 2 mL 5 % dextrose in water (IDSA) 13.

Maximum recommended dose is 10 mg/kg/day; higher doses increase nephrotoxicity without added efficacy (IDSA) 15.

Once‑daily administration is the standard schedule for all liposomal amphotericin B formulations and indications, including doses of 3 mg/kg, 5 mg/kg, and up to 10 mg/kg for central nervous system involvement. 16

For severe systemic fungal infections without CNS involvement, the recommended dose is 3–5 mg/kg per day. 17
In COVID‑19‑associated mucormycosis (non‑CNS disease), a dose of 5 mg/kg per day is advised. 16
For sporotrichosis and other disseminated fungal infections, the standard dosing remains 3–5 mg/kg per day. 18

When escalating from 3 mg/kg to 5 mg/kg, the 24‑hour dosing interval should be preserved; the higher dose does not require more frequent administration. 16
Even at the maximum recommended dose of 10 mg/kg per day for CNS infections, the medication is still given once daily. 16

Administer the 5 mg/kg dose exactly 24 hours after the prior 3 mg/kg dose (e.g., at 13:00) and continue daily dosing at the same clock time to maintain therapeutic drug levels while minimizing nephrotoxicity. 16
Premedicate with diphenhydramine or acetaminophen 30 minutes before the infusion to reduce infusion‑related reactions. 16
Give 1 L of normal saline before and after the infusion, provided the patient can tolerate the fluid volume, to lessen the risk of nephrotoxicity. 16

In patients receiving liposomal amphotericin B, the development of renal toxicity—identified by a clinically significant rise in serum creatinine—should prompt modification of therapy by either switching to a lipid formulation (if not already used) or reducing the amphotericin B dose, when clinically feasible, to limit further kidney injury. 19