Commentary
Liposomal amphotericin B comprises spherical unilamellar liposomes which
are composed of hydrogenated soy phosphatidylcholine, cholesterol,
distearoyl-phophatidylglycerol and amphoterin B. Its FDA indications include
1) empirical therapy for presumed fungal infection in febrile, neutropenic
patients; 2) treatment of cryptococcal meningitis in HIV-infected patients;
3) treatment of patients with Aspergillus species, Candida species
and/or Cryptococcus species infections refractory to amphotericin B
deoxycholate, or in patients where renal impairment or unacceptable toxicity
precludes the use of amphotericin B deoxycholate; 4) treatment of visceral
leishmaniasis.
Liposomal amphotericin B is active against Aspergillus spp. except for some
isolates of Aspergillus terreus, Candida spp. except for Candida lusitaniae,
Cryptococcus neoformans, Blastomyces dermatitidis, Pseudallescheria boydii,
Malassezia furfur, Fusarium spp., and zygomycetes. Liposomal amphotericin B
is not active against Trichosporon beigelii.
Compared with other lipid formulations of amphotericin B, liposomal
amphotericin B has significantly less nephrotoxicity, fewer infusion-related
side effects, and better brain penetration than other lipid formulations.
Thus, it can be used safely and repeatedly at high doses to treat brain and
other difficult-to-treat infections, such as zygomycosis. However, it is
also the most expensive agent among all the lipid formulations of
amphotericin B.
Anaphylaxis has been reported in all amphotericin B preparations, including
liposomal amphotericin B. Nevertheless, liposomal amphotericin B has a lower
incidence of infusion-related reactions, hypokalemia, and various events
related to decreased renal function than amphotericin B deoxycholate.
liposomal amphotericin B has the potential to increase digitalis toxicity
and enhance curariform effect of skeletal muscle relaxants due to
amphotericin-induced hypokalemia, results in additive nephrotoxicity when
other nephrotoxic agents are co-administered, and leads to additive
hypokalemia with concurrent diuretic use.
Clinical Studies
Invasive Fungal Infection
Systemic antifungal prophylaxis with liposomal amphotericin B 2.5 mg/kg twice weekly is feasible, safe and seems to be an effective approach for antifungal prophylaxis in high-risk pediatric cancer patients.
Liposomal amphotericin B demonstrated similar efficacy in the treatment of cryptococcal meningitis in HIV-positive patients as amphotericin B deoxycholate; a dose of 3 mg/kg/day was associated with significantly fewer adverse effects than a dose 6 mg/kg/day.
Employment of lipid formulations of amphotericn B significantly improved 90-day mortality in solid organ transplant recipients with central nervous system cryptococcosis.
Prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of invasive pulmonary aspergillosis in patients with prolonged neutropenia.
Salvage therapy of invasive aspergillosis with posaconazole demonstrated greater efficacy and safety than that with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin.
Favorable responses and survival rates at 12 weeks were similar between patients with invasive mold infection receiving high-loading dose regimen and standard dosing while higher rates of nephrotoxicity in those receiving high-loading dose regimen.
Patients with invasive aspergillosis receiving combination therapy with liposomal amphotericin B and caspofunging at the standard dose have significantly more favorable overall responses of than those treated with monotherapy with high-dose liposomal amphotericin B.
Visceral leishmaniasis
The cure rates of visceral leishmaniasis at 9 months post-treatment were similar in patients receiving liposomal amphotericin B for 15 days and those receiving single-dose liposomal amphotericin B (5 mg/kg or 3.75 mg/kg) followed by miltefosine for 10 or 14 days.
Review Articles
Updated epidemiology and applications of lipid-based amphotericin B formulations of zygomycetes, cryptococcus and leishmania were discussed in this monograph.
Studies regarding applications of liposomal amphotericin B in febrile neutropenia and invasive fungal infections were extensively reviewed.
An intriguing discussion of the anti-inflammatory properties of the liposomes of liposomal amphotericin B.
Detailed description of the unique properties of liposomal amphotericin B in the modern antifungal era.
Comprehensive comparisons among different lipid formulations of amphotericin B, primarily liposomal amphotercin B and amphotericin B lipid complex.
Adverse Drug Reactions and Warnings
FDA Information
Manufacturer/Distributor Product Information