AmBisome (amphotericin B)


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

Liposomal amphotericin B twice weekly as antifungal prophylaxis in pediatric hematologic malignancy patients.  Bochennek K, Tramsen L. Schedler N, Becker M, Klingebiel T, Groll AH, Lehrnbecher T. Clin Microbiol Infect, Feb. 2011.

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. 

Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety.
Hamill RJ, Sobel JD, El-Sadr W, Johnson PC, Graybill JR, Javaly K, Barker DE. Clin Infect Dis. 2010 Jul 15;51(2):225-32.

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.

Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis.
Sun HY, Alexander BD, Lortholary O, Dromer F, Forrest GN, Lyon GM, Somani J, Gupta KL, del Busto R, Pruett TL, Sifri CD, Limaye AP, John GT, Klintmalm GB, Pursell K, Stosor V, Morris MI, Dowdy LA, Munoz P, Kalil AC, Garcia-Diaz J, Orloff S, House AA, Houston S, Wray D, Huprikar S, Johnson LB, Humar A, Razonable RR, Husain S, Singh N. Clin Infect Dis. 2009 Dec 1;49(11):1721-8.

Employment of lipid formulations of amphotericn B significantly improved 90-day mortality in solid organ transplant recipients with central nervous system cryptococcosis.

Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Rijnders BJ, Cornelissen JJ, Slobbe L, Becker MJ, Doorduijn JK, Hop WC, Ruijgrok EJ, Löwenberg B, Vulto A, Lugtenburg PJ, de Marie S. Clin Infect Dis. 2008 May 1;46(9):1401-8.

Prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of invasive pulmonary aspergillosis in patients with prolonged neutropenia.

Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin. Raad II, Hanna HA, Boktour M, Jiang Y, Torres HA, Afif C, Kontoyiannis DP, Hachem RY.Leukemia. 2008 Mar;22(3):496-503. Epub 2007 Dec 20.

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.

Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Cornely OA, Maertens J, Bresnik M, Ebrahimi R, Ullmann AJ, Bouza E, Heussel CP, Lortholary O, Rieger C, Boehme A, Aoun M, Horst HA, Thiebaut A, Ruhnke M, Reichert D, Vianelli N, Krause SW, Olavarria E, Herbrecht R; AmBiLoad Trial Study Group. Clin Infect Dis. 2007 May 15;44(10):1289-97.

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.

Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial). Caillot D, Thiébaut A, Herbrecht R, de Botton S, Pigneux A, Bernard F, Larché J, Monchecourt F, Alfandari S, Mahi L. Cancer. 2007 Dec 15;110(12):2740-6..

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

New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Sundar S, Rai M, Chakravarty J, Agarwal D, Agrawal N, Vaillant M, Olliaro P, Murray HW.Clin Infect Dis. 2008 Oct 15;47(8):1000-6.

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

Clinical Roundtable Monograph: Lipid-based Amphotericin B Formulations in Opportunistic Infections
Lass-Florl C, Singh N, Knezovic I. Lipid-based amphotericin B formulations in opportunistic infections. Clin Adv Hematol Oncol. 2010; 8: 1-8.

Updated epidemiology and applications of lipid-based amphotericin B formulations of zygomycetes, cryptococcus and leishmania were discussed in this monograph.

Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Moen MD, Lyseng-Williamson KA, Scott LJ. Drugs. 2009;69(3):361-92.

Studies regarding applications of liposomal amphotericin B in febrile neutropenia and invasive fungal infections were extensively reviewed.

Immunocompromised hosts: immunopharmacology of modern antifungals. Ben-Ami R, Lewis RE, Kontoyiannis DP. Clin Infect Dis. 2008 Jul 15;47(2):226-35.

An intriguing discussion of the anti-inflammatory properties of the liposomes of liposomal amphotericin B.

Liposomal amphotericin B: what is its role in 2008? Lanternier F, Lortholary O. Clin Microbiol Infect. 2008 May;14 Suppl 4:71-83.

Detailed description of the unique properties of liposomal amphotericin B in the modern antifungal era.

Amphotericin B lipid preparations: what are the differences? Adler-Moore JP, Proffitt RT. Clin Microbiol Infect. 2008 May;14 Suppl 4:25-36.

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