Amphotericin B lipid complex for the treatment of invasive fungal infections

Abstract

Amphotericin B lipid complex (ABLC; Abelcet®, Enzon Pharmaceuticals) has become the dominant marketed lipid amphotericin B compound to emerge since the approval of these agents from the mid-1990s onwards. This agent is a 1:1 combination of amphotericin B and a lipid moiety consisting of dimyristoyl phosphatidylcholine and dimyrisoyl phosphatidylcholine, which exists in a ribbon-like molecular structure. ABLC undergoes rapid reticuloendothelial uptake from the circulation and achieves significantly higher tissue concentrations in the liver, spleen and lung compared to comparably dosed conventional amphotericin B. ABLC is approved by the FDA for all mycoses in amphotericin B-intolerant or -refractory infection. Randomised, controlled trials of amphotericin B have shown comparable efficacy in candidiasis and an improved outcome in invasive aspergillosis versus historical controls. ABLC has demonstrated a reduced incidence of nephrotoxicity and infusion reactions versus amphotericin B. Comparative studies against other lipid formulations are quite limited and have shown variable differences in infusion toxicity, nephrotoxicity, hepatotoxicity and clinical efficacy. Postapproval experience has shown substantial efficacy for less common mycotic pathogens including zygomycosis. The precise position of ABLC versus both other lipid formulations and expanding formulary of new antifungal agents is in flux. Future studies which examine its clinical efficacy, role in combination therapy, toxicity and cost-effectiveness in these complex patients are needed.