Lipid Formulations of Amphotericin B: Clinical Efficacy and Toxicities

Abstract

Commercially available lipid formulations of amphotericin B (Abelcet, Amphotec, and AmBisome) represent a significant advance in drug delivery technology. Differences in biochemical, pharmacokinetic, and pharmacodynamic properties among the lipid products have been shown in in vitro and in vivo models. Clinical experience with these products has been primarily in patients either refractory to or intolerant of conventional amphotericin B deoxycholate (AmBd). None of the lipid-based products demonstrates superior efficacy when prospectively compared with AmBd in the treatment of documented infections. When used for the empirical treatment of febrile neutropenia, AmBisome significantly reduced the incidence of proven emergent fungal infections but did not improve short-term survival rates, in comparison with AmBd. Acute infusion-related adverse events vary, whereas nephrotoxicity is reduced with all three lipid formulations. Until superior efficacy is clearly shown (for documented infections) or pharmacoeconomic analyses document the value of these drugs, use of such expensive agents should be highly restricted to those who are intolerant of or refractory to AmBd.

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

“…20 Lipid-based amphotericin B products have been associated with a decreased incidence of nephrotoxicity compared with amphotericin B. 33,35 The results of the current study support this finding, with no ABLCtreated or L-AmB-treated patients developing Grade 3 or 4 nephrotoxicity. Moderately severe-to-severe hyperbilirubinemia, which also has been reported with ABLC and L-AmB, was rare and occurred in both treatment groups.…”

“…Moderately severe-to-severe hyperbilirubinemia, which also has been reported with ABLC and L-AmB, was rare and occurred in both treatment groups. 35 Another noteworthy finding of the current study was the similar overall mortality rates in patients who received ABLC and patients who received L-AmB (8% and 10%, respectively). Fungal infection-related deaths were uncommon, occurring in only 2.3% and 1.4% of ABLC-treated and L-AmB-treated patients, respectively.…”

“…33 This more rapid removal of ABLC compared with L-AmB may result in the release of proinflammatory cytokines from the engulfing macrophages and an increased incidence of infusion-related toxicities. 34,35 The study results show, however, that no statistically significant difference in the incidence of Grade 3 and 4 infusionrelated toxicities was observed in patients who received ABLC or L-AmB (4% and 7%, respectively). This incidence of infusion-related toxicities is similar to the incidence reported in a randomized study comparing ABLC and L-AmB as treatment of suspected or documented fungal infections in adult patients with leukemia (2% and 5%, respectively).…”

Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

“…Since the 1950s, deoxycholate amphotericin B (AmB) has been the main therapeutic agent for fungal infections; however, it is associated with significant toxicities that limit its use, including infusionrelated reactions, nephrotoxicity, hypokalemia, and hepatotoxicity [1]. Lipid formulations of AmB have been developed to improve tolerability while maintaining or even improving the efficacy profile of conventional amphotericin by allowing higher doses [2][3][4][5]. AmB lipid complex (ABLC) injection (Abelcet; The Liposome Company, Princeton, NJ, USA) was the first lipid-based formulation approved by the Federal Drug Administration (FDA) in the USA (in December 1995).…”

Effectiveness of amphotericin B lipid complex (ABLC) treatment in allogeneic hematopoietic cell transplant (HCT) recipients with invasive aspergillosis (IA)

“…These results confirm previous findings that ABLC is superior to AmB in terms of effects on renal function. 20,21 There was no antagonism between antifungal agents when ABLC was started concomitantly with, or sequentially after, itraconazole therapy. 22 Interestingly however, none of seven patients responded when itraconazole was continued after ABLC was started.…”