Lipid formulations of amphotericin B: clinical efficacy and toxicities

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.