Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B

Expert Opin Drug Saf. 2013 Nov;12(6):881-95. doi: 10.1517/14740338.2013.827168. Epub 2013 Aug 10.

Abstract

Introduction: Amphotericin B (AmB) was first approved by the US Food and Drug Administration in 1959 with sodium deoxycholate (DAmB, Fungizone®). Extensive toxicities associated with the drug led to the development of lipid formulations of AmB, including liposomal amphotericin B (L-AmB, AmBisome®). Phase I studies as well as comparative Phase III clinical trials indicate that L-AmB is associated with less nephrotoxicity and reduced infusion-related toxicity. There is, however, no recent comprehensive review of the safety and tolerability of L-AmB.

Areas covered: This article reviews the safety, tolerability and the mechanisms of the major toxicities associated with L-AmB, including nephrotoxicity, infusion-related reactions (IRRs), anemia and thrombocytopenia, and hepatic abnormalities. The article further discusses the mechanism of action and pharmacokinetics of L-AmB.

Expert opinion: L-AmB is a broad-spectrum antifungal agent that has significantly reduced toxicities compared to its predecessor, DAmB.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphotericin B / adverse effects*
  • Amphotericin B / pharmacokinetics
  • Amphotericin B / pharmacology
  • Animals
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology
  • Clinical Trials as Topic
  • Drug Approval
  • Humans
  • Mycoses / drug therapy
  • United States
  • United States Food and Drug Administration

Substances

  • Antifungal Agents
  • liposomal amphotericin B
  • Amphotericin B