Amphotericin B toxicity reduced by administration in fat emulsion

Ann Pharmacother. 1995 May;29(5):496-500. doi: 10.1177/106002809502900509.

Abstract

Objective: To report a patient with intolerance to amphotericin B reversed by preparing the antifungal in fat emulsion 20% and to review the medical literature on innovative formulations of amphotericin B.

Case summary: A 51-year-old man diagnosed with acute myelogenous leukemia was treated with standard induction chemotherapy. Empiric antibiotic therapy was initiated 2 days postchemotherapy; however, the patient continued to be febrile until day 7. At this time amphotericin B 35 mg/250 mL D5W over 4 hours was administered. Despite premedication, the patient experienced severe rigors, chills, and fever. As the result of continuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusion-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsion 20% was administered over 2 hours after patient consent was obtained. Premedication was administered and the patient tolerated therapy without adverse events. Amphotericin B dosage escalations to 50 and 70 mg were tolerated similarly. During this treatment the patient became afebrile and the serum creatinine concentration decreased to normal.

Discussion: Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the empiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents characteristically prescribed in these patients. Furthermore, infusion-related events, if not intolerable, can dramatically reduce the patient's quality of life. For these reasons, novel means of amphotericin B administration are being explored.

Conclusions: The delivery of amphotericin B in a lipid diluent may have substantial benefit in reducing the nephrotoxicity and infusion-related events associated with the antifungal. Prospective clinical trial comparing lipid-complexed amphotericin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects*
  • Amphotericin B / therapeutic use
  • Drug Interactions
  • Fat Emulsions, Intravenous / administration & dosage*
  • Fat Emulsions, Intravenous / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Leukemia, Myeloid, Acute / drug therapy
  • Male
  • Middle Aged

Substances

  • Fat Emulsions, Intravenous
  • Amphotericin B