An evaluation of hepatotoxicity and nephrotoxicity of liposomal amphotericin B (L-AMB)

J Med Toxicol. 2011 Mar;7(1):12-5. doi: 10.1007/s13181-010-0120-8.

Abstract

Hepatic and renal functions are important considerations when selecting antifungal therapy. This investigation of liposomal amphotericin B (L-AMB) was conducted to determine the incidence and factors associated with the development of hepatotoxicity and nephrotoxicity. A retrospective chart review was conducted of 100 consecutive patients receiving L-AMB at doses of 1, 3, and 5 mg/kg. Hepatotoxicity was defined as an increase of bilirubin greater than 1.5 mg/dl or AST and ALT greater than three times the normal range. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or an increase of 50% from baseline. Patients were included if they were 18 years of age or older. Patients were excluded if they had developed hepatic or renal dysfunction prior to L-AMB administration. Seventy-five patients were included based upon the predefined inclusion/exclusion criteria. Twenty-one percent (16/75) developed hepatotoxicity based upon the predefined criteria. There were no additive correlates for this adverse effect. Overall, 56% (42/75) of patients developed nephrotoxicity. Seventy-four percent (31/42) were exposed to IV contrast, and 90% (38/42) were receiving nephrotoxins concurrently. Age, cumulative dose, concomitant nephrotoxins, and IV contrast exposure were associated with increased nephrotoxicity (p<0.001). The development of hepatotoxicity was observed; however, no correlates (age, dose escalation, or cumulative dose) were significantly associated with its occurrence. Overall nephrotoxicity with L-AMB was common and often multifactorial. Lipid amphotericin B products are associated with lower rates of nephrotoxicity than conventional amphotericin; however, in this analysis, L-AMB was associated with a high incidence of nephrotoxicity.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Amphotericin B / administration & dosage*
  • Amphotericin B / adverse effects*
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects*
  • Bilirubin / urine
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Chemical and Drug Induced Liver Injury / urine
  • Contrast Media / administration & dosage
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Drug Carriers / adverse effects*
  • Humans
  • Incidence
  • Liposomes
  • Middle Aged
  • Renal Insufficiency / blood
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / epidemiology
  • Retrospective Studies

Substances

  • Antifungal Agents
  • Contrast Media
  • Drug Carriers
  • Liposomes
  • Amphotericin B
  • Creatinine
  • Bilirubin