Safety analysis of liposomal amphotericin B in adult patients: anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia

Int J Antimicrob Agents. 2011 Nov;38(5):417-20. doi: 10.1016/j.ijantimicag.2011.07.004. Epub 2011 Aug 31.

Abstract

Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has been shown to have a better safety profile than both the deoxycholate and lipid complex forms of amphotericin B; however, the frequency of major side effects is still unclear. Thus, the aim of the present study was to assess retrospectively the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia as well as the relationship between daily dose of L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre-treatment) and anaemia were observed in 7 and 10 of 21 adult patients, respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of L-AmB that are estimated to cause side effects of a low RBC count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day, respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of total bilirubin, γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7, 8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9 patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not caused in a dose-dependent manner. In conclusion, the present analyses showed that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult patients. It is important to pay attention to causing anaemia and thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and >3.0mg/kg/day, respectively.

MeSH terms

  • Aged
  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects*
  • Amphotericin B / therapeutic use
  • Anemia / chemically induced
  • Anemia / epidemiology*
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / therapeutic use
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Female
  • Humans
  • Hypokalemia / chemically induced
  • Hypokalemia / epidemiology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / epidemiology
  • Male
  • Middle Aged
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / epidemiology*

Substances

  • Antifungal Agents
  • liposomal amphotericin B
  • Amphotericin B