title: Safety analysis of liposomal amphotericin B in adult patients: anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia.
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.
authors: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors: Akari
authors: A
authors: Shigemi
authors: Kazuaki
authors: K
authors: Matsumoto
authors: Kazuro
authors: K
authors: Ikawa
authors: Keiko
authors: K
authors: Yaji
authors: Yoshihiro
authors: Y
authors: Shimodozono
authors: Norifumi
authors: N
authors: Morikawa
authors: Yasuo
authors: Y
authors: Takeda
authors: Katsushi
authors: K
authors: Yamada
mesh_terms: D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B