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

• Published in: International journal of antimicrobial agents 2011-11, Vol.38 (5), p.417-420
• Main Authors: Shigemi, Akari, Matsumoto, Kazuaki, Ikawa, Kazuro, Yaji, Keiko, Shimodozono, Yoshihiro, Morikawa, Norifumi, Takeda, Yasuo, Yamada, Katsushi
• Format: Article
• Language: English
• Subjects: adults; adverse effects; Aged; alanine transaminase; amphotericin B; Amphotericin B - administration & dosage; Amphotericin B - adverse effects; Amphotericin B - therapeutic use; Anaemia; anemia; Anemia - chemically induced; Anemia - epidemiology; Anemias. Hemoglobinopathies; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal Agents - administration & dosage; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; aspartate transaminase; bilirubin; Biological and medical sciences; Chemical and Drug Induced Liver Injury - epidemiology; Diseases of red blood cells; dose response; erythrocyte count; erythrocytes; Female; Hematologic and hematopoietic diseases; Hepatotoxicity; Humans; Hypokalaemia; Hypokalemia - chemically induced; Hypokalemia - epidemiology; Infectious Disease; Kidney Diseases - chemically induced; Kidney Diseases - epidemiology; Liposomal amphotericin B; Male; Medical sciences; Middle Aged; Nephrotoxicity; patients; Pharmacology. Drug treatments; Platelet diseases and coagulopathies; probability; safety assessment; Thrombocytopenia; Thrombocytopenia - chemically induced; Thrombocytopenia - epidemiology
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.07.004

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.