An evaluation of hepatotoxicity and nephrotoxicity of liposomal amphotericin B (L-AMB).
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.
Medical Intensive Care Unit, Department of Pharmacology, Division of Pulmonary and Critical Care Medicine, RUSH University Medical Center, 1653 West Congress Parkway, Jelke 297, Chicago, IL 60612, USA. Gourang_p_patel@rush.edu
Gourang P
GP
Patel
Christopher W
CW
Crank
Jerrold B
JB
Leikin
D000328:Adult; D000367:Age Factors; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects*; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001663:Bilirubin / Q000652:urine; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000652:urine; D003287:Contrast Media / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008081:Liposomes; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies
D000935:Antifungal Agents; D003287:Contrast Media; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B; D003404:Creatinine; D001663:Bilirubin