Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations

Abstract

Aims: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children.

Methods: Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity.

Results: Seventy-six children received c-amB and 39 received l-amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion-related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l-amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB 3.1 vs. l-amB 2.3 mmol kg^-1 d^-1 ; P = 0.29). Hepatotoxicity occurred more frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032).

Conclusions: When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.

Keywords: Amphotericin-B; adverse effects; antifungal; liposomal; paediatric.