How high dose of amphotericin B (AmBisome) could be given to a 5.5 months old infant weighing 7.5 k

Fråga: How high dose of amphotericin B (AmBisome) could be given to a 5.5 months old infant weighing 7.5 kg?

Sammanfattning: In studies where liposomal amphotericin B has been given to neonates the doses has been in the range between 1 mg/kg up to 3 mg/kg, although a few cases of doses up to 5 and 6 mg/kg are described. Since 1-3 mg/kg is also the recommended dose according to FASS to avoid nephrotoxicity we suggest to give the infant a dose of 3 mg/kg bodyweight.

Svar: According to Fass infants from 1 months of age could be given liposomal amphotericin B (AmBisome) in the same dosage regime as adults. The normal dose is 1-3 mg/kg body weight.

Nephrotoxicity is a well-known adverse drug reaction to Amphotericin B. However, studies have shown that children are less likely to develop nephrotoxicity with a lipid preparation of amphotericine B, such as AmBiosome, compared with conventional amphotericin B (2). For liposomal amphotericine, doses from 5 mg/ kg and above have been associated with a markedly increased risk of nephrotoxicity (1).

In a study of 21 newborn with very low birth weight (<1.5 kg) and candida infection liposomal amphotericin B was given in an average dose of 2.6 mg/kg/day and the maximal dosage ever given was 5 mg/kg/day (3). No cases of nephrothoxicity were reported in this study.

In a study in immunosuppressed children between 1.8-16 years of age liposomal amphotericin B was given to 5 children in an initial dose of 0.5-3 mg/kg. The dose was later increased to 4-6 mg/kg. In one of the 5 children creatinine rise of 66% occurred during concomitant treatment with cyclosporine A (4).

In a retrospective study on neonates that had received amphotericin B deoxycholate, i.e. not the lipid preparation, the average dosage of amphotericine was 0.9 mg/ kg (n=92). In this study 16% of the neonates (n=15) developed symptoms of nephrotoxicity. There was no difference between the average amphotericin B doses among the neonates developing renal impairment compared with the ones tolerating amphotericin; 0.8 mg/ kg compared to 0.9 mg/kg (5).

Alternative treatments to amphotericine B for treating aspergillus infections could be caspofungin or voriconazol although the experiences of these drugs in treatment of children <12 months of age are limited (1). FASS 2010 Blyth et al, Cochrane Database System Rev 2010 Weitkamp JH, Poets CF, Sievers R, Musswessels E, Groneck P, Thomas P et al. Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome). Infection 1998;26(1):11-15 Zoubek A, Emminger W, Emminger-Schmidmeier W, Peters C, Pracher E, Grois N et al. Conventional vs. liposomal amphotericin B in immunosuppressed children. Pediatr Hematol Oncol 1992;9(2):187-190 Le J, Adler-Shohet FC, Nguyen C, Lieberman JM. Nephrotoxicity associated with amphotericin B deoxycholate in neonates. Pediatr Infect Dis J 2009;28(12):1061-1063