Infusion-related events amphotericin

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

The safety and efficacy of ABLC 5 mg/kg/day in patients with neutropenia and intolerance or refractoriness to amphotericin deoxycholate have been reported in two smaller series of 25 treatment courses from the UK. In one, the mean serum creatinine at the start of therapy was 139 pmol/l and at the end of therapy 132 pmol/l there were no infusion-related adverse events (27). There was an increase in alanine transaminase activity in 12 of the 22 analysed treatment courses. In the other, there was an increase in serum creatinine in 5 of 18 courses (28%), and hypokalemia (less than 2.5 mmol/1) in two courses (11%) premedication for infusion-associated reactions was required in three courses (17%) (28). There were modest increases in serum alanine transaminase activities in five patients (30%). 

Liposomal amphotericin and ABLC have been compared in an open randomized study in 75 adults with leukemia and 82 episodes of suspected or documented mycosis (48). The median durations of treatment and dosages were 15 days at 4 mg/kg/day for liposomal amphotericin and 10 days at 3 mg/kg/day for ABLC. Acute but not dose-limiting infusion-related adverse events occurred in 36 versus 70%. Bilirubin increased to over 1.5 times baseline in 59 versus 38%. There was no difference in the effects of either agent on renal function and drug-related withdrawals. The overall response rate to therapy in documented fungal infections (29 and 30% respectively) was not different between the two drugs. 

Anaphylaxis after ABCD occurred in a patient who had previously been treated with both amphotericin deoxycholate and ABLC without infusion-related adverse effects (65). During the first infusion of ABCD he developed spontaneously reversible severe back pain and then swelling of his lips, respiratory distress, and left-sided hemipar-esis, which resolved after 24 hours. An MRI scan suggested an ischemic event in the right putamen, lending support to the hypothesis that he had had an anaphylactic reaction to ABCD, hypoperfusion, and a subsequent stroke. 

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