OPEN IN READ APP
COMPARATIVE STUDY
JOURNAL ARTICLE
REVIEW

Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability

M Tiphine, V Letscher-Bru, R Herbrecht
Transplant Infectious Disease: An Official Journal of the Transplantation Society 1999, 1 (4): 273-83
11428998
Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%. Moreover, amB is toxic, especially for the kidneys. New formulations have been developed in an attempt to improve both efficacy and tolerability. In an attempt to reduce toxicity, a number of investigators have reconstituted amB in a lipid emulsion, but few data are available on efficacy in documented infections. An improvement in immediate and renal tolerance was obtained with equivalent daily dose regimens, but the therapeutic index does not appear to be improved. This approach cannot be recommended at present. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (AmBisome). The efficacy of ABCD on various fungal infections has been assessed in open trials, with a response rate of 49% in aspergillosis, 70% in candidiasis, and 67% in mucormycosis. In two randomized trials comparing ABCD with amB in invasive aspergillosis and in persistent febrile neutropenia, the response rates were equivalent. ABCD was less nephrotoxic. In contrast, immediate reactions to ABCD were as frequent and severe as with amB. These immediate effects are more frequent during the first infusions and lessen as treatment continues. The recommended dose is 3-4 mg/kg/day. ABLC appeared to be effective as rescue therapy in various types of invasive mycoses, with a response rate of 42% in aspergillosis, 67% in candidiasis, and 82% in fusariosis. Efficacy identical to that of amB was demonstrated in a comparative randomized trial involving patients with invasive candidiasis. General and renal tolerability is improved compared with amB. The recommended dose regimen is 5 mg/kg/day. Liposomal amB (AmBisome) is the only truly liposomal formulation. The response rates in preliminary trials were 66% in aspergillosis and 81% in candidiasis. Several comparative studies have confirmed that this formulation has similar or superior efficacy relative to amB in various fungal infections and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. The optimal dosing remains unclear but is generally between 3 and 5 mg/kg/day. A double-blind trial comparing the tolerance of liposomal amB and ABLC demonstrated that both infusion-related events and nephrotoxicity were significantly lower for liposomal amB. In sum, the new lipid formulations of amB are effective in various invasive fungal infections. The three formulations exhibit reduced nephrotoxicity compared with conventional amB. Large-scale comparative clinical trials may clarify issues of relative efficacy in various forms of mycotic infections.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
11428998
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"