Comparison: Amphotericin B Formulations

Conventional	Lipid Base
amphotericin B deoxycholate       [available in HKGU]	amphotericin B lipid complex (ABLC, Abelcet),       amphotericin B cholesteryl sulfate complex (amphotericin B colloidal dispersion, ABCD, Amphotec)       liposomal amphotericin B (AmBisome)

•  Amphotericin B has the broadest spectrum of activity of any antifungal agent. For decades it has been considered the gold standard for the treatment of severe systemic fungal infections.
• However, the efficacy of the conventional formulation, amphotericin B deoxycholate, is outweighed by a significant toxicity profile, often leading to severe renal damage.
• Adverse infusion-related events are also of concern, sometimes resulting in discontinuation of therapy

Safety and Efficacy

Amphotericin B deoxycholate

• Infusion-related reactions, particularly nausea and vomiting, are common with amphotericin B deoxycholate administration.
• Drug-induced fever, chills, and headache can also be seen.
• Medications can be given prior to amphotericin B administration to minimize or prevent these adverse effects
• With amphotericin B deoxycholate, a reversible and often transient decline in glomerular filtration rate (GFR) has been described. Volume expansion with intravenous sodium chloride (a practice commonly known as "sodium loading") may ameliorate the decline in GFR; 500 mL of 0.9 percent sodium chloride is typically given prior to the amphotericin B infusion

Lipid Soluble Amp B

• Liposomal amphotericin B has a lower incidence of infusion-related reactions than amphotericin B deoxycholate.
• However, there is a unique group of infusion reactions that can occur with liposomal amphotericin B. These include chest pain, dyspnea, hypoxia, abdominal pain, flushing, and urticaria and generally respond to therapy with diphenhydramine
• Infusion-related intolerance to one formulation may not predict similar reactions to other formulations. As an example, ABLC administration was uneventful in 34 of 40 patients (85 percent) who had previous severe reactions to liposomal amphotericin B in one retrospective study
• Electrolyte abnormalities, such as hypokalemia, hypomagnesemia, and hyperchloremic acidosis, may occur following the administration of both lipid-based and deoxycholate formulations of amphotericin B
• Nephrotoxicity of ABLC is often very modest and can be reversed rapidly after ABLC is discontinued. However, patients who receive other nephrotoxic agents or who have other renal disorders can sometimes become azotemic quite rapidly when they are treated with ABLC

Recommendations:

• For the treatment of most invasive fungal infections, an amphotericin B lipid formulation provides a safer alternative than conventional amphotericin B, with at least equivalent efficacy
• Judgments about the preferred formulation for empirical treatment should be made on the basis of several factors, including the clinical characteristics of the patient and the morbidity and costs associated with therapeutic options

References:

1. www.uptodate.com
2. A drug use evaluation of amphotericin B lipid complex injection following institution of new treatment guidelines at a tertiary teaching medical center
3. http://cid.oxfordjournals.org/content/31/5/1164.full