Amphotericin B Formulations
GENERAL PRINCIPLES
Amphotericin B is fungicidal by interacting with ergosterol and disrupting the fungal cell membrane. Reformulation of this agent in various lipid vehicles has decreased some of its adverse side effects.
Amphotericin B formulations are not effective for Pseudallescheria boydii, Candida Iusitaniae, or Aspergillus terreus infections.TREATMENT
• Amphotericin B deoxycholate (0.3-1.5 mg/kg q24h as a single infusion over 2-6 h) was once widely used but has now been supplanted by lipid-based formulations of the drug as a result of their improved tolerability.
• Lipid complexed preparations of amphotericin B, including liposomal amphotericin B (LAmB; 3-6 mg/kg IV q24h) and amphotericin B lipid complex (5 mg/kg IV q24h), have decreased nephrotoxicity and are generally associated with fewer infusion-related reactions than amphotericin B deoxycholate. LAmB has the most FDA-approved uses and appears to be the best tolerated lipid amphotericin B formulation overall.
SPECIAL CONSIDERATIONS
• The major adverse event of all amphotericin B formulations, including the lipid formulations, is nephrotoxicity. Patients should receive 500 mL of normal saline before and after each infusion to minimize nephrotoxicity. Concomitant administration of other nephrotoxins should be avoided if possible.
• Common infusion-related effects include fever/chills, nausea, headache, and myalgias. Premedication with 500-1000 mg of acetaminophen and 50 mg of diphenhydramine may control many of these symptoms. More severe reactions may be prevented by premedication with hydrocortisone 25-50 mg IV. Intolerable infusion-related chills can be managed with meperidine 25-50 mg IV.
• Amphotericin B therapy is associated with potassium and magnesium wasting that generally requires supplementation. Serum creatinine and electrolytes (including Mg2+ and K+) should be monitored at least two to three times a week.