NAPLEX Question of the Week: Fungus Among Us!

Antifungal therapy is an important component of drug therapy. Today's question focuses on the one and only Amphotericin.
NAPLEX Question of the Week: Fungus Among Us!

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AmBisome or Amphotericin B liposomal formulation is an IV agent used in the treatment of various fungal infections. Which of the following statements regarding AmBisome is true? Select all that apply.


A. AmBisome 50 mg vials must be reconstituted with sterile water for injection (SWFI) and then further diluted in dextrose

B. AmBisome must be filtered using a 5-micron filter when injecting the reconstituted drug into the final diluent bag

C. When administering AmBisome, the patients IV line should be flushed with D5W after administering the drug

D. Incidence of nephrotoxicity and infusion related events with AmBisome are higher than with Fungizone (deoxycholate formulation)

E. There are no recommended dosage adjustments in renal or hepatic impairment for AmBisome administration


Answer with rationale:

The correct answers are A, B, C, and E.

Amphotericin B is an antifungal used to treat a wide variety of fungal pathogens. Its antifungal effects come from disruption of the fungal cell wall due to the drug’s ability to bind ergosterol, leading to pores and leakage.  Because amphotericin B is associated with significant toxicities such as nephrotoxicity, fever, chills, nausea and vomiting, it is usually reserved for patients who have severe, life-threatening invasive fungal infections or cannot tolerate other antifungal options, such as voriconazole. Patients who exhibit infusion related reactions when receiving any form of amphotericin B can be pretreated with acetaminophen, diphenhydramine, hydrocortisone, or a combination. In severe cases with rigors, meperidine is an option for premedication. Amphotericin B comes in different formulations and are not pharmaceutically equivalent. As a pharmacist, you should be aware of these different formulations: AmBisome is a liposomal formulation, Fungizone is the deoxycholate formulation and Abelcet is the lipid complex formulation. AmBisome and Abelcet have both shown to be less nephrotoxic than the conventional deoxycholate formulation (Fungizone).

AmBisome has very specific instructions regarding preparation and administration and is an important drug for pharmacists to be familiar with. AmBisome is only available in 50 mg vials and must be reconstituted using SWFI. If AmBisome is reconstituted using bacteriostatic water, sodium chloride, or other fluids containing benzyl alcohol or electrolytes, precipitation may occur, making Answer A a true statement.

It may then be further diluted in dextrose using a 5 micron filter (supplied with each vial) to prevent microparticulate-induced phlebitis. Each filter should only be used for one vial of drug. An in-line membrane filter may also be used during the infusion in addition to filtration during compounding as another preventative measure against phlebitis as long as the mean pore diameter of the in-line filter is not less than 1 micron. D5W is the most common diluent, but there are studies that show stability in D10W and D20W and can be used in pediatric patients who require fluid restriction. This makes answer B a true statement. The final product must then be protected from light. 

Answer C is a true statement because an IV line should always be flushed after administration of AmBisome. If it is being administered using a pre-existing IV line, it should also be flushed before the drug administration.

Answer D is a false statement and therefore incorrect because AmBisome has a lower rate of nephrotoxicity and infusion related events when compared to Fungizone, the deoxycholate formulation of amphotericin B.

Answer E is a true statement as while AmBisome can cause significant nephrotoxicity, it however does not require any dose adjustments in renal or hepatic insufficiency. In patients on traditional hemodialysis, it should be given after dialysis on those days.

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