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Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

Liposomal AMPHOTERICIN B

 

Indication

  • the treatment of severe systemic infections caused by susceptible fungal pathogens, including Candida species, in patients who are refractory to, or intolerant of, conventional amphotericin B

Clinical Pharmacology

  • the active component of liposomal amphotericin B is amphotericin B which acts by binding to sterols in the fungal cell membrane
  • the pharmacokinetics of liposomal amphotericin B are different from those of conventional amphotericin B
  • liposomal amphotericin B (5 mg/kg/day) produces serum levels that are comparable to 1/10 the dose of conventional amphotericin B (0.6 mg/kg/day) ; this can be explained by a much larger volume of distribution for liposomal amphotericin B - the drug accumulates in tissues at very high concentrations(1)

    OrganAmphotericin B Tissue Concentration (mcg/g)
    Spleen
    Lung
    Liver
    Lymph Node
    Kidney
    Heart
    Brain
    290
    222
    196
    7.6
    6.9
    5
    1.6

Side Effects

Monitor for:

  • hypomagnesemia, hyper/hypo-kalemia and hypocalcemia
  • liver function test abnormalities
  • increased BUN, serum creatinine

Dose

  • 3-5 mg / kg / day
  • administer by slow infusion over 2 hours (2.5 mg / kg / h)
  • there are no firm guidelines for dose adjustment in renal impairment; the patient's overall clinical condition should be considered
  • no dosage adjustment is required for patients with hepatic impairment

Clearing Residual Ambisome® from IV Line

After Ambisome® has infused a light yellow tinge remains in the IV line. This likely represents an extremely small amount of the total dose. The following method is suggested to deal with this issue.

  1. After the infusion is complete (at 2 hours) flush with 2 mL of a dextrose solution (beginning proximal to the point where the yellow tinge appears).
  2. If there is a yellow tinge to the tubing, disconnect the tubing from the baby and the pump, and let the IV run freely for about 5 seconds to clear the tubing.
  3. If there is noticeable clumping at any time during the above procedures please contact Pharmacy.

Stability with other drugs

  • do not mix with other drugs or electrolytes

Supplied

  • 2 mg/mL syringe, prepared by the Department of Pharmacy, using 5% dextrose/water as a diluent
  • 50 mg vial is commercially available, but product needs to be further diluted to 2 mg/mL before use
  • store at 2 to 6oC, protect from light

References

  1. Ambisome monograph in the e-CPS accesed online at https://www.e-therapeutics.ca/cps.showMonograph.action?simpleMonographId=m023300, on June 3, 2011.
  2. Linder N, Klinger G, Shalit I, et al. Treatment of candidaemia in premature infants: comparison of three amphotericin B preparations. Journal of Antimicrobial Chemotherapy 2003:52: 663-7.
  3. Jeon GW, Koo SH, Lee JH, et al. A Comparison of Ambisome to Amphotericin B for Treatment of Systemic Candidiasis in Very Low Birth Weight Infants. Yonsei Medical Journal 2007; 48(4): 619-627.
  4. Turkova A, Roilides E and Sharland M. Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy-is there a ‘right’ choice? Curr Opin Infect Dis 2011: 24: 163-171.



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