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Antimicrobials

Liposomal Amphotericin B (AmBisome®)

Guidelines for use

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1. Spectrum of activity

Active against:

  • Candida species: C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei
  • Aspergillus species
  • Cryptococcus species
  • Dimorphic Fungi (Histoplasma, Coccidiodes, Blastomyces)
  • Zygomycetes
  • Sporothrix

Not active against:

  • Candida lusitaniae

2. Clinical use (consult Infectious Diseases)

  • Empiric treatment of invasive candidiasis in critically-ill or neutropenic patients (typically second-line to less toxic agents)
  • Treatment of disseminated histoplasmosis, coccidioidomycosis and blastomycosis
  • Treatment of aspergillus infections (typically second-line to voriconazole)
  • Treatment of cryptococcosis
  • Treatment of mucormycosis

3. Precautions

  • Administration of amphotericin B may be complicated by infusion-mediated reactions (see Guidelines for management of toxicities)
  • Administration of amphotericin B is commonly complicated by nephrotoxicity (see Guidelines for management of toxicities)
  • Pregnancy and breastfeeding - for safety information, see Table on Safety of Anti-infective therapy in Pregnancy & Lactation

4. Adverse Effects

  • Infusion-mediated reactions: fever, chills, rigors, headache, nausea and vomiting (lower risk with liposomal amphotericin B)
  • Nephrotoxicity (lower risk with liposomal amphotericin B)
    • typically reversible upon discontinuation; increased risk of permanent toxicity with amphotericin B deoxycholate with cumulative doses > 5 g)
  • Electrolyte abnormalities (hypokalemia, hypomagnesemia)
  • Phlebitis
  • Transamintitis
  • Normochromic, normocytic anemia

5. Dosage

Liposomal Amphotericin B

  • Usual Dosage: 3-6 mg/kg/day (occasionally doses of 10-15 mg/kg/day may be required)

Renal Insufficiency: no dose adjustment in renal impairment; consider use of liposomal amphotericin B

6. Monitoring

  • Baseline and periodic serum creatinine, transaminases, electrolytes (sodium, potassium, magnesium) and CBC

7. Management of Toxicities

*Also see IV drug monograph on pharmacy intranet page

  • Nephrotoxicity: ensure adequate hydration throughout therapy; pre-dose sodium loading may reduce the risk of nephrotoxicity
    • Infuse 500 mL of normal saline over 30 minutes before and after each daily dose to reduce the risk of nephrotoxicity
    • Consider prolonging the infusion time
  • Infusion-related reactions (fever, chills, rigors):
    • Temporarily interrupt the infusion - if not resolved in 15 minutes, consider the administration of meperidine 50 mg IV diluted in 10mL NS over 5 minutes (flush with D5W before and after)
    • Hydrocortisone sodium succinate (Solu-Cortef®) 25-50 mg may be added to the infusion solution
    • Consider pre-mediation with meperidine or ibuprofen
  • Phlebitis (peripheral veins):
    • Attempt to rotate IV sites regularly to minimize risk of phlebitis
    • Heparin may be added in a dose of 1 unit per mL of amphotericin B solution
    • Infusion via central venous catheter should be considered in patients not tolerating peripheral administration and particularly for infusion of more concentrated solutions (>0.1 mg/mL)

Last updated: November 18, 2019