Amphotericin B

Aka: Amphotericin B, Amphotericin B Lipid Complex, Liposomal Amphotericin B, Amphotericin B Cholesteryl Sulfate Complex, Fungizone, Abelcet, Ambisome, Amphotec

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II. Indications

  1. Preferred agent for deep fungal infections in pregnancy (long safety data record)
  2. Systemic, invasive, life-threatening fungal infections (including Meningitis, cystitis) and some Protozoa infections
    1. Largely replaced by newer, less toxic fungicides
    2. Candidemia
    3. Symptomatic candida cystitis or Pyelonephritis
    4. Cryptococcal Meningitis (HIV Infection, administered with Flucytosine)

III. Containdications

  1. Resistant organisms
    1. Fusarium (variable Amphotericin B activity)
    2. Aspergillus terreus
    3. Scedosporium apiosermum
    4. Scedosporium prolificans
    5. Trichosporon
    6. Candida lusitaniae

IV. Mechanism

  1. Polyene, macrolide Antifungal
    1. Produced by Streptomyces nodosus (soil Bacteria from Orinoco river region of Venezuela)
  2. Amphotericin B binds to ergosterol within the fungal cell membrane
    1. Results in fungal cell Membrane Depolarization and increased permeability
    2. Fungal cell leaks key intracellular components, and ruptures

V. Medications

  1. Amphotericin B Deoxycholate (Fungizone)
    1. Conventional, older, generic, inexpensive formulation with greatest Nephrotoxicity Risk
  2. Amphotericin B Lipid Formulations
    1. Amphotericin B Lipid Complex (ABLC, Abelcet)
    2. Liposomal Amphotericin B (L-AmB, Ambisome)
    3. Amphotericin B Cholesteryl Sulfate Complex (ABCD, Amphotec)

VI. Dosing: Adult

  1. Background
    1. Dosing and duration of Amphotericin B depends on infection source and organism type
  2. Amphotericin B Deoxycholate
    1. Dosing has also been used off-label in children
    2. Test dose
      1. Give 0.1 mg/kg (up to 1 mg) in 20 ml D5W IV over 20 to 30 minutes
      2. May continue with standard dosing if tolerated at 2 to 4 hours after test dose
    3. Start: 0.25 mg/IV over 2 to 6 hours daily
    4. Advance to 0.7 to 1.0 mg/kg (up to 1.5 mg/kg) IV over 2 to 6 hours daily
      1. Dosing depends on type of fungal organism (see other references)
    5. Administer with 10 to 15 ml/kg (up to 1 Liter) Normal Saline
  3. Amphotericin B Lipid Complex (ABLC, Abelcet)
    1. Dose 5 mg/kg/day IV infused at 2.5 mg/kg/hour
    2. Shake infusion bag every 2 hours
  4. Liposomal Amphotericin B (L-AmB, Ambisome)
    1. Dose 3 to 5 mg/kg/day IV infused over 2 hours
  5. Amphotericin B Cholesteryl Sulfate Complex (ABCD, Amphotec)
    1. Dose 3 to 4 mg/kg/day IV

VII. Pharmacokinetics

  1. Narrow therapeutic window

VIII. Adverse Effects

  1. Background
    1. Greatest adverse effects are with the original, non-lipid formulation
    2. Amphotericin B carries the nickname "Ampho-Terrible"
  2. Nephrotoxin
    1. Nephrotoxicity most significant with Amphotericin B Deoxycholate (non-lipid formulation)
      1. Decreased nephrotoxicity with liposome encased amphotericin (Abelcet, Abisome)
    2. Reduced risk with 1 Liter of Normal Saline load before or during infusion (if not contraindicated)
    3. Avoid with other Nephrotoxins (e.g. Aminoglycosides, Cyclosporine, Tacrolimus)
  3. Intravenous infusion reaction
    1. Background
      1. Onset 1 to 3 hours from start of infusion, and lasting 1 hour
      2. Decreased symptoms with subsequent infusions
      3. Consider pretreatment with Acetaminophen, NSAIDs or Diphenhydramine
      4. Reaction severity varies with formulation (listed most to least)
        1. Amphotericin B Deoxycholate (most severe)
        2. Amphotericin B Cholesteryl Sulfate Complex (ABCD, Amphotec)
        3. Amphotericin B Lipid Complex (ABLC, Abelcet)
        4. Liposomal Amphotericin B (L-AmB, Ambisome, least severe)
    2. Fever and chills
    3. Nausea
    4. Headache
    5. Tachypnea
    6. Hypotension
  4. Other adverse effects
    1. Thrombophlebitis
    2. Anemia
    3. Hypokalemia and Hypomagnesemia (secondary to Renal Tubular Acidosis)
    4. Weight loss
    5. Malaise
    6. Leukopenia (mild)
    7. Cardiotoxicity (rare)
    8. Liver toxicity (rare, but may occur with lipid formulations)
    9. Acute severe truncal pain (Chest Pain, Abdominal Pain, back pain)
      1. Limited to Liposomal Amphotericin B (L-AmB, Ambisome) and of unclear cause
      2. Slow infusion and pretreat with Diphenhydramine

IX. Safety

  1. Pregnancy Category B
  2. Unknown safety in Lactation

X. Monitoring

  1. Complete Blood Count
  2. Urinalysis
  3. Comprehensive metabolic panel (including liver function and Renal Function)

XI. Efficacy

  1. Lipid formulations have similar efficacy to Amphotericin B Deoxycholate

XII. Resources

  1. Amphotericin B lyophilized powder
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0a54943-9ce4-4f3e-b681-a1a9144c16ce

XIII. References

  1. (2012) Med Lett Drugs Ther 10(120): 61-8

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