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Amphotericin B

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

  • See also
  1. Antifungal Medication
  2. Topical Antifungal
  • Indications
  1. Preferred agent for deep Fungal Infections in pregnancy (long safety data record)
  2. Covers most medically important fungi, but with serious adverse effects (esp. nephrotoxicity)
  3. 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)
  • Containdications
  1. Resistant organisms
    1. Fusarium (variable Amphotericin B activity)
    2. Aspergillus terreus
    3. Scedosporium apiosermum
    4. Scedosporium prolificans
    5. Trichosporon
    6. Candida lusitaniae
  • 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
  • Medications
  1. Amphotericin B Deoxycholate (Fungizone)
    1. Conventional, older, generic, inexpensive formulation with greatest nephrotoxicity and reaction risk
    2. Has been compounded by some inpatient pharmacies in Intralipid to reduce reactions
      1. Amphotericin B Deoxycholate 1-2 mg per 1 ml Intralipid
  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)
  • 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. Amphotericin combined with the phospholipids DMPG and DMPC
    2. Associated with less nephrotoxicity
    3. Dose 5 mg/kg/day IV infused at 2.5 mg/kg/hour
    4. Shake infusion bag every 2 hours
  4. Liposomal Amphotericin B (L-AmB, Ambisome)
    1. Unilamellar liposome mix of Amphotericin B surrounded by various lipids (DMPG, lecithin, Cholesterol)
    2. Associated with less nephrotoxicity and infusion reactions
    3. Dose 3 to 5 mg/kg/day IV infused over 2 hours
  5. Amphotericin B Cholesteryl Sulfate Complex or Colloidal Dispersion (ABCD, Amphotec)
    1. Amphotericin combined with Cholesterol sulfate
    2. Associated with less nephrotoxicity
    3. Dose 3 to 4 mg/kg/day IV
  • Pharmacokinetics
  1. Narrow therapeutic window
  2. Poor oral Bioavailability
  3. Used primarily IV (also used intrathecally and as a Bladder wash)
  • 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. Nephrotoxicity is typically reversible on stopping Amphotericin B
    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)
    4. Monitor Renal Function closely (see below)
  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. Phlebitis or Thrombophlebitis at infusion site
    2. Anemia
    3. Renal Tubular Acidosis (increased bicarbonate excretion)
    4. Hypokalemia and Hypomagnesemia (secondary to Renal Tubular Acidosis)
    5. Weight loss
    6. Malaise
    7. Leukopenia (mild)
    8. Cardiotoxicity (rare)
    9. Liver toxicity (rare, but may occur with lipid formulations)
    10. 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
  • Safety
  1. Unknown safety in Lactation
  2. Pregnancy Category B
    1. Preferred agent for deep Fungal Infections in pregnancy (long safety data record)
  • Monitoring
  1. Complete Blood Count
  2. Urinalysis
  3. Comprehensive metabolic panel (including liver function and Renal Function)
  • Efficacy
  1. Lipid formulations have similar efficacy to Amphotericin B Deoxycholate
  • Resources
  1. Amphotericin B lyophilized powder
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0a54943-9ce4-4f3e-b681-a1a9144c16ce
  • References
  1. (2012) Med Lett Drugs Ther 10(120): 61-8