Medical Pharmacology Chapter 37:  Antifungal Drugs

Antifungal Agents

• Amphotericin B: (Fungizone, Amphotec)

  • Routes of administration:

    • Colloidal preparation,  intravenous or intrathecal

  • Pharmacokinetics: amphotericin B

    • Very slow catabolism

    • Poor penetration into CNS/vitreous humor

    • Amphotericin B concentrations in pleural, peritoneal, articular exudates- adequate for many mycoses

• Clinical use:  amphotericin B

  • Most effective in treating:

    • Histoplasmosis

    • Blastomycosis

    • Paracoccidioidomycosis

    • Candidiasis

    • Cryptococcosis

  •  Less responsive:

    • Coccidiodomycosis

    • Extraarticular sporotricosis

    • Aspergillosis

    • Mucormycosis

  •  Very poor responding:

    • Chromoblastomycosis

    • Mycetoma

    • Pseudallescheriasis

•   Adverse Effects:  Amphotericin B (Fungizone, Amphotec)

  •  Febrile reactions (many poorly tolerated by patients with compromised cardiopulmonary function) -- recommend test dose

  •  Premedication with aspirin/acetaminophen or addition of hydrocortisone: reduces chills and fever associated with aphotericin B infusion

  •  Saline infusion: may reduce azotemia

  •  Permanent loss of renal function: dependent on total amphotericin B dose {usually noted in adult patients receiving > 3 grams}

  •  Anemia, hypokalemia, renal tubular acidosis, nausea, anorexia, weight loss, phlebitis, hypomagnesemia

  •  Intrathecal amphotericin B: considerable toxicity -- used in coccidioidal meningitis and refractory cryptococcal meningitis.

• Special Preparations:  amphotericin B:

  • Amphotericin B lipid complex (ABLC)

    • Reduced nephrotoxicity

    • Comparative efficacy unknown

•  Flucytosine (Ancobon)

  • Clinical Use:  Flucytosine

    • Cryptococcosis

    • Candidiasis

    • Chromoblastomycosis

• Mechanism of Action  flucytosine: converted to 5-fluorouracil (antimetabolite)

  • Used as single agent: drug resistance develops rapidly

  • Typically combined with amphotericin B

• Pharmacokinetics: flucytosine (Ancobon)

  • Well absorbed from the GI tract

  • Effective CNS penetration

  • Excreted unchanged by the kidney

  • Flucytosine blood levels very sensitive to kidney function

Sheppard,D. and Lampiris, H.W., Antifungal Agents, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 780-786

Bennett, J.E. Fungal Infections (Section 15: Infectious Diseases), In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., andBraunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1148-1163