      Document 0241
 DOCN  DRG0241
 UNIQUE IDENTIFIER        DRG-0006
 NAME OF SUBSTANCE        Amphotericin B [USAN 1995]
 REGISTRY NUMBER          1397-89-3
 STANDARD CHEMICAL NAME   33-((3-Amino-3,6-dideoxy-beta-D-mannopyranosy-
                          l)-oxy)-
                          1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trime-
                          thyl-13-oxo-14 ,39-di
                          oxabicyclo(33.3.1)nonatriaconta
                          -19,21,23,25,27,29,31-heptaene-36- carboxylic
                          acid [USAN 1995]
 SYNONYMS                 Amphozone [Merck Index 1989]
 SYNONYMS                 Fungizone [USAN 1995]
 SYNONYMS                 Fungilin [Merck Index 1989]
 SYNONYMS                 Ampho-Moronal [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 026
 PROTOCOL ID NUMBERS      NIAID ACTG 059
 PROTOCOL ID NUMBERS      FDA 001A
 PROTOCOL ID NUMBERS      FDA 012D
 PROTOCOL ID NUMBERS      FDA 012F
 PROTOCOL ID NUMBERS      FDA 012G
 PROTOCOL ID NUMBERS      FDA 012H
 PROTOCOL ID NUMBERS      FDA 012N
 PROTOCOL ID NUMBERS      FDA 051A
 PROTOCOL ID NUMBERS      NIAID ACTG 159
 PROTOCOL ID NUMBERS      NIAID ACTG 202
 PROTOCOL ID NUMBERS      FDA 131A
 PROTOCOL ID NUMBERS      FDA 051A
 PROTOCOL ID NUMBERS      NIAID ACTG 295
 PROTOCOL ID NUMBERS      FDA 254A
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: While the metabolic pathways
                          of this drug are unknown, its antifungal
                          action is probably due to binding to sterols
                          in the fungal cell membrane, changing
                          membrane permeability that allows loss of
                          potassium and small molecules from the cell.
                          Distributes to lungs, liver, spleen, kidneys,
                          adrenal glands, muscle, and other tissues at
                          potentially therapeutic concentrations, but
                          is usually undetectable in cerebrospinal
                          fluid. The drug circulating in plasma appears
                          to be highly bound (above 90 percent) to
                          plasma proteins and is poorly dialyzable.
                          Initial intravenous injection of 1-5 mg/day
                          gradually increased to 0.4-0.6 mg/kg/day
                          produced peak plasma levels ranging from
                          about 0.5 to 2 mcg/ml; after a rapid initial
                          fall, a plasma level plateau was attained at
                          about 0.5 mcg/ml; an elimination half-life of
                          about 15 days followed an initial plasma
                          half-life of about 24 hours.  Amphotericin B
                          is excreted slowly by the kidneys, with 2-5
                          percent of the dose excreted in its
                          biologically active form; cumulative urinary
                          output over 7 days amounts to about 40
                          percent of the amount of the drug infused.
                          [PDR 1995; USP DI 1995]
 DISEASES STUDIED/TREATED Acute cryptococcal meningitis [AmFAR Tx Dir
                          1995;7(4)]
 CLASSIFICATION CODE      Antifungal [USAN 1995]
 OTHER MAJOR USES         Used in treatment of patients with
                          progressive, potentially fatal fungal
                          infections, including: cryptococcosis
                          (torulosis); North American blastomycosis;
                          disseminated forms of moniliasis,
                          coccidioidomycosis, and histoplasmosis;
                          mucormycosis (phycomycosis) caused by species
                          of the genera Mucor, Rhizopus, Absidia,
                          Entomophthora, and Basidiobolus;
                          sporotrichosis; and aspergillosis [PDR 1991]
 SUBSTANCE INTERACTIONS   May interact with antineoplastic agents
                          (e.g., nitrogen mustard), corticosteroids and
                          corticotropin (ACTH), digitalis glycosides,
                          Flucytosine, other nephrotoxic medications,
                          skeletal muscle relaxants (e.g.,
                          Tubocurarine) and imidazoles (e.g.,
                          fluconazole). [PDR 1995]
 ADVERSE EFFECTS          May induce fever (often with shaking chills),
                          headache, anorexia, weight loss, nausea,
                          vomiting, diarrhea, muscle and joint pains,
                          reversible renal dysfunction, hypokalemia,
                          anemia, irregular heartbeat, blurred vision,
                          polyneuropathy, ear ringing, seizures,
                          troubled breathing, skin rash,
                          agranulocytosis, leukopenia, and
                          thrombocytopenia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity to amphotericin B. [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An antimycotic polyene
                          antibiotic [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C47H73NO17 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 924.1 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C61.09%;
                          H7.96%; N1.51%; O29.43% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: 0.1 mg/ml in water at pH2 or
                          pH11. Insoluble in water at pH 6-7. In
                          dimethylformamide (DMF) to 2-4 mg/ml. In
                          dimethylsulfoxide (DMSO) to 30-40 mg/ml
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Solids and solutions appear stable
                          for long periods between pH 4-10 when stored
                          at moderate temperatures out of contact with
                          light and air; decomposes gradually above 170
                          C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: UV max (methanol): 406,
                          382, 363, 345 nm [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Yellow to orange
                          lyophilized cake [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Dosage form is prepared by
                          addition of sodium desoxycholate to form a
                          colloidal dispersion. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: It is reconstituted by adding
                          sterile water for injection USP and diluting
                          with 5% dextrose injection USP and buffer.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: The infusion solution, after
                          reconstitution contains 0.1 mg Amphotericin B
                          per ml. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Slow intravenous infusion.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Prior to reconstitution, store at
                          2-8 C (36-46 F) in the dark; protect
                          solutions prepared for intravenous infusion
                          from light during administration. [USP DI
                          1995]
 MANUFACTURERS            Bristol-Myers Squibb Company
 MANUFACTURERS            Schering-Plough Corporation
 REFERENCES               Valero G, Graybill JR. Successful treatment
                          of cryptococcal meningitis with amphotericin
                          B colloidal dispersion: report of four cases.
                          Antimicrob Agents Chemother. 1995
                          Nov;39(11):2588-90.
 REFERENCES               Churchill D, Coker R. Amphotericin B as
                          primary therapy for cryptococcosis in
                          patients with AIDS: reliability of relatively
                          high doses over a relatively short period
                          [letter]. Clin Infect Dis 1995
                          Nov;21(5):1352-3.
 REFERENCES               Liu JS, Chang YY, Chen WH, Chen SS.
                          Amphotericin B-induced leukoencephalopathy in
                          a patient with cryptococcal meningitis. J
                          Formos Med Assoc 1995 Jul;94(7):432-4.
 REFERENCES               de Lalla F, Pellizzer G, Vaglia A, Manfrin V,
                          Franzetti M, Fabris P, Stecca C. Amphotericin
                          B as primary therapy for cryptococcosis in
                          patients with AIDS: reliability of relatively
                          high doses administered over a relatively
                          short period. Clin Infect Dis. 1995
                          Feb;20(2):263-6.
 REFERENCES               Leake HA, Appleyard MN, Hartley JP.
                          Successful treatment of resistant
                          cryptococcal meningitis with amphotericin B
                          lipid emulsion after nephrotoxicity with
                          conventional intravenous amphotericin B. J
                          Infect; VOL 28,ISS 3,1994,P319-22.
 REFERENCES               Chavanet PY, Garry I, Charlier N, Caillot D,
                          Kisterman JP, D'Athis M, Portier H. Trial of
                          glucose versus fat emulsion in preparation of
                          amphotericin for use in HIV infected patients
                          with candidiasis. BMJ. 1992 Oct
                          17;305(6859):921-5.
 REFERENCES               Moreau P, Milpied N, Fayette N, Ramee JF,
                          Harousseau JL. Reduced renal toxicity and
                          improved clinical tolerance of amphotericin B
                          mixed with intralipid compared with
                          conventional amphotericin B in neutropenic
                          patients. J Antimicrob Chemother 1992
                          Oct;30(4):535-41.
 REFERENCES               Buxton MJ, Dubois DJ, Turner RR, Sculpher MJ,
                          Robinson PA, Searcy C. Cost implications of
                          alternative treatments for AIDS patients with
                          cryptococcal meningitis. Comparison of
                          fluconazole and amphotericin B-based
                          therapies [see comments]. J Infect. 1991
                          Jul;23(1):17-31.
 REFERENCES               Larsen RA, Leal MA, Chan LS. Fluconazole
                          compared with amphotericin B plus flucytosine
                          for cryptococcal meningitis in AIDS. A
                          randomized trial [see comments]. Ann Intern
                          Med. 1990 Aug 1;113(3):183-7.
 REFERENCES               Panther LA, Sande MA. Cryptococcal meningitis
                          in the acquired immunodeficiency syndrome.
                          Semin Respir Infect. 1990 Jun;5(2):138-45.
 ENTRY MONTH              8906
 LAST REVISION DATE       960514
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
