      Document 0151
 DOCN  DRG0151
 UNIQUE IDENTIFIER        DRG-0096
 NAME OF SUBSTANCE        Amphotericin B Lipid Complex [USP DI 1995]
 REGISTRY NUMBER          1397-89-3
 STANDARD CHEMICAL NAME   Amphotericin B [USAN 1996]
 SYNONYMS                 ABLC [AmFAR Tx Dir 1995;7(4)]
 SYNONYMS                 Ambisome [Int Conf AIDS Jul 19-24;8(2):
                          (abstract no. PoB 3706)]
 SYNONYMS                 Abelcet [PR Newswire February 9, 1995]
 SYNONYMS                 Liposomal Amphotericin B [AmFAR Tx Dir Jan
                          1995;7(4)]
 PROTOCOL ID NUMBERS      FDA 051A
 PROTOCOL ID NUMBERS      NCI 92 C-47
 SECONDARY SOURCE ID      31916-12 [FDA 051A]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Amphotericin B is a polyene
                          antibiotic whose mechanism of action is
                          related to its capacity to bind to membrane
                          sterols, thereby forming transmembrane pores
                          that allow vital intracellular constituents
                          to leak out, eventually leading to cell
                          death. Amphotericin B therapy is associated
                          with side effects such as fever, chills,
                          hypotension, azotemia, hypokalemia and
                          normocytic anemia. In laboratory animals,
                          incorporation of amphotericin B in
                          phospholipid vesicles (liposomes) resulted in
                          a decreased number of toxic reactions and
                          enhanced therapeutic activity in a variety of
                          experimentally produced fungal infections.
                          The mechanisms of activity of liposomal
                          amphotericin B seem to be related to tissue
                          targeting, altered interactions between yeast
                          and mammalian cells, and possible
                          intracellular delivery to phagocytic cells.
                          In rodents and humans, liposomes are taken up
                          preferentially by the liver, spleen, lung,
                          kidneys and bone marrow -- organs that target
                          for fungal infections. When incubated in
                          vitro with yeast cells, liposomal
                          amphotericin B retains the antifungal potency
                          of amphotericin B but is not toxic to red
                          blood cells. Liposomes are avidly taken up by
                          circulating and tissue phagocytes, suggesting
                          the possibility of a second carrier and a
                          reservoir for the drug. Other mechanisms such
                          as immunostimulation and capillary leakage
                          caused by fungal endothelial invasion may
                          also play a role. [Arch Intern Med, 1989
                          November; 148]
 DISEASES STUDIED/TREATED Disseminated fungal infections including
                          cryptococcal meningitis, systemic
                          candidiasis, coccidioidomycosis, and
                          aspergillosis [AmFAR Tx Dir 1995;7(4)]
 DISEASES STUDIED/TREATED FDA approved 11/20/95 for patients with
                          aspergillosis who are refractory to or
                          intolerant of conventional amphotericin B
                          [FDA Bulletin]
 CLASSIFICATION CODE      Antifungal [AmFAR Tx Dir 1995;7(4)]
 SUBSTANCE INTERACTIONS   Interacts with corticosteroids, salicylates
                          or other drugs known to interfere with
                          prostaglandin synthesis, interferon,
                          interleukin-2, and isoprinosine. [FDA 051A]
 ADVERSE EFFECTS          ABLC has been associated with transient
                          increases in transaminases, transient renal
                          toxicity, fever, and chills. [AmFAR Tx Dir
                          1995;7(4)]
 CONTRAINDICATIONS        Contraindicated with a history of
                          hypersensitivity/anaphylactoid reaction
                          attributed to amphotericin B; pregnancy;
                          breastfeeding. [FDA 051A]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A molecule containing two
                          lipids (DMPC/DMPG) and amphotericin B [AmFAR
                          Tx Dir 1993;6(3)] [AmFAR Tx Dir Dec 1990]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Liposome encapsulation
                          delivers the drug in a vehicle that tends to
                          be taken up by organs rich in
                          reticuloendothelial cells, the site of most
                          disseminated fungal infections [AmFAR Tx Dir
                          Dec 1990] [AmFAR Tx Dir 1993;6(3)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C47H73NO17 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 924.11 (Amphotericin B)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C61.09%, H7.96%,
                          N1.51%, O29.43% (Amphotericin B) [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Polyene antibiotic
                          (Amphotericin B) [Merck Index 1989]
 MANUFACTURERS            Liposome Company Inc
 MANUFACTURERS            Fujisawa USA Inc
 REFERENCES               Torre-Cisneros J, Villanueva JL. Efficacy of
                          liposomal amphotericin B in the treatment of
                          visceral leishmaniasis in patients coinfected
                          with the human immunodeficiency virus
                          [letter]. Clin Infect Dis. 1995
                          Jan;20(1):191.
 REFERENCES               Davidson RN, Di Martino L, Gradoni L,
                          Giacchino R, Russo R, Gaeta GB, Pempinello R,
                          Scott S, Raimondi F, Cascio A, et al.
                          Liposomal amphotericin B (AmBisome) in
                          Mediterranean visceral leishmaniasis: a
                          multi-centre trial. Q J Med. 1994
                          Feb;87(2):75-81.
 REFERENCES               Viviani MA, Rizzardini G, Tortorano AM, Fasan
                          M, Capetti A, Roverselli AM, Gringeri A,
                          Suter F. Lipid-based amphotericin B in the
                          treatment of cryptococcosis. Infection. 1994
                          Mar-Apr;22(2):137-42.
 REFERENCES               Coker RJ, Viviani M, Gazzard BG, Du Pont B,
                          Pohle HD, Murphy SM, Atouguia J, Champalimaud
                          JL, Harris JR. Treatment of cryptococcosis
                          with liposomal amphotericin B (AmBisome) in
                          23 patients with AIDS. AIDS. 1993
                          Jun;7(6):829-35.
 REFERENCES               Torre-Cisneros J, Villanueva JL, Kindelan JM,
                          Jurado R, Sanchez-Guijo P. Successful
                          treatment of antimony-resistant visceral
                          leishmaniasis with liposomal amphotericin B
                          in patients infected with human
                          immunodeficiency virus [see comments]. Clin
                          Infect Dis. 1993 Oct;17(4):625-7.
 REFERENCES               al-Haddadin D, Fan-Havard P, Boghossian J,
                          Marton R, Vincent-Graber D, Dungo L, Eng RH,
                          Johnson ES. Amphotericin B-lipid complex
                          (ABLC) in treatment of cryptococcal
                          meningitis in AIDS. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B109 (abstract no. PoB 3132).
 REFERENCES               Lazanas M, Tsekes G, Papandreou S, Harhalakis
                          N, Nikiphorakis E, Saroglou G. Liposomal
                          amphotericin B for leishmaniasis treatment of
                          AIDS patients unresponsive to antimonium
                          compounds. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B143 (abstract no. PoB 3341).
 REFERENCES               Coker R, Viviani M, Gazzard BG, Du Pont B,
                          Murphy SM, Pohle HD, Harris JR. AmBisome
                          (liposomal amphotericin B) for disseminated
                          cryptococcosis. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B113 (abstract no. PoB 3156).
 REFERENCES               Lazar JT, Ksionski GE. Efficacy and safety of
                          amBisome (liposomal amphotericin B) in
                          primary episodes of cryptococcosis in
                          patients with HIV infection. Int Conf AIDS.
                          1991 Jun 16-21;7(2):226 (abstract no.
                          W.B.2177).
 REFERENCES               Coker RJ. Murphy SM, Harris JR. Experience
                          with liposomal amphotericin B (AmBisome) in
                          cryptococcal meningitis in AIDS. J Antimicrob
                          Chemother. 1991 Oct;28 Suppl B:105-9.
 ENTRY MONTH              9011
 LAST REVISION DATE       951130
 

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