      Document 0198
 DOCN  DRG0198
 UNIQUE IDENTIFIER        DRG-0049
 NAME OF SUBSTANCE        Flucytosine [USAN 1996]
 REGISTRY NUMBER          2022-85-7
 STANDARD CHEMICAL NAME   5-Fluorocytosine [USAN 1996]
 SYNONYMS                 Ancobon (Hoffman-La Roche) [USAN 1996]
 SYNONYMS                 4-Amino-5-fluoro-2(1H)-pyrimidinone [Merck
                          Index 1989]
 SYNONYMS                 2-Hydroxy-4-amino-5-fluoropyrimidine [Merck
                          Index 1983]
 SYNONYMS                 Alcobon [Merck Index 1989]
 SYNONYMS                 Ancotil [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 059
 PROTOCOL ID NUMBERS      FDA 012F
 PROTOCOL ID NUMBERS      FDA 012G
 PROTOCOL ID NUMBERS      FDA 213A
 PROTOCOL ID NUMBERS      NIAID ACTG 159
 PROTOCOL ID NUMBERS      NIAID ACTG 202
 SECONDARY SOURCE ID      5-FC [Merck Index 1989]
 SECONDARY SOURCE ID      Ro 2-9915 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Flucytosine has in vitro and
                          in vivo activity against Candida and
                          Cryptococcus. It has been proposed it acts
                          directly on fungal organism by competitive
                          inhibition of purine and pyrimidine uptake
                          and indirectly by intracellular metabolism to
                          5-fluorouracil. Flucytosine enters the cell
                          via cytosine permease; and is metabolized to
                          5-fluorouracil within fungal organisms. The
                          5-fluorouracil is extensively incorporated
                          into fungal RNA and inhibits synthesis of
                          both DNA and RNA. The result is unbalanced
                          growth and death of the fungal organism.
                          Flucytosine is rapidly and well absorbed from
                          the gastrointestinal tract but is not
                          significantly metabolized and exhibits very
                          low protein binding. It is widely distributed
                          throughout the body, but its exact
                          distribution in body fluids and organs is not
                          known (cerebrospinal fluid levels may range
                          from 60-90 percent of those in the serum).
                          Its half-life in normal and impaired renal
                          function is 0.5-2 and 4-6 hours,
                          respectively, its time to peak serum
                          concentration is 4-6 hours, and its
                          elimination is largely renal, with about
                          80-90 percent excreted as the unchanged drug.
                          [PDR 1995; USP DI 1995]
 DISEASES STUDIED/TREATED Used with amphotericin B for treating acute
                          cryptococcal meningitis [AHFS Drug
                          Information 1995]
 CLASSIFICATION CODE      Antifungal [USAN 1996]
 OTHER MAJOR USES         Flucytosine is indicated only in the
                          treatment of serious infections caused by
                          susceptible strains of Candida and/or
                          Cryptococcus [PDR 1995]
 SUBSTANCE INTERACTIONS   Interacts with parenteral amphotericin B,
                          blood dyscrasia-causing medications, other
                          bone marrow depressants, and with radiation
                          therapy. Cytarabine may be a competitive
                          inhibitor of flucytosine. [USP DI 1995]
 ADVERSE EFFECTS          Adverse reactions include cardiac arrest,
                          chest pain, dyspnea, respiratory arrest,
                          rash, pruritus, urticaria, photosensitivity,
                          nausea, emesis, abdominal pain, diarrhea,
                          anorexia, dry mouth, duodenal ulcer,
                          gastrointestinal hemorrhage, hepatic
                          dysfunction, jaundice, ulcerative colitis,
                          bilirubin elevation, azotemia, creatinine,
                          BUN elevation, crystalluria, renal failure,
                          anemia, agranulocytosis, eosinophilia,
                          leukopenia, pancytopenia, and
                          thrombocytopenia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          hypersensitivity to the drug. Should be
                          considered with extreme caution for patients
                          with impaired renal function and patients
                          with bone marrow depression. Since the drug
                          has shown experimental teratogenic effects,
                          its potential benefits and hazards should be
                          considered before administering to pregnant
                          or lactating women or women of child-bearing
                          age. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Fluorinated pyrimidine
                          chemically related to fluorouracil and
                          floxuridine [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C4H4FN3O [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 129.09 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C37.21%; H3.12%;
                          F14.72%; N32.55%; O12.39% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 295-297 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: 1.5 g/ml (25 C, in water) [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white
                          crystalline powder which may be odorless or
                          have a slight odor [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 250 mg and 500 mg gelatin
                          capsules. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room temperature
                          of 15-30 C (59-86 F) in a tight,
                          light-resistant container. [USP DI 1995]
 MANUFACTURERS            Hoffmann-La Roche Laboratories
 REFERENCES               Larsen RA, Bozzette SA, Jones BE, Haghighat
                          D, Leal MA, Forthal D, Bauer M, Tilles JG,
                          McCutchan JA, Leedom JM. Fluconazole combined
                          with flucytosine for treatment of
                          cryptococcal meningitis in patients with
                          AIDS. Clin Infect Dis. 1994 Oct;19(4):741-55.
 REFERENCES               Milefchik E, Leal M, Haubrich R, See D,
                          Bozzette S, Larsen R. High dose fluconazole
                          with and without flucytosine for AIDS
                          associated cryptococcal meningitis. Int Conf
                          AIDS. 1993 Jun 6-11;9(1):55 (abstract no.
                          WS-B12-5).
 REFERENCES               Archidiacono MI, Cantaluppi P. Itraconazole
                          in pulmonary aspergillosis. Int Conf AIDS.
                          1993 Jun 6-11;9(1):367 (abstract no.
                          PO-B09-1388).
 REFERENCES               Powderly WG. Therapy for cryptococcal
                          meningitis in patients with AIDS. Clin Infect
                          Dis. 1992 Mar;14 Suppl 1:S54-9.
 REFERENCES               de Gans J, Portegies P, Tiessens G, Eeftinck
                          Schattenkerk JK, van Boxtel CJ, van Ketel RJ,
                          Stam J. Itraconazole compared with
                          amphotericin B plus flucytosine in AIDS
                          patients with cryptococcal meningitis. AIDS.
                          1992 Feb;6(2):185-90.
 REFERENCES               Gazapo Carretero E, Garcia Aguado C, Adrados
                          de Llano M, Martinez Blanco ML, Verdejo Ortes
                          J, Gonzalez Lahoz JM. [Cryptococcosis in AIDS
                          patients: a study of 19 cases]. Rev Clin Esp.
                          1992 May;190(9):450-4.
 REFERENCES               Jones B, Larsen RA, Forthal D, Haghighat D,
                          Bozzette S. Treatment of  non-meningeal
                          cryptococcal disease in HIV-infected persons.
                          Abstr Annu Meet Am Soc Microbiol. 1991 May
                          5-9;91:409 (abstract no. F-4).
 REFERENCES               Jones BE, Larsen RA, Bozzette S, Haghighat D,
                          Leedom JM, McCutchan JA. A phase II trial of
                          fluconazole plus flucytosine for cryptococcal
                          meningitis. Int Conf AIDS. 1991 Jun
                          1-21;7(2):266 (abstract no. W.B.2337).
 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 Inter
                          Med. 1990 Aug 1;113(3):183-7.
 ENTRY MONTH              8906
 LAST REVISION DATE       951109
 

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