      Document 0170
 DOCN  DRG0170
 UNIQUE IDENTIFIER        DRG-0077
 NAME OF SUBSTANCE        Fiacitabine [USAN 1996]
 REGISTRY NUMBER          69123-90-6
 RELATED REGISTRY NUMBER  69124-05-6
 STANDARD CHEMICAL NAME   2(1H)-Pyrimidinone, 4-amino-1-
                          (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5--
                          iodo- [USAN 1996]
 SYNONYMS                 FIAC [USAN 1996]
 SYNONYMS                 1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl-
                          )-5-iodocytosine [USAN 1993]
 SYNONYMS                 2'-Fluoro-5-iodo-1-beta-D-arabinofuranosylcyt-
                          osine [CHEMLINE]
 SYNONYMS                 2'-Fluoro-5-iodo-aracytosine [MeSH]
 SYNONYMS                 1-(2-Fluoro-2-deoxy-beta-D-arabinofuranosyl)--
                          5-iodocytosine [MeSH]
 SYNONYMS                 1-(2-Deoxy-2-fluoro-beta-arabinofuranosyl)-5--
                          iodocytosine [MeSH]
 SYNONYMS                 2(1H)-Pyrimidinone,4-amino-1-(2-deoxy-2-fluor-
                          o-beta-D-arabinofuranosyl)-5-iodo [MeSH]
 PROTOCOL ID NUMBERS      NIAID ACTG 122 FIAC
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: FIAC is rapidly and virtually
                          completely absorbed after a single oral dose,
                          and principally converted into its primary
                          deaminated uracil metabolite (fialuridine,
                          FIAU), which is then eliminated by renal
                          excretion and further biotransformation via
                          deiodinization and glucuronic conjugation.
                          While the specific mechanism of action of
                          FIAC is unknown, it appears to exert its
                          effect on cytomegalovirus by serving as
                          substrate for viral DNA polymerase. Both FIAC
                          and FIAU demonstrate potent and nearly
                          identical in vitro activities against HSV-1,
                          HSV-2, VZV, CMU, and HBV. Following
                          intravenous injection of 50 or 100 mg/sq
                          meter (about 1.2 or 2.5 mg/kg, respectively),
                          the plasma half-lives of FIAC and FIAU were
                          1.36 and 3.91 hours, respectively.  Peak
                          plasma levels of FIAC and FIAU were observed
                          1-2 hours after oral dosing, and plasma
                          levels of FIAU were equal or greater than the
                          cytomegalovirus in vitro ED-50 at 8 hours in
                          all 3 patients given 50 or 100 mg/sq meter
                          (about 1.2 or 2.5 mg/kg, respectively);
                          8-hour plasma levels in these patients (after
                          oral administration) averaged more than twice
                          those observed after intravenous injection of
                          FIAC (hence, daily oral doses of as little as
                          100 mg/sq meter (about 2.5 mg/kg given at
                          8-hour intervals might be expected to provide
                          plasma levels of FIAC and FIAU that
                          continuously exceed the in vitro minimum
                          inhibitory levels for cytomegalovirus).
                          Investigators report that toxicities seen
                          with FIAC may be due to metabolism. [Int Conf
                          AIDS 1991 Jun 16-21;7(2): (abstract no. W.B.
                          2290)] [NIAID ACTG 122] [AmFAR Tx Dir
                          1993;6(3)]
 DISEASES STUDIED/TREATED Treatment of cytomegalovirus infections
                          [AmFAR Tx Dir 1993;6(3)] [NIAID ACTG 122]
 DISEASES STUDIED/TREATED Phase I studies of FIAC have been
                          discontinued due to gastrointestinal toxicity
                          and severe fatigue [AmFAR Tx Dir 1993;6(3)]
 CLASSIFICATION CODE      Antiviral [USAN 1996]
 ADVERSE EFFECTS          Phase I studies of FIAC have been
                          discontinued  due to gastrointestinal
                          toxicity, bone marrow suppression, and severe
                          fatigue. May cause mild to moderate nausea,
                          hematologic toxicity, thrombocytopenia,
                          irregular pancytopenia, alteration of
                          leukocyte and platelet levels, elevation of
                          SGOT, gastrointestinal intolerance,
                          reversible central nervous system symptoms
                          (confusion, myoclonic jerking, and seizures),
                          and possible hypotension with increased
                          pulmonary edema. [AmFAR Tx Dir 1993;6(3)]
                          [NIAID ACTG 122]
 CONTRAINDICATIONS        Should not be used in patients exhibiting HIV
                          wasting syndrome, presenting clinical or
                          x-ray evidence of bronchitis, pneumonitis,
                          pulmonary edema, effusion, or suspected
                          active tuberculosis, or having any unstable
                          medical condition (including serious
                          cardiovascular, infections, oncologic, renal,
                          or hepatic conditions), or any
                          cytomegalovirus end organ disease. [NIAID
                          ACTG 122]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Fluorinated pyrimidine
                          nucleoside analog [Transplant Proc 1991
                          Jun;23(3 Supp 3)] [NIAID ACTG 122]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C9H11FIN3O4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water [NIAID ACTG 122]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Crystalline powder
                          [NIAID ACTG 122]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 371.11 [USAN 1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM:  Powder dissolved in USP
                          purified water (4 mg/ml). [NIAID ACTG 122]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY:  Oral. [AmFAR Tx Dir
                          1993;6(3)]
 SUBSTANCE DELIVERY DATA  STORAGE:  Store powder between 15-30 degrees
                          C (59-86 degrees F); store reconstituted
                          aqueous solution under refrigeration (36-46
                          degrees F). [NIAID ACTG 122]
 MANUFACTURERS            Oclassen Pharmaceuticals
 REFERENCES               Pottage JC, Kessler HA, Kapell K, Benson CA.
                          Acyclovir resistant (ACV-R) herpes simplex:
                          susceptibility to alternative antiviral
                          agents. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B126 (abstract no. PoB 3238).
 REFERENCES               Tartaglione T, Hooton TM, Jones T, Smiles K,
                          Corey L. ACTG 122: phase II tolerance study
                          of oral FIAU in HIV-infected persons. Int
                          Conf AIDS. 1991 Jun 16-21;7(2):254 (abstract
                          no. W.B. 2290).
 REFERENCES               King DH. Fluorinated pyrimidines: a new
                          change for old drugs. Transplant Proc. 1991
                          Jun;23(3 Suppl 3):168-70
 REFERENCES               Resta S, Wolitz R, Merigan TC. CMV RETINITIS
                          IN THE AIDS PATIENT. AIDS Updates; 3(3):1-12
                          1990.
 ENTRY MONTH              9001
 LAST REVISION DATE       951031
 

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