      Document 0127
 DOCN  DRG0127
 UNIQUE IDENTIFIER        DRG-0120
 NAME OF SUBSTANCE        Trifluridine (Ophthalmic) [USAN 1996]
 REGISTRY NUMBER          70-00-8
 STANDARD CHEMICAL NAME   2'-Deoxy-5-(trifluoromethyl)uridine [PDR
                          1995]
 SYNONYMS                 5-(Trifluoromethyl)-2'-deoxyuridine [Merck
                          Index 1989]
 SYNONYMS                 Viroptic [PDR 1995]
 SYNONYMS                 Trifluorothymidine [PDR 1995]
 SYNONYMS                 Virophta [Merck Index 1989]
 SYNONYMS                 Thymidine,alpha,alpha,alpha-trifluoro- [USAN
                          1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 172
 SECONDARY SOURCE ID      F3TDR [Merck Index 1989]
 SECONDARY SOURCE ID      TFT Thilo [Merck Index 1989]
 SECONDARY SOURCE ID      TFT [AmFAR Tx Dir 1995;7(4)]
 SECONDARY SOURCE ID      F3TdR [PDR 1995]
 SECONDARY SOURCE ID      F3T [PDR 1995]
 SECONDARY SOURCE ID      NSC 75,5200 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION:  Exact mechanism of antiviral
                          activity has not been fully elucidated but
                          appears to involve inhibition of viral
                          replication.  Trifluridine, instead of
                          thymidine, is incorporated into viral DNA
                          during replication, which results in the
                          formation of defective proteins and an
                          increased mutation rate.  Trifluridine also
                          reversibly inhibits thymidylate synthetase,
                          an enzyme required for DNA synthesis.
                          Trifluridine has shown antiviral activity
                          against herpes simplex virus types 1 and 2
                          and vaccinia and activity in tissue culture
                          against some strains of adenovirus.  However,
                          it is inactive against bacteria, fungi and
                          Chlamydia. [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Used experimentally for the treatment of
                          acyclovir-resistant and foscarnet-resisitant
                          HZV infection [AmFAR Tx Dir 1995;7(4); NIAID
                          ACTG 172]
 DISEASES STUDIED/TREATED Herpes simplex, mucocutaneous (at nasal,
                          oral, vaginal, and anal openings) [AmFAR Tx
                          Dir 1995;7(4); NIAID ACTG 172]
 CLASSIFICATION CODE      Antiviral [USAN 1996]
 OTHER MAJOR USES         Herpes simplex infections that occur in the
                          eye. Approved for the treatment of epithelial
                          keratitis due to Herpes simplex virus [PDR
                          1995; AmFAR Tx Dir 1995;7(4)]
 ADVERSE EFFECTS          The most common adverse effects of ophthalmic
                          trifluridine are mild, transient burning or
                          stinging upon instillation and palpebral
                          (eyelid) edema. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity reactions or chemical
                          intolerance to trifluridine. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Occurs as a white
                          crystalline powder [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H11F3N2O5 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 296.20 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 186-189 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMEMTAL COMPOSITION:  C40.55%, H3.74%,
                          F19.24%, N9.46%, O27.01% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water and alcohol
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Commercially available
                          solution has a pH of 5.7 [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A pyrimidine nucleoside,
                          structurally related to idoxuridine and
                          thymidine [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Trifluridine differs
                          structurally from thymidine in the presence
                          of 3 fluorine atoms in place of 3 hydrogen
                          atoms in the methyl group of the latter
                          compound [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Ophthalmic solution. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Topical, applied in a thin
                          fluid layer that overlaps the edges of the
                          lesion. [PDR 1995] [NIAID ACTG 172]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: In clinical study it was
                          used in conjunction with polymyxin B/
                          bacitracin ointment which was applied over
                          the trifluridine. [PDR 1995] [NIAID ACTG 172]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 2-8 deg C (36-46 deg F).
                          [PDR 1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Balfour HH Jr, Benson C, Braun J, Cassens B,
                          Erice A, Friedman-Kien A, Klein T, Polsky B,
                          Safrin S. Management of acyclovir-resistant
                          herpes simplex and varicella-zoster virus
                          infections. J Acquir Immune Defic Syndr. 1994
                          Mar;7(3):254-60.
 REFERENCES               Murphy M, Morley A, Eglin RP, Monteiro E.
                          Topical trifluridine for mucocutaneous
                          acyclovir-resistant herpes simplex II in AIDS
                          patient [letter]. Lancet. 1992 Oct
                          24;340(8826):1040.
 REFERENCES               Kessler H, Weaver D, Benson C, Pottage J,
                          Safrin S, Nevin T, Davis R, Owens S, Korvick
                          J. ACTG 172: treatment of acyclovir-resistant
                          (ACV-R) mucocutaneous herpes simplex virus
                          (HSV) infection in patients with AIDS: open
                          label pilot study of topical trifluridine
                          (TFT). Int Conf AIDS. 1992 Jul
                          19-24;8(1):We55 (abstract no. WeB 1056).
 REFERENCES               Birch CJ, Tyssen DP, Tachedjian G, Doherty R,
                          Hayes K, Mijch A, Lucas CR. Clinical effects
                          and in vitro studies of trifluorothymidine
                          combined with interferon-alpha for treatment
                          of drug-resistant and -sensitive herpes
                          simplex virus infections. J Infect Dis. 1992
                          Jul;166(1):108-12.
 REFERENCES               Rosenwasser GO, Greene WH. Simultaneous
                          herpes simplex types 1 and 2 keratitis in
                          acquired immunodeficiency syndrome [letter].
                          Am J Ophthalmol. 1992 Jan 15;113(1):102-3.
 REFERENCES               Young TL, Robin JB, Holland GN, Hendricks RL,
                          Paschal JF, Engstrom RE Jr, Sugar J. Herpes
                          simplex keratitis in patients with acquired
                          immune deficiency syndrome. Ophthalmology.
                          1989 Oct;96(10):1476-9.
 ENTRY MONTH              9111
 LAST REVISION DATE       960612
 

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