      Document 0086
 DOCN  DRG0086
 UNIQUE IDENTIFIER        DRG-0161
 NAME OF SUBSTANCE        Fluorouracil (Topical) [USAN 1996]
 REGISTRY NUMBER          51-21-8
 STANDARD CHEMICAL NAME   2,4(1H,3H)-Pyrimidinedione, 5-fluoro- [USAN
                          1996]
 SYNONYMS                 Adrucil [USAN 1996]
 SYNONYMS                 Efudex [USAN 1996]
 SYNONYMS                 Fluoroplex [USAN 1996]
 SYNONYMS                 Ro 2-9757 [USAN 1996]
 SYNONYMS                 5-Fluorouracil [USAN 1996]
 SYNONYMS                 5-FU [USAN 1996]
 SYNONYMS                 FU [CHEMLINE]
 PROTOCOL ID NUMBERS      NIAID ACTG 200
 SECONDARY SOURCE ID      NSC-19893 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Metabolism of fluorouracil in
                          the anabolic pathway possibly blocks the
                          methylation reaction of deoxyuridylic acid to
                          thymidylic acid, thus interfering with
                          synthesis of DNA and, to a lesser extent,
                          RNA. Thus, the effect of fluorouracil may be
                          to create a thymine deficiency that provokes
                          unbalanced growth and death of cells. The
                          effects of DNA and RNA deprivation are most
                          apparent in cells that are rapidly
                          proliferating. The catabolic metabolism of
                          fluorouracil results in inactive degradative
                          products. TOPICAL APPLICATION: Human studies
                          with topical application of 14-carbon-labeled
                          fluorouracil cream or solution demonstrated
                          insignificant absorption as measured by
                          14-carbon content of plasma, urine, and
                          respiratory carbon dioxide. Only about 6
                          percent of topical fluorouracil is absorbed
                          systemically. Onset of action is usually 2 to
                          3 days. [PDR 1995] [NIAID ACTG 200] [AHFS
                          Drug Information 1995]
 DISEASES STUDIED/TREATED Vaginal application of cream to prevent
                          recurrence of cervical/vaginal dysplasia
                          [NIAID ACTG 200]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Topical treatment of multiple actinic or
                          solar keratoses; topical treatment of
                          superficial basal cell carcinomas, only if
                          conventional methods are inpractical; topical
                          treatment of intraepithelial neoplasia of
                          skin and vagina [PDR 1995] [NIAID ACTG 200]
 ADVERSE EFFECTS          Topical application: Adverse effects include
                          localized pain, pruritis, hyperpigmentation,
                          burning, allergic contact dermatitis,
                          scarring, soreness, tenderness, suppuration,
                          scaling, and swelling. Other adverse effects
                          include alopecia, insomnia, stomatitis,
                          irritability, medicinal taste,
                          photosensitivity, lacrimation,
                          telangiectasia, and urticaria. Laboratory
                          abnormalities include leukocytosis,
                          thrombocytopenia, toxic granulation, and
                          eosinophilia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          hypersensitivity to any components of the
                          product and in pregnant women. Patients
                          receiving fluorouracil topical therapy should
                          avoid exposure to sunlight or other
                          ultraviolet rays. [PDR 1993] [NIAID ACTG 200]
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Fluorinated pyrimidine [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C4H3FN2O2 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 130.08 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C36.93%, H2.32%,
                          F14.61%, N21.54%, O24.60% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Sparingly soluble in water;
                          slightly soluble in alcohol [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa: 8.0 and 13.0 [USP DI
                          1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to practically
                          white crystalline powder [PDR 1991]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Cream 1% or 5%, solution 1%, 2%,
                          or 5%. [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Topical (cream or
                          solution). [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store between 15-30 C (59-86 F).
                          Protect from freezing. Store in tight
                          container. [AHFS Drug Information 1995]
 MANUFACTURERS            Hoffmann-La Roche Pharmaceutical Company
 REFERENCES               Clark JW, Beitz J, Cummings F, Sikov W,
                          Browne M, Akerley W, Wanebo H, Weitberg AB,
                          Kennedy T, Bigley J, Darnowski JD. Phase II
                          Study of 5-fluorouracil (5-FU), leucovorin
                          (LV) and azidodeoxythymidine (AZT) in
                          patients with metastatic colorectal cancer
                          (Meeting abstract). Proc Annu Meet Am Soc
                          Clin Oncol; 14:A557 1995.
 REFERENCES               Marchbanks K, Dudley MN, Posner MR, Darnowski
                          J. Pharmacokinetics and pharmacodynamics of
                          high-dose zidovudine administered as a
                          continuous infusion in patients with cancer.
                          Pharmacotherapy. 1995 Jul-Aug;15(4):451-7.
 REFERENCES               Miyazaki K, Mizutani H, Katabuchi H, Fukuma
                          K, Fujisaki S, Okamura H. Activated (HLA-DR+)
                          T-lymphocyte subsets in cervical carcinoma
                          and effects of radiotherapy and immunotherapy
                          with sizofiran on cell-mediated immunity and
                          survival. Gynecol Oncol. 1995
                          Mar;56(3):412-20.
 REFERENCES               Smith DE, Shah KH, Rao AR, Frost DB, Latino
                          F, Anderson PJ, Peddada AV, Kagan AR. Cancer
                          of the anal canal: treatment with
                          chemotherapy and low-dose radiation therapy.
                          Radiology. 1994 May;191(2):569-72.
 REFERENCES               Chadha M, Rosenblatt EA, Malamud S, Pisch J,
                          Berson A. Squamous-cell carcinoma of the anus
                          in HIV-positive patients. Dis Colon Rectum.
                          1994 Sep;37(9):861-5.
 REFERENCES               Smith D, Shah K, Rao AR, Frost D, Kagan AR,
                          Pedadda AV. Results of chemo-radiation
                          treatment for epidermoid cancer of the anal
                          canal (Meeting abstract). Proc Annu Meet Am
                          Soc Clin Oncol. 1993;12:A683.
 REFERENCES               Williams PS, Mun C. Response of dermal
                          epidemic Kaposi's sarcoma to concomitant
                          topical 5-fluorouracil and radiation therapy:
                          results of a pilot study (Meeting abstract).
                          American Radium Society's 75th Annual
                          Meeting. April 24-28, 1993, Aruba, p.35.
 REFERENCES               Conant W, Illeman M, Michaud A, Irey D,
                          Orenberg E. Treatment of Kaposi's sarcoma
                          with intralesional MPI 5003 FU (fluorouracil
                          therapeutic implants. Int Conf AIDS. 1993 Jun
                          6-11;9(1):402 (abstract no. PO-B12-1602).
 REFERENCES               Jaiyesimi IA, Pazdur R. Cisplatin and
                          5-fluorouracil as salvage therapy for
                          recurrent metastatic squamous cell carcinoma
                          of the anal canal [clinical conference]. Am J
                          Clin Oncol. 1993 Dec;16(6):536-40.
 REFERENCES               Brodman M, Dottino P, Friedman F Jr, Heller
                          D, Bleiweiss I, Sperling R. Human
                          papillomavirus-associated lesions of the
                          vagina and cervix. Treatment with a laser and
                          topical 5-fluorouracil. J Reprod Med. 1992
                          May;37(5):453-6.
 ENTRY MONTH              9301
 LAST REVISION DATE       960308
 

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