      Document 0100
 DOCN  DRG0100
 UNIQUE IDENTIFIER        DRG-0147
 NAME OF SUBSTANCE        Tretinoin [USAN 1996]
 REGISTRY NUMBER          302-79-4
 RELATED REGISTRY NUMBER  7005-78-9
 RELATED REGISTRY NUMBER  56573-65-0
 RELATED REGISTRY NUMBER  120242-93-5
 RELATED REGISTRY NUMBER  13497-05-7
 RELATED REGISTRY NUMBER  22232-80-0
 STANDARD CHEMICAL NAME   3,7 - Dimethyl -9- (2,6,6
                          -trimethyl-1-cyclohexen-1-yl) -2,4,6,8
                          -nonatetraenoic acid [Merck Index 1989]
 SYNONYMS                 all-trans-Retinoic acid [USAN 1996]
 SYNONYMS                 all-trans-Tretinoin [CHMELINE]
 SYNONYMS                 all-trans-Vitamin A acid [CHEMLINE]
 SYNONYMS                 (all-E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyc-
                          lohexen-1-yl)-2,4,6,8-nonatetraenoic acid
                          [CHEMLINE]
 SYNONYMS                 Airol [Merck Index 1989]
 SYNONYMS                 Aberel [Merck Index 1989]
 SYNONYMS                 Aknoten [Merck Index 1989]
 SYNONYMS                 beta-All-trans-Retinoic Acid [CHEMLINE]
 SYNONYMS                 beta-RA [CHEMLINE]
 SYNONYMS                 beta-Retinoic acid [CHEMLINE]
 SYNONYMS                 Cordes Vas [Merck Index 1989]
 SYNONYMS                 Dermairol [Merck Index 1989]
 SYNONYMS                 Effederm [Merck Index 1989]
 SYNONYMS                 Epi-Aberal [Merck Index 1989]
 SYNONYMS                 Eudyna [Merck Index 1989]
 SYNONYMS                 HSDB 2169 [CHEMLINE]
 SYNONYMS                 Retin-A [PDR 1995]
 SYNONYMS                 Retinoic acid [USAN 1996]
 SYNONYMS                 Retinoic acid, all-trans- [CHEMLINE]
 SYNONYMS                 Stieva-A [USP DI 1995]
 SYNONYMS                 trans-Retinoic Acid [CHEMLINE]
 SYNONYMS                 Tretin M [CHEMLINE]
 SYNONYMS                 Tretinoin, all-trans- [CHEMLINE]
 SYNONYMS                 Tretinoino [CHEMLINE]
 SYNONYMS                 Tretinoinum [CHEMLINE]
 SYNONYMS                 Vitamin A acid [Merck Index 1989]
 SYNONYMS                 Vitamin A acid, all-trans- [CHEMLINE]
 SYNONYMS                 Vitamin A1 acid, all-trans- [CHEMLINE]
 PROTOCOL ID NUMBERS      NCI 92 C-146
 PROTOCOL ID NUMBERS      NCI 95 C-144
 SECONDARY SOURCE ID      NSC-122758 [CHEMLINE]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Tretinoin is a major
                          endogenous metabolite of vitamin A which
                          induces differentiation and/or growth
                          inhibition in many tumorogenic cell lines,
                          including KS cells in culture. Tretinoin has
                          been shown to decrease HIV replication in
                          chronically infected macrophages, monocytic
                          and T cell lines and conversely to promote
                          HIV replication in macrophages and monocytic
                          cell lines recently infected. Possibly
                          decreases cohesiveness of follicular
                          epithelial cells with decreased microcomedo
                          formation. Additionally, tretinoin stimulates
                          mitotic activity and increased turnover of
                          follicular epithelial cells causing extrusion
                          of the comedones. [Int Conf AIDS 1993 Jun
                          6-11;9(1):(abstract no. PO-B12-1571)] [Int
                          Conf AIDS 1993 Jun 6-11;9(1):(abstract no.
                          PO-A25-0621)] [PDR 1995]
 DISEASES STUDIED/TREATED Under investigation for treatment of Kaposi's
                          sarcoma [AmFAR Tx Dir 1995;7(4)] [J Clin
                          Oncol 1995 May;13(5)]
 CLASSIFICATION CODE      Keratolytic [USAN 1996]
 OTHER MAJOR USES         Acne vulgaris [PDR 1995]
 SUBSTANCE INTERACTIONS   Caution should be exercised with concomitant
                          use of topical medication; medicated or
                          abrasive soaps and cleansers; soaps and
                          cosmetics that have a strong drying effect;
                          products with high concentrations of alcohol,
                          astringents, spices, or lime; and
                          particularly preparations containing sulfur,
                          resorcinol, or salicylic acid. [PDR 1995]
 ADVERSE EFFECTS          Adverse effects with topical administration
                          include swelling or cracking of lips;
                          headaches; dryness of skin, mouth or eyes;
                          fatigue; loss of appetite; nausea or
                          vomiting; visual problems; nasal congestion
                          or nose bleeds; skin rashes; itching; aching
                          discomfort of bones or joints; increased
                          blood triglyceride levels; and increased
                          pressure in the brain. Adverse effects
                          reported with oral administration include
                          severe nausea and vomiting, headaches, rash,
                          generalized malaise, hypercalcemia,
                          pancreatitis, dryness of the skin, myalgia,
                          and increases in liver enzyme activity. [Int
                          Conf AIDS 1993 Jun 6-11;9(1):(abstract no.
                          PO-B12-1571] [Int Conf AIDS 1993 Jun
                          6-11;9(1):(abstract no. PO-B12-1562)] [PDR
                          1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity to any of the product
                          ingredients. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The natural acid derivative
                          of vitamin A, it is a potent regulator of
                          epithelial differentiation within many
                          neoplastic cell systems [AmFAR Tx Dir
                          1995;7(4)]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Yellow to light orange,
                          crystalline powder [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C20H28O2 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 300.44 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 180-182 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C79.95%, H9.39%,
                          O10.65% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Insoluble in water, slightly
                          soluble in alcohol [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 0.025% and 0.01% gel; 0.025%,
                          0.05%, and 0.1% cream; and 0.05% liquid. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Topical; Oral. [Int Conf
                          AIDS 1993 Jun 6-11;9(1): (abstract no.
                          PO-B12-1571)] [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Liquid and gel: store below 86 F.
                          Cream: store below 80 F. [PDR 1995]
 MANUFACTURERS            Genentech, Incorporated
 REFERENCES               Bailey J, Pluda JM, Foli A, Saville MW, Bauza
                          S, Adamson PC, Murphy RF, Cohen RB, Broder S,
                          Yarchoan R. Phase I/II study of intermittent
                          all-trans-retinoic acid, alone and in
                          combination with interferon alfa-2a, in
                          patients with epidemic Kaposi's sarcoma. J
                          Clin Oncol. 1995 Aug;13(8):1966-74.
 REFERENCES               Adamson PC, Bailey J, Pluda J, Poplack DG,
                          Bauza S, Murphy RF, Yarchoan R, Balis FM.
                          Pharmacokinetics of all-trans-retinoic acid
                          administered on an intermittent schedule. J
                          Clin Oncol. 1995 May;13(5):1238-41.
 REFERENCES               Bonhomme L, Fredj G, Ecstein E, Maurisson G,
                          Farabos C, Misset JL, Jasmin C. Treatment of
                          AIDS-associated Kaposi's sarcoma with oral
                          tretinoin. Am J Hosp Pharm. 1994 Oct
                          1;51(19):2417-9.
 REFERENCES               Gill PS, Espina BM, Moudgil T, Kidane S,
                          Esplin JA, Tulpule A, Levine AM. All-trans
                          retinoic acid for the treatment of
                          AIDS-related Kaposi's sarcoma: results of a
                          pilot phase II study. Leukemia. 1994;8 Suppl
                          3:S26-32.
 REFERENCES               Von Roenn J, von Gunten C, Mullane M, French
                          S, Blough R, Benson AB 3d. All-transretinoic
                          acid (TRA) in the treatment of AIDS-related
                          Kaposi's sarcoma. Int Conf AIDS 1993 Jun
                          6-11;9(1):397 (abstract no. PO-B12-1571).
 REFERENCES               Dubreuil-Lemaire ML, Bourgault I, Levy Y,
                          Venet A, Deforges L, Sobel A. In vivo effects
                          of retinoic acid on HIV replication in CD4(+)
                          fresh cells from HIV infected patients. Int
                          Conf AIDS 1993 Jun 6-11;9(1):238 (abstract
                          no. PO-A25-0621).
 REFERENCES               Fauci AS. Pharmacologic regulation of HIV
                          expression. AIDS Res Hum Retroviruses. 1992
                          May;8(5):707-10.
 REFERENCES               Bonhomme L, Fredj G, Averous S, Szekely AM,
                          Ecstein E, Trumbic B, Meyer P, Lang JM,
                          Misset JL, Jasmin C. Topical treatment of
                          epidemic Kaposi's sarcoma with
                          all-trans-retinoic acid [letter]. Ann Oncol.
                          1991 Mar;2(3):234-5.
 REFERENCES               Bonhomme L, Fredj G, Averous S, Szekely AM,
                          Meyer P, Ecstein E, Lang JM, Trumbic B,
                          Misset JL, Jasmin C. Topically applied All
                          Trans-Retinoic acid for the treatment of
                          Kaposi's sarcoma (Ks). Int Conf AIDS. 1990
                          Jun 20-23;6(2):376 (abstract no. 2090).
 ENTRY MONTH              9210
 LAST REVISION DATE       960514
 

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