      Document 0063
 DOCN  DRG0063
 UNIQUE IDENTIFIER        DRG-0184
 NAME OF SUBSTANCE        Thalidomide [USAN 1996]
 REGISTRY NUMBER          50-35-1
 STANDARD CHEMICAL NAME   2-(2,6-Dioxo-3-piperidinyl)-1H-isoindole-1,3
                          (2H)-dione [Merck Index 1989]
 SYNONYMS                 N-(2,6-Dioxo-3-piperidinyl) phthalimide
                          [Merck Index 1989]
 SYNONYMS                 Alpha-phthalimidoglutarimide [Merck Index
                          1989]
 SYNONYMS                 3-phthalimidoglutarimide [Merck Index 1989]
 SYNONYMS                 2,6-dioxo-3-phthalimidopiperidine [Merck
                          Index 1989]
 SYNONYMS                 N-phthalylglutamic acid imide [Merck Index
                          1989]
 SYNONYMS                 N-phthaloylglutamimide [Merck Index 1989]
 SYNONYMS                 K-17 [Merck Index 1989]
 SYNONYMS                 Distaval [Merck Index 1989]
 SYNONYMS                 Softenon [Merck Index 1989]
 SYNONYMS                 Sedalis [Merck Index 1989]
 SYNONYMS                 Talimol [Merck Index 1989]
 SYNONYMS                 Pantosediv [Merck Index 1989]
 SYNONYMS                 Neurosedyn [Merck Index 1989]
 SYNONYMS                 Kevadon [USAN 1996]
 SYNONYMS                 Contergan [Merck Index 1989]
 SYNONYMS                 Synovir [Celgene Corporation]
 PROTOCOL ID NUMBERS      FDA 133A
 PROTOCOL ID NUMBERS      FDA 230A
 PROTOCOL ID NUMBERS      NIAID ACTG 251
 PROTOCOL ID NUMBERS      NIAID ACTG 267
 PROTOCOL ID NUMBERS      NIAID IL-2/TNF ANTAG.
 PROTOCOL ID NUMBERS      FDA 230B
 PROTOCOL ID NUMBERS      NCI 96 C-4
 SECONDARY SOURCE ID      NSC-66847 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Thalidomide probably has a
                          direct effect on the immune system since it
                          has no antibacterial activity yet seems to be
                          effective against some bacterial infections.
                          The immunomodulatory effect of thalimide is
                          currently unknown. The possibility that the
                          administration of this compound will
                          accelerate the deterioration of the
                          immunologic status of HIV patients cannot be
                          excluded. [Drug Saf 1992 Mar-Apr;7(2)]
 DISEASES STUDIED/TREATED Current being studied for possible treatment
                          of mycobacterium infection and wasting
                          syndrome in HIV infection [FDA 133A] [FDA
                          230A]
 DISEASES STUDIED/TREATED Successful results have been reported in
                          treatment of various ulcerations including
                          recurrent aphthous stomatitis (RAS) [DICP
                          1990 Nov;24(11)] [AIDS Therapies 1995 Sep]
 CLASSIFICATION CODE      Immunomodulator [Drug Saf. 1992 Mar-Apr;7(2)]
 CLASSIFICATION CODE      Sedative [Merck Index 1989]
 CLASSIFICATION CODE      Hypnotic [Merck Index 1989]
 OTHER MAJOR USES         Previously used drug that was withdrawn from
                          market because of association with fetal
                          abnormalities. Orphan drug indication for
                          treatment of graft vs. host disease and
                          transplant rejection. Thalidomide is the
                          treatment of choice for type 2 leprosy
                          reactions and is available only for this
                          investigational use in the U.S. [Facts and
                          Comparisons 1995] [Drug Saf 1992
                          Mar-Apr;7(2)] [USP DI 1995]
 ADVERSE EFFECTS          Thalidomide can induce severe congenital
                          abnormalities in developing fetuses. The most
                          common side effects are sedation and
                          constipation; it can also induce
                          neurotoxicity. [AmFAR Tx Dir 1995;7(4)] [Drug
                          Saf 1992 Mar-Apr;7(2)] [Arch Dermatol
                          1990;126]
 CONTRAINDICATIONS        Except under unusual circumstances,
                          thalidomide is contraindicated in women of
                          child bearing age who might conceive during
                          therapy. Should not be used in patients with
                          pre-existing HIV related peripheral
                          polyneuropathy, polyradiculopathy, or
                          encephalopathy. [Drug Evaluations Annual
                          1992] [Drug Saf 1992 Mar-Apr;7(2)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C13H10N2O4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 258.23 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 269-271 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C60.46% H3.90% N10.85%
                          O24.78% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Sparingly soluble in water,
                          methanol, ethanol, acetone, ethyl acetate,
                          butyl acetate, glacial acetic acid. Very
                          soluble in dioxane, DMF, and pyridine.
                          Practically insoluble in ether, chloroform,
                          and benzene [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: UV max (neutral solution)
                          220-300 nm [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [AmFAR Tx Dir
                          1995;7(4)]
 MANUFACTURERS            Celgene Corporation
 REFERENCES               Tramontana JM, Utaipat U, Molloy A, Akarasewi
                          P, Burroughs M, Makonkawkeyoon S, Johnson B,
                          Klausner JD, Rom W, Kaplan G. Thalidomide
                          treatment reduces tumor necrosis factor alpha
                          production and enhances weight gain in
                          patients with pulmonary tuberculosis. Mol Med
                          1995 May;1(4):384-97.
 REFERENCES               Paterson DL, Georghiou PR, Allworth AM, Kemp
                          RJ. Thalidomide as treatment of refractory
                          aphthous ulceration related to human
                          immunodeficiency virus infection. Clin Infect
                          Dis 1995 Feb;20(2)250-4.
 REFERENCES               Eriksson T, Bjorkman S, Roth B, Fyge A,
                          Hoglund P. Stereospecific determination,
                          chiral inversion in vitro and
                          pharmacokinetics in humans of the enantiomers
                          of thalidomide. Chirality 1995;7(1):44-52.
 REFERENCES               Kaplan G. Cytokine regulation of disease
                          progression in leprosy and tuberculosis.
                          Immunology 1994 Oct;191(4-5):564-8.
 REFERENCES               Reyes-Teran G, Sierra-Madero JG, Martinez del
                          Cerro V, Munoz-Trejo T, Arroyo-Figueroa H,
                          Pasquetti A, Calva JJ, Ruiz-Palacios GM.
                          Effects of thalidomide on wasting syndrome in
                          patients with AIDS. A randomized,
                          double-blind, placebo controlled clinical
                          trial. Int Conf AIDS. 1994 Aug 7-12;10(2):65
                          (abstract no. 536B).
 REFERENCES               Klausner JD, Makonkawkeyoon S, Akarasewi P,
                          Kasinrerk W, Nakata K, Kaplan G. Treatment
                          with thalidomide with AIDS patients. Int Conf
                          AIDS. 1994 Aug 7-12;10(1):221 (abstract no.
                          PBO312).
 REFERENCES               Ball SC, Sepkowitz KA, Jacobs JL. Thalidomide
                          for treatment of aphthous ulcers in patients
                          with HIV. Int Conf AIDS. 1994 Aug
                          7-12;10(1):224 (abstract no. PBO327).
 REFERENCES               Ochonisky S, Verroust J, Bastuji-Garin S,
                          Gherardi R, Revuz J. Thalidomide neuropathy
                          incidence and clinico-electrophysiologic
                          findings in 42 patients. Arch Dermatol. 1994
                          Jan;130(1):66-9.
 REFERENCES               Vosgerau JC. Autoimmunity in human
                          immunodeficiency virus infection and the use
                          of thalidomide [editorial]. Panminerva Med.
                          1994 Mar;36(1):1-4.
 REFERENCES               Makonkawkeyoon S, Limson-Pobre RN, Moreira
                          AL, Schauf V, Kaplan G. Thalidomide inhibits
                          the replication of human immunodeficiency
                          virus type 1. Proc Natl Acad Sci USA. 1993
                          Jul 1;90(13):5974-8.
 ENTRY MONTH              9307
 LAST REVISION DATE       960612
 

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