      Document 0051
 DOCN  DRG0051
 UNIQUE IDENTIFIER        DRG-0196
 NAME OF SUBSTANCE        Ethionamide [USAN 1996]
 REGISTRY NUMBER          536-33-4
 STANDARD CHEMICAL NAME   2-Ethyl-4-pyridinecarbothioamide [Merck Index
                          1989]
 SYNONYMS                 Amidazine [Merck Index 1989]
 SYNONYMS                 Ethioniamide [Merck Index 1989]
 SYNONYMS                 Bayer 5312 [Merck Index 1989]
 SYNONYMS                 1314 Th [Merck Index 1989]
 SYNONYMS                 Nisotin [Merck Index 1989]
 SYNONYMS                 Trecator [Merck Index 1989]
 SYNONYMS                 Trecator-SC [USAN 1996]
 SYNONYMS                 Trescatyl [Merck Index 1989]
 SYNONYMS                 Aetina [Merck Index 1989]
 SYNONYMS                 Ethimide [Merck Index 1989]
 SYNONYMS                 Iridocin [Merck Index 1989]
 SYNONYMS                 Tio-Mid [Merck Index 1989]
 SYNONYMS                 2-Ethylthioisonicotinamide [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: May be bacteriostatic or
                          bactericidal in action depending on drug
                          concentration at the site of infection and
                          the susceptibility of the infecting organism.
                          Appears to inhibit peptide synthesis in
                          susceptible organisms. Active only against
                          organisms of the genus Mycobacterium, such as
                          M. tuberculosis, M. bovis, M. kansasii, and
                          some strains of M. avium and M.
                          intracellulare. Resistant strains of
                          initially susceptible M. tuberculosis develop
                          rapidly if ethionamide is used alone or in
                          the treatment of clinical tuberculosis. There
                          is no evidence of cross resistance between
                          ethionamide and other antituberculosis agents
                          used in the US. Rapidly absorbed from the
                          intestinal tract following oral
                          administration. Bioavailability ca. 100%.
                          Widely distributed to most tissues and
                          fluids. Concentration in various organs and
                          CSF approximately equal to plasma
                          concentrations. Readily crosses placenta.
                          Metabolized to sulfoxide, which is active,
                          and to inactive metabolites. Half-life is 2-3
                          hours. Peak serum concentration is ca. 2.2
                          mcg/ml after single 500 mg oral dose.
                          Elimination is through the kidneys. [AHFS
                          Drug Information 1995] [Drug Evaluations
                          Annual 1995]
 DISEASES STUDIED/TREATED Used as a second-line agent against
                          tuberculosis in the HIV-infected person
                          [NIAID ACTG 238] [Drug Evaluations Annual
                          1995]
 DISEASES STUDIED/TREATED It should be given only with other effective
                          antituberculosis drugs [NIAID ACTG 238] [Drug
                          Evaluations Annual 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Tuberculosis; leprosy [PDR 1995] [AHFS Drug
                          Information 1995]
 ADVERSE EFFECTS          Ethionamide almost invariably causes
                          gastrointestinal disturbances, most
                          frequently anorexia, nausea and vomiting.
                          Other adverse effects similar to those seen
                          with isoniazid have been reported, such as
                          peripheral neuritis, optic neuritis, psychic
                          disturbances (including mental depression),
                          postural hypotension, skin rashes,
                          thrombocytopenia, pellagra-like syndrome,
                          jaundice and/or hepatitis, increased
                          difficulty in management of diabetes
                          mellitus, stomatitis, gynecomastia, and
                          impotence. A metallic taste in the mouth has
                          also been noted. [Drug Evaluations Annual
                          1995] [PDR 1995] [NIAID ACTG 238]
 CONTRAINDICATIONS        Contraindicated in patients who develop
                          severe hypersensitivity reactions and severe
                          hepatic damage. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: Antibacterial (tuberculostatic)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C8H10N2S [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 166.24 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 162 C [PDR 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Very sparingly soluble in water
                          and ether. Sparingly soluble in methanol,
                          ethanol, and propylene glycol. Soluble in hot
                          acetone and dichlorethane [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Stable at ordinary temperatures
                          and humidities [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Yellow, crystalline,
                          nonhygroscopic compound with a
                          faint-to-moderate sulfide odor [PDR 1995]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C57.80%, H6.06%,
                          N16.85%, S19.29% [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 250 mg tablets. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Keep tightly closed. [PDR 1995]
 MANUFACTURERS            Wyeth-Ayerst Laboratories
 REFERENCES               Stone MM, Vannier AM, Storch SK, Peterson C,
                          Nitta AT, Zhang Y. Brief report: meningitis
                          due to iatrogenic BCG infection in two
                          immunocompromised children. N Engl J Med 1995
                          Aug 31;333(9):561-3.
 REFERENCES               Heym B, Honore N, Truffot-Pernot C, Banerjee
                          A, Schurra C, Jacobs WR Jr,van Embden JD,
                          Grosset JH, Cole ST. Implications of
                          multidrug resistance for the future of
                          short-course chemotherapy of tuberculosis: a
                          molecular study [see comments]. Lancet. 1994
                          Jul30;344(8918):293-8.
 REFERENCES               Heifets LB. Antimycobacterial drugs. Semin
                          Respir Infect. 1994 Jun;9(2):84-103.
 REFERENCES               Banerjee A, Dubnau E, Quemard A,
                          Balasubramanian V, Um KS, Wilson T, Collins
                          D, de Lisle G, Jacobs WR Jr. inhA, a gene
                          encoding a target for isoniazid and
                          ethionamide in Mycobacterium tuberculosis
                          [see comments]. Science 1994 Jan
                          14;263(5144):227-30.
 REFERENCES               Rose DN, Weltman A. Antibiotic sensitivity
                          pattern of Mycobacterium tuberculosis in a
                          population with high prevalence of AIDS and
                          antibiotic resistance; implications for
                          choosing therapeutic regimens. Int Conf AIDS.
                          1993 Jun 6-11;9(1):52 (abstract no.
                          WS-B09-5).
 REFERENCES               Edlin BR, Attoe LS, Grieco MH, Williams J,
                          Schneider N, Gilligan ME. Recognition and
                          treatment of primary multidrug-resistant
                          tuberculosis (MDRTB) in HIV-infected
                          patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):52 (abstract no. WS-B09-6).
 REFERENCES               Peloquin CA. Pharmacology of the
                          antimycobacterial drugs. Med Clin North Am.
                          1993 Nov;77(6):1253-62.
 REFERENCES               Kwan R, Chiliade P, Sharp V. Report of two
                          cases of MDR-MTB pneumonia in
                          non-immunocompromised health care workers
                          (HCWs) at a New York City AIDS center. Int
                          Conf AIDS. 1993 Jun 6-11;9(1):329 (abstract
                          no. PO-B07-1162).
 REFERENCES               Rastogi N, Goh KS, Guillou N, Labrousse V.
                          Spectrum of drugs against atypical
                          mycobacteria: how valid is the current
                          practice of drug susceptibility testing and
                          the choice of drugs? Int J Med Microbiol
                          Virol Parasitol Infect Dis. 1992
                          Dec;277(4):474-84.
 REFERENCES               From the Centers for Disease Control.
                          Transmission of multidrug-resistant
                          tuberculosis among immunocompromised persons,
                          correctional system--New York, 1991. JAMA.
                          1992 Aug 19;268(7):855-6.
 ENTRY MONTH              9403
 LAST REVISION DATE       960417
 

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