      Document 0124
 DOCN  DRG0124
 UNIQUE IDENTIFIER        DRG-0123
 NAME OF SUBSTANCE        Isoniazid [USAN 1996]
 REGISTRY NUMBER          54-85-3
 STANDARD CHEMICAL NAME   4-Pyridinecarboxylic acid hydrazide [USAN
                          1996]
 SYNONYMS                 Rimitsid [Merck Index 1989]
 SYNONYMS                 INH-Burgthal [Merck Index 1989]
 SYNONYMS                 Neoxin [Merck Index 1989]
 SYNONYMS                 Hyzyd [Merck Index 1989]
 SYNONYMS                 Isonicazide [Merck Index 1989]
 SYNONYMS                 Tibiazide [Merck Index 1989]
 SYNONYMS                 Isotebezid [Merck Index 1989]
 SYNONYMS                 Nitadon  [Merck Index 1989]
 SYNONYMS                 Sauterazid [Merck Index 1989]
 SYNONYMS                 Hydrazid [Merck Index 1989]
 SYNONYMS                 Mybasan [Merck Index 1989]
 SYNONYMS                 Nicozide [Merck Index 1989]
 SYNONYMS                 Nicotibina [Merck Index 1989]
 SYNONYMS                 INH [Merck Index 1989]
 SYNONYMS                 Cedin (Aerosol) [Merck Index 1989]
 SYNONYMS                 Isocid [Merck Index 1989]
 SYNONYMS                 Hidrasonil [Merck Index 1989]
 SYNONYMS                 Laniazid [Merck Index 1989]
 SYNONYMS                 Nyscozid [Merck Index 1989]
 SYNONYMS                 Retozide [Merck Index 1989]
 SYNONYMS                 Niplen [Merck Index 1989]
 SYNONYMS                 Ditubin [Merck Index 1989]
 SYNONYMS                 Neoteben [Merck Index 1989]
 SYNONYMS                 Niadrin [Merck Index 1989]
 SYNONYMS                 Isonicotinylhydrazine [Merck Index 1989]
 SYNONYMS                 Ertuban [Merck Index 1989]
 SYNONYMS                 Antimicina [Merck Index 1989]
 SYNONYMS                 Isonex [Merck Index 1989]
 SYNONYMS                 Unicozyde [Merck Index 1989]
 SYNONYMS                 Zonazide [Merck Index 1989]
 SYNONYMS                 Hycozid [Merck Index 1989]
 SYNONYMS                 Niconyl [Merck Index 1989]
 SYNONYMS                 Isonicid [Merck Index 1989]
 SYNONYMS                 Isonicotan [Merck Index 1989]
 SYNONYMS                 Tubazid [Merck Index 1989]
 SYNONYMS                 Isobicina [Merck Index 1989]
 SYNONYMS                 Isonilex [Merck Index 1989]
 SYNONYMS                 Isonindon [Merck Index 1989]
 SYNONYMS                 Nicetal [Merck Index 1989]
 SYNONYMS                 Nikozid [Merck Index 1989]
 SYNONYMS                 Pelazid [Merck Index 1989]
 SYNONYMS                 Raumanon [Merck Index 1989]
 SYNONYMS                 Tebecid [Merck Index 1989]
 SYNONYMS                 Tisiodrazida [Merck Index 1989]
 SYNONYMS                 Tizide [Merck Index 1989]
 SYNONYMS                 Isozyd [Merck Index 1989]
 SYNONYMS                 TB-Vis [Merck Index 1989]
 SYNONYMS                 Tekazin [Merck Index 1989]
 SYNONYMS                 Isidrina [Merck Index 1989]
 SYNONYMS                 Nevin [Merck Index 1989]
 SYNONYMS                 Continazine [Merck Index 1989]
 SYNONYMS                 Nydrazid [Merck Index 1989]
 SYNONYMS                 Dinacrin [Merck Index 1989]
 SYNONYMS                 Pyricidin [Merck Index 1989]
 SYNONYMS                 Pycazide [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 177
 PROTOCOL ID NUMBERS      NIAID ACTG 222
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 PROTOCOL ID NUMBERS      NIAID CPCRA 004
 PROTOCOL ID NUMBERS      NIAID DATRI 008
 PROTOCOL ID NUMBERS      NIAID CPCRA 005
 PROTOCOL ID NUMBERS      NIAID ACTG 309
 SECONDARY SOURCE ID      RP5015 [Merck Index 1989]
 SECONDARY SOURCE ID      FSR-3 [Merck Index 1989]
 SECONDARY SOURCE ID      RU-EF-Tb [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION:  May be bacteriostatic or
                          bactericidal depending on the concentration
                          attained at the site of infection and the
                          susceptibility of the infecting organism. INH
                          activity is limited to mycobacterium; it is
                          bacteriostatic for resting bacilli and
                          bactericidal for rapidly dividing organisms.
                          Although not fully elucidated, several
                          mechanisms of action including interference
                          with the metabolism of bacterial proteins,
                          nucleic acids, carbohydrates and lipids have
                          been proposed. One principal action of the
                          drug appears to be inhibition of mycolic acid
                          synthesis in susceptible bacteria which
                          results in loss of acid-fastness and
                          disruption of the bacterial cell wall.
                          Isoniazid is completely and rapidly absorbed
                          orally and parenterally and peaks in blood
                          levels within 1 to 2 hours. These levels
                          decline by less than or equal to 50% within 6
                          hours. Absorption rate and extent are
                          decreased by food.  It diffuses readily into
                          all body fluids (including cerebrospinal,
                          pleural, and ascitic), tissues, organs, and
                          excreta (saliva, sputum, feces). It passes
                          through the placental barrier and into breast
                          milk in concentrations comparable to those in
                          plasma. The half-life is widely variable and
                          dependent on acetylator status (i.e., one
                          hour in fast acetylators to three hours in
                          slow acetylators).  The average concentration
                          of active INH in the circulation of fast
                          acetylators is about 30 to 50 percent of the
                          concentrations in persons who acetylate the
                          drug slowly.  INH is primarily acetylated by
                          the liver; the process is genetically
                          controlled and dependent on race, but not on
                          age or sex (i.e., approximately 50% of Blacks
                          and Caucasians are slow acetylators and the
                          rest are rapid acetylators and the majority
                          of Eskimos and Orientals are rapid
                          acetylators). Liver disease can prolong the
                          clearance of isoniazid. Several minor
                          metabolites have been identified and one
                          (monoacetylhydrazine is suspected) may be
                          more reactive and responsible for liver
                          damage. Acetylation rate does not alter the
                          effectiveness of the drug. Slow acetylation
                          may lead to increased blood levels and thus
                          more toxic reactions.  Fast acetylators may
                          be more likely to develop hepatitis since
                          hepatoxicity is caused by the acetylated
                          metabolite of INH, but this remains
                          controversial. [AHFS Drug Information 1995]
                          [NIAID ACTG 177] [Facts and Comparisons 1995]
 PHARMACOLOGICAL ACTION   50 to 70% of a dose is excreted as unchanged
                          drug and metabolites by kidneys within 24
                          hours; but elimination is independent of
                          renal function. However, slow inactivators
                          may develop toxic levels in the presence of
                          impaired renal function. [AHFS Drug
                          Information 1995] [NIAID ACTG 177] [Facts and
                          Comparisons 1995]
 DISEASES STUDIED/TREATED An antibiotic which, in combination regimens,
                          is standard for the treatment and prophylaxis
                          of tuberculosis in the HIV infected patient
                          [AHFS Drug Information 1995] [NIAID ACTG 177]
 DISEASES STUDIED/TREATED Administered concurrently with pyridoxine
                          (vitamin B6) to prevent the peripheral
                          neuropathy as well as nearly all other
                          nervous system disorders attributable to
                          isoniazid (INH) [AHFS Drug Information 1995]
                          [NIAID ACTG 177]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Tuberculosis, treatment; prevention in
                          specific situations [USP DI 1995]
 SUBSTANCE INTERACTIONS   Interacts with alcohol, aluminum salts,
                          anticoagulants (oral), benzodiazepines,
                          carbamazepine, cycloserine, disulfiram,
                          enflurane, halothane, hydantoins,
                          ketoconazole, meperidine, and rifampin.
                          [Facts and Comparisons 1995]
 ADVERSE EFFECTS          The most common reaction is peripheral
                          neuropathy. It is dose related, occurs most
                          often in the malnourished and in those
                          predisposed to neuritis, and is usually
                          preceded by paresthesias of the feet and
                          hands. Other reactions include rash, fever,
                          jaundice, hematological reactions,
                          vasculitis, arthritic symptoms, convulsions,
                          mental abnormalities, xerostomia, epigastric
                          distress, methemoglobinemia, tinnitus, and
                          urinary retention. Hepatitis (age-related and
                          risk increased with daily consumption of
                          alcohol) may occur or develop even after many
                          months of treatment.  Additional adverse
                          reactions include elevated serum transaminase
                          levels (AST, ALT), bilirubinemia,
                          bilirubinuria, pyridoxine deficiency,
                          pellagra, hyperglycemia, metabolic acidosis,
                          and gynecomastia. [PDR 1995] [Facts and
                          Comparisons 1995] [NIAID ACTG 177]
 CONTRAINDICATIONS        Contraindicated in patients who develop
                          severe hypersensitivity reactions including
                          drug-induced hepatitis; also contraindicated
                          in those with previous isoniazid-associated
                          hepatic injury; severe adverse reactions to
                          isoniazid, such as fever, chills, and
                          arthritis; and acute liver disease of any
                          etiology. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Odorless, colorless or
                          white crystals or as a white, crystalline
                          powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C6H7N30 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 137.14 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT:  171.4 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION:  C52.54%, H5.15%,
                          N30.64%, O11.67% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Approximately 125 mg/ml in water
                          and 20 mg/ml in alcohol at 25 C [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY:  At low temperatures, isoniazid in
                          solution tends to crystallize and should be
                          warmed to room temperature to redissolve the
                          crystals prior to use [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pH of 1% aq solution is 5.5
                          to 6.5 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic, isonicotinic
                          acid-derivative [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (300 mg), injection (100
                          mg/ml), syrup (50 mg/5ml). [USP DI 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral, injection. [USP DI
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE: All preparations should be protected
                          from light and exposure to air and stored at
                          a temperature below 40 C and preferably
                          between 15-30 C. [USP DI 1995]
 MANUFACTURERS            Barr Laboratories Incorporated
 MANUFACTURERS            Lannett Company Incorporated
 MANUFACTURERS            Danbury Pharmacal
 REFERENCES               Jones BE, Otaya M, Antoniskis D, Sian S, Wang
                          F, Mercado A, Davidson PT, Barnes PF. A
                          prospective evaluation of antituberculosis
                          therapy in patients with human
                          immunodeficiency virus infection. Ann J
                          Respir Crit Care Med. 1994 Dec;150(6 Pt)
                          1):1499-502.
 REFERENCES               Gorbea MC, Torres F, Perez G, Paquentin J.
                          Usefulness of GM-CSF with isoniazid and
                          rifampin in the treatment of tuberculosis in
                          HIV-infected children. Int Conf AIDS. 1993
                          Jun 6-11;9(1):335 (abstract no. PO-B07-1196).
 REFERENCES               Moreno S, Baraia J, Diaz MD, Parras F, et al.
                          Preventive isoniazid among HIV-infected
                          persons with tuberculous infection. Int Conf
                          AIDS. 1993 Jun 6-11;9(1):334 (abstract no.
                          PO-B07-1193).
 REFERENCES               Wadhawan D, Hira S, Mwansa N, Sunkutu R,
                          Adera T, Perine P. Preventive tuberculosis
                          chemotherapy with isoniazid (INH) among
                          patients infected with HIV-1. Int Conf AIDS.
                          1993 Jun 6-11;9(1):321 (abstract no.
                          PO-B07-1114).
 REFERENCES               Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD
                          Jr. Effect of isoniazid prophylaxis on
                          incidence of active tuberculosis and
                          progression of HIV infection [see comments].
                          Lancet. 1993 Jul 31;342(8866):268-72.
 REFERENCES               Gutierrez MC, Cavalcante SC, Veloso VG,
                          Grinsztejn B, Moreira RB, Coletti Junior C.
                          Tuberculosis and AIDS: adverse reactions to
                          treatment. Int Conf AIDS. 1993 Jun
                          6-11;9(1):337 (abstract no. PO-B07-1211).
 REFERENCES               Rose DN, Schecter CB, Sacks HS. Preventive
                          medicine for HIV-infected patients: an
                          analysis of isoniazid prophylaxis for
                          tuberbulin reactors and for anergic patients.
                          J Gen Intern Med. 1992 Nov-Dec;7(6):589-94.
 REFERENCES               Canueto J, Torres Tortosa M, Escribano JC,
                          Perez Moreno J, Barrera A, Gonzalez M, Lucero
                          I, Lorente J, Alvarez MM. Follow-up of AIDS
                          patients with tuberculosis after completion
                          of antituberculous therapy. Is indefinite
                          isoniazide therapy advisable? Int Conf AIDS.
                          1992 Jul 19-24;8(2):B103 (abstract no. PoB
                          3100).
 REFERENCES               Pape JW, Jean S, Ho J, Haffner A, Johnson WD
                          Jr. Effect of isoniazid on the natural
                          history of HIV infection in Haiti. Int Conf
                          AIDS. 1992 Jul 19-24;8(2):B102 (abstract no.
                          PoB 3091).
 REFERENCES               Sckell B, Selwyn PA, Alcabes P, Schoenbaum E,
                          Klein R, Friedland G. High risk of active
                          tuberculosis in HIV-positive anergic drug
                          injectors; effectiveness of isoniazid
                          prophylaxis in tuberculin reactors. Int Conf
                          AIDS. 1992 Jul 19-24;8(1):Tu40 (abstract no.
                          TuC 0567).
 ENTRY MONTH              9111
 LAST REVISION DATE       960131
 

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