      Document 0136
 DOCN  DRG0136
 UNIQUE IDENTIFIER        DRG-0111
 NAME OF SUBSTANCE        Ethambutol hydrochloride [USAN 1996]
 REGISTRY NUMBER          1070-11-7
 RELATED REGISTRY NUMBER  74-55-5
 STANDARD CHEMICAL NAME   1-Butanol, 2,2'-(ethanediyldiimino)bis-,
                          dihydrochloride, (S-(R*,R*))- [USAN 1996]
 SYNONYMS                 Myambutol [USAN 1996]
 SYNONYMS                 Dexambutol [Merck Index 1989]
 SYNONYMS                 EMB-Fatol [Merck Index 1989]
 SYNONYMS                 Etibi [Merck Index 1989]
 SYNONYMS                 Etapiam [Merck Index 1989]
 SYNONYMS                 Mycobutol [Merck Index 1989]
 SYNONYMS                 (+)-2,2'-(Ethylenediimino)-di-1-butanol
                          dihydrochloride [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 135
 PROTOCOL ID NUMBERS      NIAID 92 I-165
 PROTOCOL ID NUMBERS      FDA 048D
 PROTOCOL ID NUMBERS      FDA 048E
 PROTOCOL ID NUMBERS      FDA 214
 PROTOCOL ID NUMBERS      FDA 226B
 PROTOCOL ID NUMBERS      NIAID ACTG 222
 PROTOCOL ID NUMBERS      NIAID ACTG 223
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 PROTOCOL ID NUMBERS      NIAID CPCRA 027
 PROTOCOL ID NUMBERS      DATRI 007
 PROTOCOL ID NUMBERS      NIAID ACTG 309
 SECONDARY SOURCE ID      CL 40881 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Diffuses into actively
                          growing mycobacterium cells such as tubercle
                          bacilli and appears to inhibit the synthesis
                          of one or more metabolites, thus causing
                          impairment of cell metabolism, arrest of
                          multiplication, and cell death. About 75-80%
                          of an oral dose is rapidly absorbed from the
                          gastrointestinal tract. Following a single
                          oral dose of 25 mg/kg of body weight, the
                          drug attains a peak of 2 to 5 micrograms/ml
                          in serum 2 to 4 hours after administration.
                          The serum level of the drug falls below
                          detectable levels by 24 hours after the last
                          dose except in some patients with abnormal
                          renal function. In patients with normal renal
                          function the plasma half-life is about 3.3
                          hours. In patients with renal failure the
                          half-life may be 7 hours or more.
                          Approximately 50% of the initial dose is
                          excreted in the urine, while an additional 8%
                          to 15% appears in the form of metabolites.
                          The main path of metabolism appears to be an
                          initial oxidation of the alcohol to an
                          aldehyde intermediate, followed by conversion
                          to a dicarboxylic acid. From 20-22% of the
                          initial dose is excreted in the feces as
                          unchanged drug. [PDR 1995] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Under investigation in combination therapy
                          for Mycobacterium avium complex (MAC) [AmFAR
                          Tx Dir 1995;7(4)] [NIAID ACTG 135] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Should be used in conjunction with at least
                          one other antituberculosis drug [AmFAR Tx Dir
                          1995;7(4)] [NIAID ACTG 135] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Drugs used with ethambutol have included
                          isoniazid, streptomycin, cycloserine,
                          ethionamide, pyrazinamide, viomycin, and
                          aminosalicylic acid [AmFAR Tx Dir 1995;7(4)]
                          [NIAID ACTG 135] [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Pulmonary tuberculosis [PDR 1995]
 SUBSTANCE INTERACTIONS   Concurrent administration of ethambutol with
                          other neurotoxic drugs, e.g., stavudine,
                          zalcitabine, etc., may increase the potential
                          for neurotoxicity such as optic and
                          peripheral neuritis. [USP DI 1995]
 ADVERSE EFFECTS          May produce decreases in visual acuity which
                          appear to be due to optic neuritis and to be
                          related to dose and duration of treatment.
                          Other adverse reactions include anaphylactoid
                          reactions, dermatitis pruritis, joint pain,
                          nausea, vomiting, gastrointestinal upset,
                          abdominal pain, fever, malaise, dizziness,
                          mental confusion, disorientation, possible
                          hallucinations, numbness, and tingling of the
                          extremities. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with known
                          hypersensitivity to ethambutol hydrochloride
                          and those with known optic neuritis unless
                          clinical judgement determines that it can be
                          used. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic, bacteriostatic
                          antituberculosis agent [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H24N2O2.2HCl [USAN
                          1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 277.24 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 198.5-200.3 C [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, DMSO; sparingly
                          soluble in ethanol; soluble with difficulty
                          in acetone, chloroform [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C58.78%, H11.84%,
                          N13.71%, O15.66% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 6.1 and 9.2 [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (100 and 400 mg). [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room temperature
                          15-30 C (59-86 F). [USP DI 1995]
 MANUFACTURERS            Lederle
 REFERENCES               Kemper CA, Havlir D, Haghighat D, Dube M,
                          Bartok AE, Sison JP, Yao Y, Yangco B, Leedom
                          JM, Tilles JG, et al. The individual
                          microbiologic effect of three
                          antimycobacterial agents, clofazimine,
                          ethambutol, and rifampin, on Mycobacterium
                          avium complex bacteremia in patients with
                          AIDS. J Infect Dis. 1994 Jul;170(1):157-64.
 REFERENCES               Shafran SD, Deschenes J, Miller M, Phillips
                          P, Toma E. Uveitis and pseudojaundice during
                          a regimen of clarithromycin, rifabutin, and
                          ethambutol. [letter]. N Engl J Med. 1994 Feb
                          10;330(6):438-9.
 REFERENCES               Benson CA. Treatment of disseminated disease
                          due to the Mycobacterium avium complex in
                          patients with AIDS. Clin Infect Dis. 1994
                          Apr;18 Suppl 3:S237-42.
 REFERENCES               Jacobson MA, Yajko D, Northfelt D, Charlebois
                          E, Gary D, Brosgart C, Sanders CA, Hadley WK.
                          Randomized, placebo-controlled trial of
                          rifampin, ethambutol, and ciprofloxacin for
                          AIDS patients with disseminated Mycobacterium
                          avium complex infection. J Infect Dis. 1993
                          Jul;168(1):112-9.
 REFERENCES               Jorup-Ronstrom C, Julander I, Petrini B.
                          Efficacy of triple drug regimen of amikacin,
                          ethambutol and rifabutin in AIDS patients
                          with symptomatic Mycobacterium avium complex
                          infection. J Infect. 1993 Jan;26(1):67-70.
 REFERENCES               Salomon N, Goldstein S, Perlman DC, Yancovitz
                          SR. Utility of an ofloxacin-containing
                          regimen in the management of hepatotoxicity
                          in HIV-infected persons with tuberculosis.
                          Int Conf AIDS. 1993 Jun 6-11;(1):342
                          (abstract no. PO-B07-1242).
 REFERENCES               Gatell JM. Tuberculosis (TBC) in HIV infected
                          patients (P): a multicentric, randomized
                          comparative study of a three versus a four
                          drug regimen. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B99 (abstract no. PoB 3077).
 REFERENCES               Kemper C, Havlir D, Haghighat D, Dube M,
                          Bartok A, Deresinski S. Effect of ethambutol,
                          rifampin, or clofazimine, given singly, on
                          Mycobacterium avium bacteremia in AIDS. Int
                          Conf AIDS. 1992 Jul 19-24;8(2):B101 (abstract
                          no. PoB 3087).
 REFERENCES               Kemper CA, Meng TC, Nussbaum J, Chiu J,
                          Feigal DF, Bartok AE, Leedom JM, Tilles JG,
                          Deresinski SC, McCutchan JA. Treatment of
                          Mycobacterium avium complex bacteremia in
                          AIDS with a four-drug oral regimen. Rifampin,
                          ethambutol, clofazimine, and ciprofloxacin.
                          Ann Intern Med. 1992 Mar 15;116(6):466-72.
 REFERENCES               Jorup-Rostrom C, Julander I, Petrini B.
                          Treatment of infections caused by
                          mycobacterium avium complex in 31 patients
                          with amikacin, ethambutol and rifabutin. Int
                          Conf AIDS. 1991 Jun 16-21;7(1):273 (abstract
                          no. M.B.2365).
 ENTRY MONTH              9104
 LAST REVISION DATE       960131
 

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