      Document 0216
 DOCN  DRG0216
 UNIQUE IDENTIFIER        DRG-0031
 NAME OF SUBSTANCE        Sulfamethoxazole [USAN 1995]
 REGISTRY NUMBER          723-46-6
 STANDARD CHEMICAL NAME   4-Amino-N-(5-methyl-3-isoxazolyl)benzenesulfo-
                          namide [USAN 1995]
 SYNONYMS                 Gantanol [USAN 1995]
 SYNONYMS                 Sulfisomezole [Merck Index 1989]
 SYNONYMS                 Sulfamethylisoxazole [Merck Index 1989]
 SYNONYMS                 Sulfamethoxizole [Merck Index 1989]
 SYNONYMS                 Sinomin [Merck Index 1989]
 SYNONYMS                 N1-(5-Methyl-3-isoxazolyl)sulfanilamide
                          [Merck Index 1989]
 SYNONYMS                 5-Methyl-3-sulfanilamidoisoxazole [Merck
                          Index 1989]
 SYNONYMS                 3-Sulfanilamido-5-methylisoxazole [Merck
                          Index 1989]
 SYNONYMS                 3(p-Aminophenylsulfonamido)-5-methylisoxazole
                          [Merck Index 1989]
 SYNONYMS                 Eusaprim [Merck Index 1989]
 SYNONYMS                 Gantaprim [Merck Index 1989]
 SYNONYMS                 Gantrim [Merck Index 1989]
 SYNONYMS                 Bactrim [Merck Index 1989]
 SYNONYMS                 Baktar [Merck Index 1989]
 SYNONYMS                 Co-trimoxazole [USAN 1995]
 SYNONYMS                 Abacin [Merck Index 1989]
 SYNONYMS                 Drylin [Merck Index 1989]
 SYNONYMS                 Kepinol [Merck Index 1989]
 SYNONYMS                 Momentol [Merck Index 1989]
 SYNONYMS                 Nopil [Merck Index 1989]
 SYNONYMS                 Omsat [Merck Index 1989]
 SYNONYMS                 Septra [Merck Index 1989]
 SYNONYMS                 Septrim [Merck Index 1989]
 SYNONYMS                 Sigaprim [Merck Index 1989]
 SYNONYMS                 Sulfotrim [Merck Index 1989]
 SYNONYMS                 Sulfotrimin [Merck Index 1989]
 SYNONYMS                 Sulprim [Merck Index 1989]
 SYNONYMS                 Sumetrolim [Merck Index 1989]
 SYNONYMS                 Suprim [Merck Index 1989]
 SYNONYMS                 Tacumil [Merck Index 1989]
 SYNONYMS                 Teleprim [Merck Index 1989]
 SYNONYMS                 TMS 480 [Merck Index 1989]
 SYNONYMS                 Trigonyl [Merck Index 1989]
 SYNONYMS                 Linaris [Merck Index 1989]
 SYNONYMS                 Eltrianyl [Merck Index 1989]
 SYNONYMS                 Microtrim [Merck Index 1989]
 SYNONYMS                 Trimesulf [Merck Index 1989]
 SYNONYMS                 Apo-sulfatrim [Merck Index 1989]
 SYNONYMS                 Fectrim [Merck Index 1989]
 SYNONYMS                 Trimforte [Merck Index 1989]
 SYNONYMS                 Uro-septra [Merck Index 1989]
 SYNONYMS                 Comox [Merck Index 1989]
 SYNONYMS                 Cotrim-Puren [Merck Index 1989]
 SYNONYMS                 Duratrimet [Merck Index 1989]
 SYNONYMS                 Helveprim [Merck Index 1989]
 SYNONYMS                 Imexim [Merck Index 1989]
 SYNONYMS                 Laratrim [Merck Index 1989]
 SYNONYMS                 Supracombin [Merck Index 1989]
 SYNONYMS                 Thiocuran [Merck Index 1989]
 SYNONYMS                 Uroplus [Merck Index 1989]
 SYNONYMS                 Bactramin [Merck Index 1989]
 SYNONYMS                 Bactromin [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 021
 PROTOCOL ID NUMBERS      NIAID ACTG 029
 PROTOCOL ID NUMBERS      NIAID ACTG 030
 PROTOCOL ID NUMBERS      NIAID ACTG 031
 PROTOCOL ID NUMBERS      NIAID ACTG 033
 PROTOCOL ID NUMBERS      NIAID ACTG 037
 PROTOCOL ID NUMBERS      NIAID ACTG 040
 PROTOCOL ID NUMBERS      NIAID ACTG 081
 PROTOCOL ID NUMBERS      NIAID ACTG 108
 PROTOCOL ID NUMBERS      NIAID ACTG 167
 PROTOCOL ID NUMBERS      FDA 007A
 PROTOCOL ID NUMBERS      FDA 056A
 PROTOCOL ID NUMBERS      NIAID CPCRA 006
 PROTOCOL ID NUMBERS      NIAID 93 I-36
 PROTOCOL ID NUMBERS      FDA 224A
 PROTOCOL ID NUMBERS      NIAID ACTG 268
 PROTOCOL ID NUMBERS      NIAID ACTG 283
 SECONDARY SOURCE ID      RO 4-2130 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Rapidly and completely
                          absorbed following oral administration, with
                          peak plasma level occurring 2-4 hours
                          thereafter. Approximately 70 percent is
                          plasma protein bound, with 80-90 percent of
                          the unbound portion in the nonacetylated
                          form. The half-life of sulfamethoxazole (SMX)
                          after oral administration (1 gm) is
                          approximately 10 hours (considerably greater
                          in patients with severely impaired renal
                          function), with excretion primarily by the
                          kidneys through glomerular filtration and
                          tubular secretion. Urine levels of the drug
                          are considerably higher than serum levels. A
                          total of 80-100 percent of the dose is
                          excreted in the urine as total SMX, of which
                          30 percent is intact drug and the remainder
                          is its predominant metabolite, a
                          N4-acetylated derivative. [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved Bactrim and Septra 6/23/81 for
                          PCP treatment and approved 1/7/94 for PCP
                          prophylaxis [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Used in formulation with trimethoprim for
                          treatment of Pneumocystis carinii pneumonia
                          in AIDS patients [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1995]
 OTHER MAJOR USES         Inclusion conjunctivitis; malaria due to
                          chloroquine-resistant strains of Plasmodium
                          falciparum when used as an adjunctive
                          therapy; acute otitis media due to
                          Haemophilus influenzae when used
                          concomitantly with adequate doses of
                          penicillin; nocardiosis; toxoplasmosis as
                          adjunctive therapy with pyrimethamine;
                          trachoma; and urinary tract infections [PDR
                          1995]
 SUBSTANCE INTERACTIONS   May produce an increased incidence of
                          thrombopenia with purpura in elderly
                          concurrently receiving certain diuretics
                          (primarily, thiazides), may prolong
                          prothrombin time in patients receiving
                          warfarin anticoagulant, may inhibit the
                          hepatic metabolism of phenytoin, and may
                          displace methotrexate from plasma protein
                          binding sites thus increasing free
                          methotrexate concentrations. Concurrent
                          administration of sulfamethoxazole and
                          trimethoprim does not affect the excretion
                          pattern of either drug. [PDR 1995]
 ADVERSE EFFECTS          Similarities among the sulfonamides require
                          that these adverse reactions be considered
                          applicable for all derivatives:
                          agranulocytosis, aplastic anemia,
                          thrombocytopenia, leukopenia, hemolytic
                          anemia, purpura, hypoprothrombinemia,
                          methemoglobinemia, neutropenia, and
                          eosinophilia. Anaphylaxis, allergic
                          myocarditis, serum sickness, conjunctival and
                          scleral injection, generalized allergic
                          reactions. In addition, periarteritis nodosa
                          and systemic lupus erythematosus have been
                          reported. Stevens-Johnson syndrome, epidermal
                          necrolysis, erythema multiforme, exfoliative
                          dermatitis, photosensitivity, pruritis,
                          urticaria, rash, and generalized skin
                          eruptions. Hepatitis, hepatocellular
                          necrosis, pseudomembranous enterocolitis,
                          pancreatitis, stomatitis, glossitis, nausea,
                          emesis, abdominal pain, diarrhea, and
                          anorexia. Creatinine elevation, toxic
                          nephrosis with oliguria and anuria. The
                          frequency of renal complications is
                          considerably lower in patients receiving the
                          more soluble sulfonamides. Convulsions,
                          peripheral neuritis, ataxia, vertigo,
                          tinnitus, headache, hallucinations,
                          depression, and apathy. The sulfonamides bear
                          certain chemical similarities to some
                          goitrogens, diuretics (acetazolamide and the
                          thiazides) and oral hypoglycemic agents.
                          Cross-sensitivity may exist with these
                          agents. Diuresis and hypoglycemia have
                          occurred rarely in patients receiving
                          sulfonamides. Arthraglia, myalgia, pulmonary
                          infiltrates, and, rarely, edema (including
                          periorbital), pyrexia, chills, weakness,
                          fatigue, and insomnia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with allergies to
                          sulfonamides, furosemide, thiazides
                          diuretics, sulfonylureas, or carbonic
                          anhydrase inhibitors. Avoid use in patients
                          with the following: blood dyscrasias,
                          megaloblastic anemias due to folate
                          deficiency, in hepatic function impairment,
                          porphyria and renal function impairment. [USP
                          DI 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Sulfonamide (derivative)
                          [Drug Evaluations Annual 1992]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H11N3O3S [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 253.28 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C47.42%;
                          H4.38%; N16.60%; O18.95%; S12.66% [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Practically insoluble in water,
                          ether, and chloroform; freely soluble in
                          acetone and dilute solutions of NaOH;
                          sparingly soluble in alcohol [USP DI 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Almost white, odorless,
                          tasteless solid [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 167 C [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets containing 0.5 Gm
                          sulfamethoxazole; suspension, 10%, containing
                          0.5% Gm sulfamethoxazole per teaspoonful (5
                          ml). [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Intravenous combination products
                          containing 16 mg/ml trimethoprim and 80 mg/ml
                          sulfamethoxazole. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Oral suspensions containing 40
                          mg/5 ml trimethoprim and 200 mg/5 ml
                          sulfamethoxazole. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous (combined
                          with trimethoprim) [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Tablets and suspensions should be
                          stored at 15-25 C (59-68 F) in a tight
                          light-resistant container; protect
                          suspensions from freezing. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Intravenous preparations should be
                          stored at 15 C to 25 C and should not be
                          refrigerated. [PDR 1995]
 MANUFACTURERS            Hoffman-La Roche
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Bozzette SA, Finkelstein DM, Spector SA,
                          Frame P, Powderly WG, He W, Phillips L,
                          Craven D, van der Horst C, Feinberg J. A
                          randomized trial of three antipneumocystis
                          agents in patients with advanced human
                          immunodeficiency virus infection. N Engl J
                          Med. 1995 Mar 16;332(11): 693-9.
 REFERENCES               Montgomery AB, Feigal DW Jr, Sattler F, Mason
                          GR, Catanzaro A, Edison R, Markowitz N,
                          Johnson E, Ogawa S, Rovzar M, et al.
                          Pentamidine aerosol versus
                          trimethoprim-sulfamethoxazole for
                          Pneumocystis carinii in acquired immune
                          deficiency syndrome. Am J Respir Crit Care
                          Med. 1995 Apr;151(4):1068-74.
 REFERENCES               Saah AJ, Hoover DR, Peng Y, Phair JP,
                          Visscher B, Kingsley LA, Schrager LK.
                          Predictors for failure of Pneumocystis
                          carinii pneumonia prophylaxis. JAMA. 1995 Apr
                          19;273(15):L1197-202.
 REFERENCES               Bozzette SA, Forthal D, Sattler FR, Kemper C,
                          Richman DD, Tilles JG, Leedom J, McCutchan
                          JA. The tolerance for zidovudine plus thrice
                          weekly or daily trimethoprim-sulfamethoxazole
                          with and without leucovorin for primary
                          prophylaxis in advanced HIV disease. Am J Md.
                          1995 Feb;98(2):177-82.
 REFERENCES               May T, Beuscart C, Reynes J, Marchou B,
                          Leclercq P,  Borsa Lebas F, Saba J, Micoud M,
                          Mounton Y, Canton P.
                          Trimethoprim-sulfamethoxazole versus
                          aerosolized pentamidine for primary
                          prophylaxis of Pneumocystis carinii
                          pneumonia: a prospective, randomized,
                          controlled clinical trial. J Acquir Immune
                          Defic Syndr. 1994 May;7(5):457-62.
 REFERENCES               Lee BL, Delahunty T, Safrin S. The
                          hydroxylamine of sulfamethoxazole and adverse
                          reactions in patients with acquired
                          immunodeficiency syndrome. Clin Pharmacol
                          Ther. 1994 Aug;56(2):184-9.
 REFERENCES               Hughes W, Leoung G, Kramer F, Bozzette SA,
                          Safrin S, Frame P, Clumeck N, Masur H,
                          Lancaster D, Chan C, et al. Comparison of
                          atovaquone (566C80) with
                          trimethoprim-sulfamethoxazole to treat
                          Pneumocystis carinii pneumonia in patients
                          with AIDS. N Engl J Med. 1993 May
                          27;328(21):1521-7.
 REFERENCES               Mallolas J, Zamora L, Gatell J, Miro JM,
                          Vernet E, Valls ME, Soriano E, SanMiguel JG.
                          Primary prophylaxis for Pneumocystis carrinii
                          pneumonia: a randomized trial comparing
                          cotrimoxazole, aerosolized pentamidine and
                          dapsone plus pyrimethamine. AIDS. 1993
                          Jan;7(1):59-64.
 REFERENCES               Tournerie C, Charreau I. Cotrimoxazole
                          (TMP-SMX) for primary prophylaxis of
                          Toxoplasma encephalitis in advanced HIV
                          patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):56 (abstract no. WS-B13-2).
 REFERENCES               Reynes J, Brunschwig C, Atoui N, Fabre J,
                          Siffert M, Janbon F. Foate deficiency and
                          cotrimoxazole prophylaxis during HIV
                          infection. Int Conf AIDS. 1993 Jun
                          6-11;9(1):387 (abstract no. PO-B10-1512).
 ENTRY MONTH              8906
 LAST REVISION DATE       960612
 

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