      Document 0033
 DOCN  DRG0033
 UNIQUE IDENTIFIER        DRG-0214
 NAME OF SUBSTANCE        Sulfadiazine [USAN 1996]
 REGISTRY NUMBER          68-35-9
 STANDARD CHEMICAL NAME   Benzenesulfonamide, 4-amino-N-2-pyrimidinyl-
                          [USAN 1996]
 SYNONYMS                 Adiazine [Merck Index 1989]
 SYNONYMS                 Debenal [Merck Index 1989]
 SYNONYMS                 Delvoprim [Merck Index 1989]
 SYNONYMS                 Diazyl [Merck Index 1989]
 SYNONYMS                 Eskadiazine [USAN 1996]
 SYNONYMS                 Pyrimal [Merck Index 1989]
 SYNONYMS                 Sterazine [Merck Index 1989]
 SYNONYMS                 Sulfolex [Merck Index 1989]
 SYNONYMS                 Ultradiazin [Merck Index 1989]
 SYNONYMS                 Sulphadiazine [USAN 1996]
 SYNONYMS                 Coco-Diazine [USAN 1996]
 SYNONYMS                 Cremodiazine [CHEMLINE]
 SYNONYMS                 Deltazine [CHEMLINE]
 SYNONYMS                 Diazolone [CHEMLINE]
 SYNONYMS                 Diazovit [CHEMLINE]
 SYNONYMS                 Honey Diazine [CHEMLINE]
 SYNONYMS                 Lipo-Diazine [CHEMLINE]
 SYNONYMS                 Lipo-Levazine [CHEMLINE]
 SYNONYMS                 Liquadiazine  [CHEMLINE]
 SYNONYMS                 Microsulfon [CHEMLINE]
 SYNONYMS                 Neazine [CHEMLINE]
 SYNONYMS                 N1-2-Pyrimidinylsulfanilamide [CHEMLINE]
 SYNONYMS                 Piridisir [CHEMLINE]
 SYNONYMS                 Sanodiazine [CHEMLINE]
 SYNONYMS                 SDA [CHEMLINE]
 SYNONYMS                 Solfadiazina [CHEMLINE]
 SYNONYMS                 Sulfacombin [CHEMLINE]
 SYNONYMS                 Spofadrizine [CHEMLINE]
 SYNONYMS                 Sulfadiazina [CHEMLINE]
 SYNONYMS                 Sulfapyrimidine [Merck Index 1989]
 SYNONYMS                 Theradiazine [CHEMLINE]
 PROTOCOL ID NUMBERS      NIAID ACTG 237
 SECONDARY SOURCE ID      AI3-01047 [CHEMLINE]
 SECONDARY SOURCE ID      RP 2616 [CHEMLINE]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Competitively inhibits
                          bacterial synthesis of folic acid from
                          aminobenzoic acid by inhibiting
                          dihydropteroate synthetase. Bacterioststic
                          effect in those bacteria which must
                          synthesize folic acid. Readily absorbed from
                          the gastrointestinal tract. After a single 2
                          g oral dose, a peak of 6.04 mg/100 ml is
                          reached in 4 h; of this, 4.675 mg/100 ml is
                          free drug. Sulfadiazine diffuses into the
                          CSF; free drug reaches 32 to 65% of blood
                          levels and total drug is 40 to 60%. The drug
                          is excreted mainly in the urine at
                          concentrations 10 to 25 times greater than
                          serum levels. About 10% of a single oral dose
                          is excreted in 6 h, 50% within 24 h and 60 to
                          85% in 48 to 72 h. [PDR 1995] [AHFS Drug
                          Information 1995]
 DISEASES STUDIED/TREATED Toxoplasmic encephalitis [NIAID ACTG 237]
                          [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Gram positive and gram negative infections,
                          excluding urinary tract infections, unless
                          other sulfonamides have failed;
                          toxoplasmosis; as an adjunct to pyrimethamine
                          therapy; malaria; trachoma; nocardiosis and
                          chancroid [PDR 1995]
 SUBSTANCE INTERACTIONS   The effects of oral anticoagulants (coumarin
                          or indandione derivatives) and methotrexate
                          may be increased by sulfadiazine.
                          Sulfonylurea hypoglycemic agents, thiazide
                          diuretics and uricosuric agents may be
                          potentiated. Agents such as indomethacin,
                          probenecid, and salicylates may displace the
                          sulfa from plasma albumin and increase the
                          concentrations of free drug in the plasma.
                          Interactions have also been reported with
                          hemolytics, hepatotoxic medications and
                          methenamine. [PDR 1995] [USP DI 1995]
 ADVERSE EFFECTS          Adverse effects include crystalluria
                          (crystals in the urine), hematuria, kidney
                          stones, kidney failure, hypersensitivity
                          reactions, and anemia. [NIAID ACTG 237] [PDR
                          1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity to sulfonamides, in infants
                          less than 2 months of age, and in pregnant
                          women at term and during nursing. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Dihydrofolate synthetase
                          inhibitor; a synthetic derivative of
                          p-amino-benzenesulfonamide [NIAID ACTG 237]
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H10N4O2S [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 250.28 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 252-256 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMP: C47.99%, H4.03%, N22.39%,
                          O12.79%, S12.81% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Sparingly soluble in water at 37
                          C and in alcohol or acetone. Soluble at 1
                          g/620 ml human serum at 37 C. Freely soluble
                          in dilute mineral acids and in solutions of
                          potassium and sodium hydroxides and in
                          ammonia water [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Stable in air but slowly darkens
                          on exposure to light [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: A white or slightly
                          yellow, odorless or nearly odorless powder
                          [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 500 mg tablets. [NIAID ACTG 237]
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID ACTG 237] [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 15-30 C. Protect from
                          light. [NIAID ACTG 237] [PDR 1995]
 MANUFACTURERS            EON Labs Manufacturing
 REFERENCES               Caumes E, Bocquet H, Guermonprez G, Rogeaux
                          O, Bricaire F, Katlama C, Gentilini M.
                          Adverse cutaneous reactions to
                          pyrimethamine/sulfadiazine and
                          pyrimethamine/clindamycin in patients with
                          AIDS and toxoplasmic encephalitis. Clin
                          Infect Dis. 1995 Sep;21(3):656-8.
 REFERENCES               Podzamczer D, Miro JM, Bolao F, Gatell JM,
                          Cosin J, Sirera G, Domingo P, Laguna F,
                          Santamaria J, Verdejo J. Twice-weekly
                          maintenance therapy with
                          sulfadiazine-pyrimethamine to prevent
                          recurrent toxoplasmic encephalitis in
                          patients with AIDS. Spanish Toxoplasmosis
                          Study Group [see comments]. Ann Intern Med.
                          1995 Aug 1;123(3):175-80.
 REFERENCES               Winstanley P. Drug treatment of toxoplasmic
                          encephalitis in acquired immunodeficiency
                          syndrome. Postgrad Med J. 1995
                          Jul;71(837):404-8.
 REFERENCES               Laissy JP, Soyer P, Parlier C, Lariven S,
                          Benmelha Z, Servois V, Casalino E, Bouvet E,
                          Sibert A, Vachon F, et al. Persistent
                          enhancement after treatment for cerebral
                          toxoplasmosis in patients with AIDS:
                          predictive value for subsequent recurrence.
                          AJNR Am J Neuroradiol. 1994 Oct;15(9):1773-8.
 REFERENCES               Gregoire NE. Prevention of cerebral
                          toxoplasmosis in severely depressed patients
                          with AIDS. Int Conf AIDS. 1994 Aug
                          7-12;10(2):154 (abstract no. PBO629).
 REFERENCES               Saba J, Morlat P, Raffi F, Hazebroucq V, Joly
                          V, Leport C, Vilde JL. Pyrimethamine plus
                          azithromycin for treatment of acute
                          toxoplasmic encephalitis in patients with
                          AIDS. Eur J Clin Microbiol Infect Dis. 1993
                          Nov;12(11):853-6.
 REFERENCES               McCabe R, Chirurgi V. Issues in
                          toxoplasmosis. Infect Dis Clin North Am. 1993
                          Sep;7(3):587-604.
 REFERENCES               Hein R, Brunkhorst R, Thon WF, Schedel I,
                          Schmidt RE. Symptomatic sulfadiazine
                          crystalluria in AIDS patients: a report of
                          two cases. Clin Nephrol. 1993
                          May;39(5):254-6.
 REFERENCES               Farinas MC, Echevarria S, Sampedro I,
                          Gonzalez A, Perez del Molino A,
                          Gonzalez-Macias J. Renal failure due to
                          sulphadiazine in AIDS patients with cerebral
                          toxoplasmosis. J Intern Med. 1993
                          Apr;233(4):365-7.
 REFERENCES               Dannemann B, McCutchan JA, Israelski D,
                          Antoniskis D, Leport C, Luft B, Nussbaum J,
                          Clumeck N, Morlat P, Chiu J, et al. Treatment
                          of toxoplasmic encephalitis in patients with
                          AIDS. A randomized trial comparing
                          pyrimethamine plus clindamycin to
                          pyrimethamine plus sulfadiazine. Ann Intern
                          Med. 1992 Jan 1;116(1):33-43.
 ENTRY MONTH              9408
 LAST REVISION DATE       960503
 

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