      Document 0214
 DOCN  DRG0214
 UNIQUE IDENTIFIER        DRG-0033
 NAME OF SUBSTANCE        Sulfadoxine [USAN 1995]
 REGISTRY NUMBER          2447-57-6
 STANDARD CHEMICAL NAME   4-Amino-N-(5,6-dimethoxy-4-pyrimidinyl)benzen-
                          esulfonamide [USAN 1995]
 SYNONYMS                 Sulforthomidine [Merck Index 1989]
 SYNONYMS                 Sulphormethoxine [Merck Index 1989]
 SYNONYMS                 Fanasil [USAN 1995]
 SYNONYMS                 Fanzil [USAN 1995]
 SYNONYMS                 N'-(5,6-Dimethoxy-4-pyrimidinyl)sulfanilamide
                          [Merck Index 1989]
 SYNONYMS                 6-(4-Aminobenzenesulfonamide)-4,5-dimethoxypy-
                          rimidine [Merck Index 1989]
 SYNONYMS                 4-Sulfanilamido-5,6-dimethoxypyrimidine
                          [Merck Index 1989]
 SYNONYMS                 Fansidar [USP DI 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 021
 SECONDARY SOURCE ID      Ro 4-4393 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Sulfadoxine competitively
                          inhibits dihydropteroate synthetase
                          preventing the incorporation of aminobenzoic
                          acid into dihydrofolic acid. Potentiation
                          occurs when sulfadoxine is combined with
                          pyrimethamine. The drugs are absorbed orally
                          and sulfadoxine is excreted mainly via the
                          kidneys with an apparent half-life of
                          elimination of 100 to 231 hours.
                          Pyrimethamine half-life ranges from 54 to 148
                          hours. Following a single oral dose
                          sulfadoxine peak plasma levels of 51 to 76
                          mcg/ml are reached in 2.5 to 6 hours.
                          Pyrimethamine peak levels of 0.13 to 0.4
                          mcg/ml are reached in 1.5 to 8 hours. Both
                          drugs are excreted in breast milk. [PDR 1995]
 DISEASES STUDIED/TREATED The combination of pyrimethamine and
                          sulfadoxine is used in the prophylaxis of
                          Pneumocystis carinii pneumonia (PCP) and
                          toxoplasmosis and in patients who cannot
                          tolerate co-trimoxazole prophylaxis [AHFS
                          Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1995]
 OTHER MAJOR USES         Treatment of Plasmodium falciparum malaria in
                          chloroquine-resistant patients (Fansidar)
                          [PDR 1995]
 SUBSTANCE INTERACTIONS   Caution should be observed when administering
                          sulfadoxine and pyrimethamine with bone
                          marrow depressants, hemolytics, hepatotoxic
                          drugs, folic acid antagonists and
                          antidiabetic agents. [USP DI 1995]
 ADVERSE EFFECTS          Adverse effects include all reactions
                          possible to sulfonamides. May cause fulminant
                          hepatic necrosis; may cause all major
                          reactions to sulfonamides, agranulocytosis,
                          aplastic anemia and other blood dyscrasias,
                          and reversible, mild leukopenia; possible
                          allergic, gastrointestinal, CNS, and
                          miscellaneous reactions. Fansidar: Severe
                          reactions include Stevens-Johnson syndrome
                          and toxic epidermal necrolysis; other effects
                          include, but are not limited to, diuresis and
                          hypoglycemia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated with patients with severe
                          renal insufficiency, marked liver parenchymal
                          damage or blood dyscrasias; hypersensitivity
                          to sulfonamides; or megaloblastic anemia due
                          to folate deficiency. Also contraindicated in
                          infants under 2 months of age and in pregnant
                          women at term and during nursing because
                          sulfonamides pass the placenta and are
                          excreted in the milk and may cause
                          kernicterus. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A structural analog of
                          aminobenzoic acid [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C12H14N4O4S [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 310.34 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C46.44%;
                          H4.55%; N18.05%; O20.62%; S10.33 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 190-194 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Very slightly soluble in water,
                          slightly soluble in alcohol and methanol
                          [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (Fansidar). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral (Fansidar). [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: (Fansidar) Store in tight
                          light-resistant container between 15-30 C
                          (59-86 F). [USP DI 1995]
 MANUFACTURERS            Hoffmann-La Roche
 REFERENCES               Hernandez JE, Flores LE, Estrada y Martin RM,
                          Mayorga R, Arathoon E. Toxoplasmic disease in
                          AIDS patients in Guatemala. Int Conf AIDS.
                          1994 Aug 7-12;10(2):156 (abstract no.
                          PB0636).
 REFERENCES               Ruf B, Schurmann D, Bergmann F, Schuler-Maue
                          W, Grunewald T, Gottschalk HS, Witt H, Pohle
                          HD. Efficacy of pyrimethamine/sulfadoxine in
                          the prevention of toxoplasmic encephalitis
                          relapses and Pneumocystis carinii pneumonia
                          in HIV-infected patients. Eur J Clin
                          Microbiol Infect Dis. 1993 May;12(5):325-9.
 REFERENCES               Grunewald T, Bergmann F, Eljaschewitsch J,
                          Pohle HD, Ruf B. Antiprotozoal prophylaxis in
                          AIDS patients--results of a prospective
                          randomized study comparing
                          Dapson/pyrimethamine and
                          sulfadoxine/pyrimethamine. Int Conf AIDS.
                          1993 Jun 6-11;9(1):56 (abstract no.
                          WS-B13-3).
 REFERENCES               Koppen S, Grunewald T, Jautzke G, Gottschalk
                          J, Pohle HD, Ruf B. Prevention of
                          Pneumocystis carinii pneumonia and
                          toxoplasmic encphalitis in human
                          imunodeficiency virus infected patients: a
                          clinical approach comparing aerosolized
                          pentamidine and pyrimethamine/sulfadoxine.
                          Clin Investig. 1992 Jun;70(6):508-12.
 REFERENCES               Partisani M, De Mautort E, Hassairi N, Divine
                          A, Fraisse P, Lang JM. Primary prophylaxis of
                          cerebral toxoplasmosis with
                          pyrimethamine-sulfadoxine in human
                          immunodeficiency virus-infected individuals
                          seropositive to Toxoplasma. Int Conf AIDS.
                          1992 Jul 19-24;8(2):B125 (abstract no. PoB
                          3230).
 REFERENCES               Eljaschewitsch J, Bergmann F, Grunewald T,
                          Ruf B. Monitoring of compliance in
                          HIV-positive patients treated with fansidar
                          for primary (PP) and secondary (SP)
                          prophylaxis of toxoplasmic encephalitis (TE)
                          using serum level determination. Int Conf
                          AIDS. 1992 Jul 19-24;8(2):B236 (abstract no.
                          PoB 3870).
 REFERENCES               Saint-Marc T, Livrozet JM, Moreau J, Garnier
                          JL, Sellem C, Touraine JL. Safety and
                          efficacy of pyrimethamine-sulfadoxine (P.S.)
                          in primary and secondary prophylaxis of
                          pneumocystosis (P.C.P.). Int Conf AIDS. 1991
                          Jun 16-21;7(2):242 (abstract no. W.B.2242).
 REFERENCES               Banhegyi D, Miskovits E, Szalvik J, Gerlei Z,
                          Ujhelyi E, Varnai F. Primary chemoprophylaxis
                          in AIDS. Int Conf AIDS. 1990 Jun
                          20-23;6(1):257 (abstract no. Th.B.541).
 REFERENCES               Paulic P, Pestre P, Bonnet E, Gasquet J,
                          Prodhome C, Gallais H. Treatment of brain
                          toxoplasmosis by Fansidar. Int Conf AIDs.
                          1990 Jun 20-23;6(10:241 (abstract no.
                          Th.B.478).
 REFERENCES               Hardy WD, Holzman RS, Avramis V, Bawdon R,
                          Fall H,  Feinberg J. Clinical and
                          pharmacokinetic interactions of combined
                          zidovudine (ZDV) therapy and
                          sulfadoxine-pyrimethamine (fansidar)
                          prophylaxis in post-PCP AIDS patients (ACTG
                          021). Int Conf AIDs. 1989 Jun 4-9;5294
                          (abstract no. T.B.P.46).
 ENTRY MONTH              8906
 LAST REVISION DATE       951110
 

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