      Document 0211
 DOCN  DRG0211
 UNIQUE IDENTIFIER        DRG-0036
 NAME OF SUBSTANCE        Dapsone [USAN 1995]
 REGISTRY NUMBER          80-08-0
 STANDARD CHEMICAL NAME   4,4'-Sulfonylbisbenzenamine [Merck Index
                          1989]
 SYNONYMS                 Avlosulphone [Merck Index 1989]
 SYNONYMS                 Croysulfone [Merck Index 1989]
 SYNONYMS                 DADPS [Merck Index 1989]
 SYNONYMS                 Diaphenylsulfone [Merck Index 1989]
 SYNONYMS                 Diphenasone [Merck Index 1989]
 SYNONYMS                 Diphone [Merck Index 1989]
 SYNONYMS                 Disulone [Merck Index 1989]
 SYNONYMS                 Dumitone [Merck Index 1989]
 SYNONYMS                 Eporal [Merck Index 1989]
 SYNONYMS                 Novophone [Merck Index 1989]
 SYNONYMS                 Sulphadione [Merck Index 1989]
 SYNONYMS                 Udolac [Merck Index 1989]
 SYNONYMS                 Bis(4-aminophenyl)sulfone [Merck Index 1989]
 SYNONYMS                 4,4'-Diaminodiphenyl sulfone [Merck Index
                          1989]
 SYNONYMS                 Acedapsone [CHEMLINE]
 SYNONYMS                 Araldite HT [CHEMLINE]
 SYNONYMS                 Croysulphone [Merck Index 1989]
 SYNONYMS                 Metabolite C [CHEMLINE]
 SYNONYMS                 Sulfanona-mae [Merck Index 1989]
 SYNONYMS                 Sulfonyldianiline [CHEMLINE]
 SYNONYMS                 Sumicure S [CHEMLINE]
 SYNONYMS                 Dapsone USP [PDR 1993]
 SYNONYMS                 DDS [Merck Index 1989]
 SYNONYMS                 4,4'-Sulfonyldianiline [Merck Index 1989]
 SYNONYMS                 Sulfona [CHEMLINE]
 SYNONYMS                 Diaminodiphenylsulfone [USP DI 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 081
 PROTOCOL ID NUMBERS      NIAID ACTG 108
 PROTOCOL ID NUMBERS      NIAID 88 CC-85
 PROTOCOL ID NUMBERS      NIAID 89 CC-02
 PROTOCOL ID NUMBERS      NIAID 89 CC-17
 PROTOCOL ID NUMBERS      FDA 07A
 PROTOCOL ID NUMBERS      FDA 07B
 PROTOCOL ID NUMBERS      NIAID ACTG 179
 PROTOCOL ID NUMBERS      NIAID CPCRA 013
 PROTOCOL ID NUMBERS      FDA 224A
 PROTOCOL ID NUMBERS      NIAID ACTG 277
 PROTOCOL ID NUMBERS      NIAID ACTG 283
 IND NUMBER               31,914
 IND NUMBER               32,622
 IND NUMBER               32,810
 SECONDARY SOURCE ID      1358F [Merck Index 1989]
 SECONDARY SOURCE ID      HSDB 5073 [CHEMLINE]
 SECONDARY SOURCE ID      HT 976 [CHEMLINE]
 SECONDARY SOURCE ID      NCI C01718 [CHEMLINE]
 SECONDARY SOURCE ID      NSC 6091D [CHEMLINE]
 SECONDARY SOURCE ID      WR 488 [CHEMLINE]
 SECONDARY SOURCE ID      NSC 6091 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Dapsone, a sulfone, is
                          bacteriostatic and probably acts by a
                          mechanism similar to that of the
                          sulfonamides. Both have a similar range of
                          antibacterial activity and are antagonized by
                          aminobenzoates (PABA). Dapsone may also act
                          as a dihydrofolate reductase inhibitor.
                          Dermatitis herpetiformis suppressant activity
                          not due to its bacteriostatic effect. When
                          given orally, Dapsone is rapidly and almost
                          completely absorbed, being detectable in the
                          blood a few minutes after ingestion, and
                          reaching blood peak levels in 4-8 hours.
                          Excretion of the drug is slow and a constant
                          blood level can be maintained with the usual
                          dosage. The half-life in plasma in different
                          individuals ranges from 10-50 hours (average
                          of 28 hours). Elimination is predominantly
                          renal (70-80 percent) as dapsone,
                          N-glucuronide, or N-sulfamate conjugates.
                          Dapsone is acetylated in the liver;
                          enterohepatic circulation accounts for
                          appreciable tissue levels 3 weeks after
                          therapy is terminated. [Drug Evaluations
                          Annual 1992] [PDR 1993] [USP DI 1989]
 DISEASES STUDIED/TREATED Pneumocystis carinii pneumonia (PCP),
                          treatment of mild PCP [AHFS Drug Information
                          1995]
 CLASSIFICATION CODE      Antibacterial [PDR 1995]
 CLASSIFICATION CODE      Dermatitis herpitiformis suppressant [PDR
                          1995]
 OTHER MAJOR USES         Treatment of Dermatitis herpetiformis [PDR
                          1989] Antibacterial drug for susceptible
                          cases of leprosy [PDR 1995]
 SUBSTANCE INTERACTIONS   Rifampin lowers dapsone levels 7-10 fold by
                          accelerating plasma clearance. Folic acid
                          antagonists such as pyrimethamine may
                          increase the likelihood of hematologic
                          reactions. Other potential drug interactions
                          include: aminobenzoates, bone marrow
                          depressants, and hemolytics. The antacid
                          buffer in dideoxyinosine (ddI) may inhibit
                          the gastric absorption of dapsone, which
                          requires acidity for dissolution.
                          Trimethoprim may increase plasma
                          concentration of both drugs and increase the
                          frequency and severity of dapsone's side
                          effects, especially methemoglobinemia and
                          hemolytic anemia. [USP DI 1995]
 ADVERSE EFFECTS          Hematologic Effects: Dose-related hemolysis
                          is the most common adverse effect and is seen
                          in patients with or without
                          glucose-6-phosphatase deficiency. Almost all
                          patients show a related decrease of
                          hemoglobin (1-2g), reticulocytosis (2-12
                          percent), shortened red cell life span, and
                          increased methemoglobin. May also cause
                          agranulocytosis, aplastic anemia and other
                          blood dyscrasias resulting in fatalities.
                          Nervous System Effects: Peripheral neuropathy
                          with motor loss is a definite but unusual
                          complication seen in non-leprosy patients.
                          Dapsone should be withdrawn if muscle
                          weakness appears. Recovery on withdrawal is
                          usually complete. Some patients have
                          tolerated retreatment at reduced dose. Body
                          As Whole: Additional adverse reactions
                          include: nausea, vomiting, abdominal pains,
                          vertigo, blurred vision, tinnitus, insomnia,
                          fever, headache, psychosis, phototoxicity,
                          tachycardia, albuminuria, nephrotic syndrome,
                          hypoalbuminemia without proteinuria, renal
                          papillary necrosis, male infertility,
                          drug-induced Lupus erythematosus and an
                          infectious mononucleosis-like syndrome. In
                          general these side effects regress off drug.
                          Serious cutaneous reactions may occur
                          including exfoliative dermatitis, toxic
                          erythema, erythema multiforme, toxic
                          epidermal necrolysis, morbilliform and
                          scarlatiniform reactions, and erythema
                          nodosum. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity to dapsone and/or its
                          derivatives. Should not be used by lactating
                          mothers since dapsone is excreted in
                          substantial amounts in breast milk; hemolytic
                          reactions can occur in neonates. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Aromatic amine sulfone
                          derivative [PDR 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C12H12N2O2S [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 248.31 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C58.04%,
                          H4.87%,  N11.28%, O12.89%, S12.91% [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 175-176 degrees C (also higher
                          melting form at 180.5 degrees C) [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in alcohol, methanol,
                          acetone, dilute HCl; practically insoluble in
                          water; insoluble in fixed and vegetable oils
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White odorless
                          crystalline powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Dapsone may discolor following
                          exposure to light. [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (25 mg and 100 mg). [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store in light-resistant containers
                          at controlled room temperature (59-86 F).
                          [PDR 1995]
 MANUFACTURERS            Jacobus Pharmaceuticals
 REFERENCES               Podzamczer D, Salazar A, Jimenez J, Consiglio
                          E, Santin M, Casanova A, Rufi G, Gudiol F.
                          Intermittent trimethoprim-sulfamethoxazole
                          compared with dapsone-pyrimethamine for the
                          simultaneous primary prophylaxis of
                          Pneumocystis pneumonia and toxoplasmosis in
                          patients infected with HIV. Ann Intern Med.
                          1995 May 15;122(10):755-61.
 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. NIAID AIDS
                          Clinical Trials Group. N Engl J Med. 1995 Mar
                          16;332(11):693-9.
 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. PB0629).
 REFERENCES               Opravil M, Heald A, Lazzarin A, Hirschel B,
                          Luthy R. Dapsone-pyrimethamine (DP) vs.
                          aerosolized pentamidine (AP) for combined
                          prophylaxis of PCP and toxoplasmic
                          encephalitis (TE). The Swiss Group for
                          Clinical Studies on AIDS. Int Conf AIDS. 1993
                          Jun 6-11;9(1):373 (abstract no. PO-B10-1429).
 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               Podzamczer D, Santin M, Jimenez J, Casanova
                          A, Bolao F, Gudiol GR. Thrice-weekly
                          cotrimoxazole than weekly
                          dapsone-pyrimethamine for the primary
                          prevention of Pneumocystis carinii pneumonia
                          in HIV-infected patients.  AIDS. 1993
                          Apr;7(4):501-6.
 REFERENCES               Mallolas J, Zamora L, Gatell JM, Miro JM,
                          Vernet E, Valls ME, Soriano E, SanMiguel JG.
                          Primary prophylaxis for Pneumocystis carinii
                          pneumonia: a randomized trial comparing
                          cotrimoxazole, aerosolized pentamidine and
                          dapsone plus pyrimethamine. AIDS. 1993
                          Jan;7(1):59-64.
 REFERENCES               Hewitt RG, Maliszewski M, Goldberg M, Harmon
                          B. Prevention of M. avium complex (MAC)
                          bacteremia in patients with CD4< 200 by
                          rifabutin, clarithromycin or dapsone. Int
                          Conf AIDS. 1993 Jun 6-11;9(1):333 (abstract
                          no. PO-B07-1184).
 REFERENCES               Torres RA, Barr M, Thorn M, Gregory G, Kiely
                          S, Chanin E, Carlo C, Martin M, Thornton J.
                          Randomized trial of dapsone and aerosolized
                          pentamidine for the prophylaxis of
                          Pneumocystis carinii pneumonia and
                          toxoplasmic encephalititis. Am J Med. 1993
                          Dec;95(6):573-83.
 REFERENCES               Torres RA, Barr M, Thorn M, Thornton J.
                          Pneumocystis prophylaxis failures: a
                          comparison of aerosolized pentamidine and
                          dapsone. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B140 (abstract no. PoB 3321).
 ENTRY MONTH              8906
 LAST REVISION DATE       951128
 

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