      Document 0112
 DOCN  DRG0112
 UNIQUE IDENTIFIER        DRG-0135
 NAME OF SUBSTANCE        Dacarbazine [USAN 1996]
 REGISTRY NUMBER          4342-03-4
 STANDARD CHEMICAL NAME   5-(3,3-dimethyl-1-triazeno)-imidazole-4-carbo-
                          xamide [USAN 1996]
 SYNONYMS                 DTIC [USAN 1996]
 SYNONYMS                 DTIC-Dome [PDR 1995]
 SYNONYMS                 5(or 4)-(dimethyltriazeno)imidazole-4(or
                          5)-carboxamide [Merck Index 1989]
 SYNONYMS                 DIC [Merck Index 1989]
 SYNONYMS                 Dacatic [Merck Index 1989]
 SYNONYMS                 Deticene [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 149
 SECONDARY SOURCE ID      NSC-45388 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Dacarbazine is thought to be
                          an alkylating agent, but other mechanisms of
                          action are possible. Although the exact
                          mechanism is unkown three hypotheses have
                          been offered: (1) inhibition of DNA sythesis
                          by acting as a purine analog (2) action as an
                          alkylating agent (3) interactions with SH
                          groups. After intravenous administration,
                          volume of distribution exceeds total body
                          water content, suggesting localization in
                          some body tissue, probably the liver.
                          Disappearance from plasma is biphasic with
                          initial half-life of 19 minutes and terminal
                          half-life of 5 hours. Dacarbazine is subject
                          to renal tubular secretion rather than
                          glomerular filtration. At therapeutic
                          concentrations, dacarbazine is not
                          appreciably bound to human plasma protein. It
                          crosses the blood-brain barrier to only a
                          limited extent. The drug is extensively
                          degraded in humans. [PDR 1995] [USP DI 1995]
 DISEASES STUDIED/TREATED Treatment of Hodgkin's disease in
                          HIV-infected patients [AmFAR Tx Dir
                          1995;7(4)] [NIAID ACTG 149]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Treatment of metastatic malignant melanoma
                          and for Hodgkin's disease as a second-line
                          therapy when used in combination with other
                          effective agents [PDR 1995]
 SUBSTANCE INTERACTIONS   May interact with allopurinol, blood
                          dyscrasia-causing medications, bone marrow
                          depressants or radiation therapy, hepatic
                          enzyme inducers, killed-virus vaccines, or
                          live-virus vaccines. [USP DI 1995]
 ADVERSE EFFECTS          The most common adverse effect is hemopoietic
                          depression; other reported adverse effects
                          include hepatic toxicity accompanied by
                          hepatic vein thrombosis and hepatocellular
                          necrosis, and anaphylaxis. Symptoms of
                          anorexia, nausea, and vomiting are the most
                          frequently noted of all toxic reactions
                          (90%). Also noted, but more rare, are
                          flu-like symptoms, myalgias, malaise,
                          alopecia, facial flushing, and facial
                          paresthesia. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with demonstrated
                          hypersensitivity to dacarbazine. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The synthetic analog of the
                          naturally occurring purine precursor
                          5-amino-1H-imidazole-4-carboxamide [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Colorless to ivory
                          colored solid [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C6H10N6O [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 182.19 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C39.55% H5.53% N46.13%
                          O8.78% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Slightly soluble in water and in
                          alcohol [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Reconstituted solutions are stable
                          for up to 72 hours at 4 C (39 F) or for up to
                          8 hours at 20 C (68 F). Incompatible with
                          solutions of hydrocortisone sodium succinate
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 4.42 [AHFS DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 100 or 200 mg vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 2-8 C (36-46 F). Light
                          sensitive. [PDR 1995]
 REFERENCES               Tirelli U, Errante D, Dolcetti R, Gloghini A,
                          Serraino D, Vaccher E, Franceschi S, Boiocchi
                          M, Carbone A. Hodgkin's disease and human
                          immunodeficiency virus infection:
                          clinicopathologic and virologic features of
                          114 patients from the Italian Cooperative
                          Group on AIDS and Tumors. J Clin Oncol. 1995
                          Jul;13(7):1758-67.
 REFERENCES               Levy R, Colonna P, Tourani JM, Gastaut JA,
                          Brice P, Raphael M, Taillan B, Andrieu JM.
                          Human immunodeficiency virus associated
                          Hodgkin's disease: report of 45 cases from
                          the French Registry of HIV-Associated Tumors.
                          Leuk Lymphoma. 1995 Feb;16(5-6):451-6.
 REFERENCES               Muhonen T, Hahka-Kemppinen M, Pakkala S,
                          Pyrhonen S. Decreasing CD4/CD8 ratio during
                          prolonged four-drug chemotherapy plus
                          interferon treatment for metastatic melanoma.
                          J Immunother. 1994 Jan;15(1):67-73.
 REFERENCES               Novati S, Malfitano A, Sacchi P, Patruno SF,
                          Tornari PM, Rondanelli EG. HIV-related
                          Hodgkin's disease. Report of nine cases.
                          Haematologica. 1993 Jan-Feb;78(1):34-7.
 REFERENCES               Errante D, Tirelli U, Milo D, Rizzardini G,
                          Nasti G, Chieppa F. Chemotherapy (CT) with
                          and without zidovudine (AZT) for Hodgkin's
                          disease (HD) and HIV infection: a comparison
                          in 49 patients (PTS). Int Conf AIDS. 1993 Jun
                          6-11;9(1):404 (abstract no. PO-B13-1611).
 REFERENCES               Bouabdallah R, Quiles N, Bonnet E, Petit N,
                          et al. Hodgkin's disease (HD) in HIV infected
                          patients: clinical, histologic and
                          therapeutic aspects. Int Conf AIDS 1993 Jun
                          6-11;9(1):405 (abstract no. PO-B13-1617).
 REFERENCES               Vaccher E, Tirelli U, Milo D Chieppa F,
                          Alberici F, Branz F, Ambrosini G, Giudici M,
                          Lazzarin A, Cargnel A, et al. Hodgkin's
                          disease and HIV infection (HD-HIV): a report
                          of 92 patients from the GICAT (Italian
                          Cooperative Group on AIDS and Tumors), with
                          emphasis on prospective study with combined
                          chemotherapy and zidovudine (AZT) in 16
                          patients. Int Conf AIDS. 1992 Jul
                          19-24;8(1):Mo16 (abstract no. MoB 0059).
 REFERENCES               Tirelli U, Errante D, Vaccher E, Spina M,
                          Gastaldi R, Rizzardini G, Mandelli F, Milo D,
                          Nosari AM, Rossi G, et al. HODGKIN'S DISEASE
                          AND HIV INFECTION (HD-HIV): A REPORT OF 92
                          PATIENTS FROM THE GICAT (ITALIAN COOPERATIVE
                          GROUP ON AIDS AND TUMORS), WITH EMPHASIS ON
                          PROSPECTIVE STUDY WITH COMBINED CHEMOTHERAPY
                          (CT) AND ZIDOVUDINE (AZT) IN 16 PATIENTS
                          (MEETING ABSTRACT) Proc Annu Meet Am Soc Clin
                          Oncol; 11:A2 1992.
 REFERENCES               Monfardini S, Tirelli U, Vaccher E, Fo:a R,
                          Gavosto F. Hodgkin's disease in 63
                          intravenous drug users infected with human
                          immunodeficiency virus. Gruppo Italiano
                          Cooperativo AIDS & Tumori (GICAT). Ann Oncol.
                          1991 Feb;2 Suppl 2:201-5.
 REFERENCES               Sloand E, Kumar P, Pierce P. Treatment of
                          pulmonary Kaposi's sarcoma (PKS) with
                          combination chemotherapy. Int Conf AIDS. 1991
                          Jun 16-21;7(1):226 (abstract no. M.B.2178).
 ENTRY MONTH              9201
 LAST REVISION DATE       960111
 

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