      Document 0200
 DOCN  DRG0200
 UNIQUE IDENTIFIER        DRG-0047
 NAME OF SUBSTANCE        Doxorubicin [USAN 1996]
 REGISTRY NUMBER          23214-92-8
 RELATED REGISTRY NUMBER  25316-40-9
 STANDARD CHEMICAL NAME   10-((3-Amino-2,3,6-trideoxy-alpha-L-lyso-hexo-
                          pyranosyl)
                          oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-
                          8-(hydroxyacetyl)-1-methoxy-5,12-naphthacened-
                          ione [USAN 1996]
 SYNONYMS                 Adriblastina [USAN 1996]
 SYNONYMS                 Adriamycin [USAN 1996]
 SYNONYMS                 14-Hydroxydaunomycin [Merck Index 1989]
 SYNONYMS                 Adriacin [Merck Index 1989]
 SYNONYMS                 Rubex [USAN 1996]
 SYNONYMS                 Adriamycin PFS [USP DI 95]
 SYNONYMS                 Adriamycin RDF [USP DI 95]
 PROTOCOL ID NUMBERS      NIAID ACTG 006
 PROTOCOL ID NUMBERS      NIAID ACTG 008
 PROTOCOL ID NUMBERS      NIAID ACTG 074
 PROTOCOL ID NUMBERS      NIAID ACTG 075
 PROTOCOL ID NUMBERS      NIAID ACTG 094
 PROTOCOL ID NUMBERS      NIAID ACTG 142
 PROTOCOL ID NUMBERS      NCI 90 C-34
 PROTOCOL ID NUMBERS      NIAID ACTG 149
 PROTOCOL ID NUMBERS      FDA 121A
 PROTOCOL ID NUMBERS      FDA 134A
 PROTOCOL ID NUMBERS      NIAID ACTG 252
 PROTOCOL ID NUMBERS      NIAID ACTG 163
 IND NUMBER               IND 29,963
 SECONDARY SOURCE ID      NSC-123127 [USAN 1996]
 SECONDARY SOURCE ID      FI 106 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Doxorubicin appears to bind
                          by specific intercalation of the planar
                          anthracycline nucleus with the DNA double
                          helix and rapidly inhibits mitotic activity
                          and DNA and nucleic acid synthesis, effecting
                          mutagenesis and chromosomal aberrations; it
                          also binds to cell membranes and to plasma
                          proteins; pharmacokinetic studies show that
                          intravenous administration is followed by
                          rapid plasma clearance and significant tissue
                          binding; urinary excretion accounts for about
                          4-5 percent of the administered dose in 5
                          days; biliary excretion is the major
                          excretion route, with 40-50 percent being
                          recovered in the bile or feces in 7 days; it
                          does not cross the blood-brain barrier.
                          Although doxorubicin intercalates with DNA,
                          there is evidence that it can be actively
                          cytotoxic without entering cells by
                          interaction at the cell surface alone.
                          Half-life is biphasic for doxorubicin (0.6
                          and 16.7 hours) and its metabolites (3.3 and
                          31.7 hours). It exhibits extensive protein
                          tissue binding. It is cell cycle-specific for
                          the S phase of cell division. It is rapidly
                          (within 1 hour) metabolized to an active
                          metabolite, adriamycinol. Elimination is
                          mostly biliary (50 percent unchanged; 23
                          percent as adriamycinol). [PDR 1995] [USP DI
                          1995]
 DISEASES STUDIED/TREATED Treatment of Kaposi's sarcoma [AmFAR Tx Dir
                          1995;7(1)]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Used as single agent and combination
                          chemotherapy of acute leukemias, carcinomas,
                          lymphomas, sarcomas, tumors, and multiple
                          myeloma [PDR 1995]
 SUBSTANCE INTERACTIONS   Should not be mixed with heparin or
                          5-fluorouracil (may form a precipitate). May
                          potentiate toxicity of other anticancer
                          therapies. It may interact with allopurinol,
                          colchicine, probenecid, sulfinpyrazone, blood
                          dyscrasia-causing medications, other bone
                          marrow depressants, cyclophosphamide,
                          dactinomycin, mitomycin, daunorubicin,
                          hepatotoxic medications, streptozocin, killed
                          and live virus vaccines, and with radiation
                          therapy. [PDR 1995] [USP DI 1995]
 ADVERSE EFFECTS          May cause myelosuppression and
                          cardiotoxicity, reversible complete alopecia,
                          hyperpigmentation of nailbeds and dermal
                          creases, acute nausea and vomiting,
                          mucositis, phlebosclerosis, severe
                          cellulitis, anorexia, diarrhea, fever,
                          chills, urticaria, leukopenia, and
                          thrombopenia; anaphylaxis, conjunctivitis.
                          The urine may have a red color for 1-2 days
                          after administration. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients who have marked
                          myelosuppression induced by previous
                          treatment with other antitumor agents or by
                          radiotherapy. Doxorubicin is not recommended
                          for use by patients with cardiac problems; it
                          is contraindicated in patients who received
                          previous treatment with complete cumulative
                          doses of doxorubicin or daunorubicin. Should
                          not be used during pregnancy unless the
                          benefits to the patient outweigh the risks of
                          potential toxcicity to the fetus. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Cytotoxic anthracycline
                          antibiotic isolated from Streptomyces
                          Plucetius var. Caesius, consisting of a
                          naphthacenequinone nucleus linked through a
                          glycosidic bond at position 7 to the amino
                          sugar, daunosamine [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C27H29NO11 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 543.54 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C59.66%;
                          H5.38%; N2.57%; O32.38% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 229-231 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, methanol,
                          aqueous alcohols; practically insoluble in
                          acetone, benzene, chloroform, ethyl ether,
                          and petroleum ether [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Stability of doxorubicin
                          hydrochloride injectable solutions and
                          lyophilized powder for reconstitution varies
                          with the product's manufacturer. Generally,
                          solutions are stable at 2-8 C when protected
                          from light [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Reconstituted solutions for
                          injection are stable for 7 days at room
                          temperature [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Orange-red colored
                          crystals; aqueous solutions are yellow-orange
                          at acid pHs, orange-red at neutral pHs, and
                          violet-blue at pH greater than 9 [Merck Index
                          1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Both injectable solutions and
                          lyophilized powders for reconstitution are
                          available in various strengths in single and
                          multiple dose vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Injection; intravenous
                          infusion. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: The dry powders for reconstitution
                          should be stored at room temperature, 15 C to
                          30 C, and protected from light. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Reconstituted solutions should not
                          be kept beyond the recommended reconstitution
                          storage time which varies with the
                          manufacturer. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: All dosage forms should be protected
                          from light. [PDR 1995]
 MANUFACTURERS            Adria Laboratories
 REFERENCES               Gill PS, Miles SA, Mitsuyasu RT, Montgomery
                          T, McCarthy S, Espina BM, Feldstein M, Levine
                          AM. Phase I AIDS Clinical Trials Group (075)
                          study of adriamycin, bleomycin and
                          vincristine chemotherapy with zidovudine in
                          the treatment of AIDS-related Kaposi's
                          sarcoma. AIDS. 1994 Dec;8(12):1695-9.
 REFERENCES               Fischl MA, Krown SE, O'Boyle KP, Mitsuyasu R,
                          Miles S, Wernz JC, Volberding PA, Kahn J,
                          Groopman JE, Feinberg J, et al. Weekly
                          doxorubicin in the treatment of patients with
                          AIDS-related Kaposi's sarcoma. J Acquir
                          Immune Defic Syndr. 1993 Mar;6(3):259-64.
 REFERENCES               Sparano JA, Wiernik PH, Strack M, Leaf A,
                          Becker NH, Sarta C, Carney D, Elkind R, Shah
                          M, Valentine ES, et al. Infusional
                          cyclophosphamide, doxorubicin, and etoposide
                          in human immunodeficiency virus- and human
                          T-cell leukemia virus type I-related
                          non-Hodgkin's lymphoma: a highly active
                          regimen. Leuk Lymphoma. 1994
                          Jul;14(3-4):263-71.
 REFERENCES               Lionnet F, Pulik M, Tabah I. Four days
                          continuous infusion chemotherapy for AIDS
                          associated aggressive Kaposi sarcoma (KS). A
                          preliminary report. Int Conf AIDS. 1993 Jun
                          6-11;9(1):401 (abstract no. PO-B12-1597).
 REFERENCES               Mitsuyasu R, Gill P, Paredes J, Ambinder R,
                          Ratner L, Feldstein M. Preliminary results of
                          a phase I/II trial of combination
                          chemotherapy (ABV) with ddI or ddC in
                          AIDS-related Kaposi's sarcoma (ACTG 163). Int
                          Conf AIDS. 1993 Jun 6-11;9(1):396 (abstract
                          PO-B12-1565).
 REFERENCES               Schurmann D, Weiss R, Jautzke G, Pohle HD,
                          Ruf B. Intensive treatment of AIDS-related
                          non-Hodgkin's lymphomas with the MACOP-B
                          protocol. Int Conf AIDS. 1993 Jun
                          6-11;9(1):404 (abstract no. PO-B13-1616).
 REFERENCES               Ireland-Gill A, Espina BM, Akil B, Gill PS.
                          Treatment of acquired immunodeficiency
                          syndrome-related Kapos's sarcoma using
                          bleomycin-containing combination chemotherapy
                          regimens. Semin Oncol. 1992 Apr;19(2 Suppl
                          5):32-6; discussion 36-7.
 REFERENCES               Gill PS, Rarick M, McCutchan JA, Slater L,
                          Parker B, Muchmore E, Bernstein-Singer M,
                          Akil B, Espina BM, Krailo M, et al. Systemic
                          treatment of AIDS-related Kaposi's sarcoma:
                          results of a randomized trial. Am J Med. 1991
                          Apr;90(4):427-33.
 REFERENCES               Chavanet P, Bouyssou H, Solary E, Caillot D,
                          Grapin M, Gilles A, Waldner A, Portier H.
                          Advantages of vincristine (V), adriamycine
                          (A) and dexamethasone (D) (VAD) in a 4-day
                          infusion in the management of multiply
                          resistant Kaposi sarcoma (KS). Int Conf AIDS.
                          1991 Jun 16-21;7(2):274 (abstract no.
                          W.B.2371).
 REFERENCES               Levine AM, Wernz JC, Kaplan L, Rodman N,
                          Cohen P, Metroka C, Bennett JM, Rarick MU,
                          Walsh C, Kahn J, et al. Low-dose chemotherapy
                          with central nervous system prophylaxis and
                          zidovudine maintenance in AIDS-related
                          lymphoma. A prospective multi-institutional
                          trial. JAMA. 1991 Jul 3;266(1):84-8.
 ENTRY MONTH              8906
 LAST REVISION DATE       951128
 

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