      Document 0235
 DOCN  DRG0235
 UNIQUE IDENTIFIER        DRG-0012
 NAME OF SUBSTANCE        Sargramostim [USAN 1995]
 REGISTRY NUMBER          123774-72-1
 STANDARD CHEMICAL NAME   Colony-stimulating factor 2 (human clone
                          pHG25 protein moiety), 23-L-leucine- [USAN
                          1995]
 SYNONYMS                 GM-CSF [AMFAR Tx Dir Jan 1995;7(4)]
 SYNONYMS                 CSF-GM [MeSH]
 SYNONYMS                 Histamine-Producing Cell-Stimulating Factor
                          [MeSH]
 SYNONYMS                 TC-GM-CSF [MeSH]
 SYNONYMS                 CSF-2 [MeSH]
 SYNONYMS                 GM-CSF [MeSH]
 SYNONYMS                 Granulocyte macrophage-cell stimulating
                          factor
 SYNONYMS                 rHu GM-CSF [AHFS Drug Information 1995]
 SYNONYMS                 Leukine [PDR 1995]
 SYNONYMS                 Prokine [PDR 1993]
 PROTOCOL ID NUMBERS      NIAID ACTG 065
 PROTOCOL ID NUMBERS      NIAID ACTG 073
 PROTOCOL ID NUMBERS      NIAID ACTG 074
 PROTOCOL ID NUMBERS      NIAID ACTG 090
 PROTOCOL ID NUMBERS      NIAID ACTG 142
 PROTOCOL ID NUMBERS      NIAID ACTG 094
 PROTOCOL ID NUMBERS      NIAID 88 I-181
 PROTOCOL ID NUMBERS      NCI 88 C-130
 PROTOCOL ID NUMBERS      NCI 88 C-177
 PROTOCOL ID NUMBERS      NCI 90 C-34
 PROTOCOL ID NUMBERS      FDA 005A
 PROTOCOL ID NUMBERS      FDA 067A
 PROTOCOL ID NUMBERS      FDA 067B
 PROTOCOL ID NUMBERS      FDA 067C
 PROTOCOL ID NUMBERS      FDA 067D
 PROTOCOL ID NUMBERS      FDA 067E
 SECONDARY SOURCE ID      SCH 39300 [NIAID ACTG 142]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: GM-CSF is multilineage
                          colony-stimulating factor that principally
                          affects proliferation, differentiation and
                          activation of granulocytes and macrophages by
                          inducing partially committed progenitor cells
                          to divide and differentiate in the
                          granulocyte-macrophage pathways. Endogenous
                          human GM-CSF is produced by both hematologic
                          and tissue cells. It acts on various
                          progenitor target cells by binding to
                          GM-CSF-specific bindig sites on their
                          surfaces; biosynthetic GM-CSF products have
                          similar mechanisms of action. The increase in
                          leukocyte count in response to GM-CSF therapy
                          is dose dependent. Serum concentrations
                          appear to decline in a biphasic manner.
                          Elimination characteristics of the drug,
                          including possible metabolic pathways and/or
                          excretion mechanisms remain to be fully
                          explored. [AHFS Drug Information 1995] In
                          vitro, Leukine  (Immunex tradename for
                          yeast-derived GM-CSF) increases the
                          cytotoxicity of monocytes towards certain
                          neoplastic cell lines and activates
                          polymorphonuclear neutrophils to inhibit the
                          growth of tumor cells. In human trials, peak
                          levels of subcutaneously administered Leukine
                          were observed 2 hours after injection (range:
                          350-3,900 pg/ml); the substance remained at
                          detectable levels, 6 hours after injection.
                          [PDR 1995]
 DISEASES STUDIED/TREATED Used to correct or minimize HIV-associated
                          neutropenia and/or drug-induced neutropenia
                          (i.e., due to treatment with zidovudine,
                          interferon alfa, or cytotoxic chemotherapy)
                          [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Used to increase neutrophil counts in
                          patients with CMV infection who develop
                          neutropenia while on ganciclovir, and
                          patients with nonmalignant conditions who
                          develop neutropenia while on myelosuppressive
                          drugs. [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED FDA approved 3/5/91 for cancer patients with
                          lymphomas or leukemia who are receiving bone
                          marrow transplants [HHS Press Release]
 CLASSIFICATION CODE      Antineutropenic [USAN 1995]
 CLASSIFICATION CODE      Hematopoietic Stimulant [USAN 1995]
 OTHER MAJOR USES         Used to accelerate myeloid recovery in adults
                          with non-Hodgkin's lymphoma, acute
                          lymphocytic (lymphoblastic) leukemia or
                          Hodgkin's disease undergoing cytotoxic
                          chemotherapy and autologous bone marrow
                          transplantation (BMT). Also used in adults
                          with chronic myelogenous leukemia, acute
                          nonlymphocytic leukemia or severe aplastic
                          anemia undergoing allogenic BMT [AHFS Drug
                          Information 1995]
 SUBSTANCE INTERACTIONS   Safety and efficacy of concomitant
                          administration with radiation therapy or with
                          myelosuppressive antineoplastic agents have
                          not been established. Because specific
                          studies have not been performed to evaluate
                          the additive effects of myeloproliferative
                          drugs, such combinations should be used with
                          caution in patients receiving GM-CSF. In
                          vitro studies indicate that GM-CSF may
                          potentiate the antiretroviral activity of
                          zidovudine. Human studies on such
                          combinations are ongoing. [AHFS Drug
                          Information 1995]
 ADVERSE EFFECTS          GM-CSF is generally well tolerated. In some
                          patients with preexisting renal or hepatic
                          dysfunctions, administration of the drug
                          caused elevation of serum creatinine or
                          bilirubin and hepatic enzymes. In some
                          patients there were reports of headache,
                          arthralgia, myalgia, fever, bone pain, and
                          chills. These effects were generally mild or
                          moderate and could be alleviated with drugs
                          such as acetaminophen. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with excessive
                          leukemic myeloid blasts in the bone marrow or
                          peripheral blood (>10%). Should be used with
                          caution in patients with preexisting fluid
                          retention, pulmonary infiltrates, or cardiac
                          disease. It should also be used with caution
                          in patients with preexisting renal or hepatic
                          dysfunctions. The drug should be given to
                          pregnant women or nursing mothers only if
                          clearly needed. The drug does not exhibit any
                          greater toxicity in children (4 months to 18
                          years of age) than in adults. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A single chain,
                          glycosylated polypeptide of 127 amino acid
                          residues expressed from Saccharomyces
                          cerevisiae [USAN 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The glycoprotein is
                          represented by three molecular species having
                          relative molecular weights of approximately
                          19,500, 16,800 and 15,500 due to different
                          levels of glycosylation [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA:C639, H1002, N168, O196, S8
                          [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 15,500-19,500 daltons [USAN
                          1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: To avoid physical and chemical
                          incompatibilities do not mix with other drugs
                          in infusion solutions. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Sterile lyophilized
                          powder [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials containing 250 or 500 mcg.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous injection,
                          intravenous infusion. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: The sterile powder, the
                          reconstititued solution and the diluted
                          solutions for injection should be
                          refrigerated at 2-8 C (36-46 F). Do not shake
                          or freeze. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Discard any unused solution after 6
                          hours. [PDR 1995]
 MANUFACTURERS            Schering-Plough
 REFERENCES               Hill AD, Naama HA, Calvano SE, Daly JM. The
                          effect of granulocyte-macrophage
                          colony-stimulating factor on myeloid cells
                          and its clinical applications. J Leukoc Biol.
                          1995 Dec;58(6):634-42.
 REFERENCES               Castello G, Mela G, Cerruti A, Mencoboni M,
                          Lerza R. Azidothymidine and interferon-alpha
                          in vitro effects on hematopoiesis: protective
                          in vitro activity of IL-1 and GM-CSF. Exp
                          Hematol. 1995 Dec;23(13):1367-71.
 REFERENCES               Matsuda S, Akagawa K, Honda M, Yokota Y,
                          Takebe Y, Takemori T. Suppression of HIV
                          replication in human monocyte-derived
                          macrophages induced by granulocyte/macrophage
                          colony-stimulating factor. AIDS Res Hum
                          Retroviruses. 1995 Sep;11(9):1031-8.
 REFERENCES               Manfredi R, Cariani T, Latini F, Chiodo F.
                          Recombinant granulocyte-macrophage
                          colony-stimulating factor in the treatment of
                          HIV-related leucopenia. Acta Paediatr. 1995
                          Aug;84(8):943-4.
 REFERENCES               Price P, Johnson RP, Scadden DT, Jassoy C,
                          Rosenthal T, Kalams S, Walker BD. Cytotoxic
                          CD8+ T lymphocytes reactive with human
                          immunodeficiency virus-1 produce
                          granulocyte/macrophage colony-stimulating
                          factor and variable amounts of interleukins
                          2,3, and 4 following stimulation with the
                          cognate epitope. Clin Immunol Immunopathol.
                          1995 Jan;74(1):100-6.
 REFERENCES               Gallicchio VS, Hughes NK. Influence of human
                          granulocyte-macrophage colony stimulation
                          factor/interleukin-3 fusion protein (PIXY321)
                          on the hematopoietic toxicity associated with
                          anti-viral drugs (zidovudine and didanosine)
                          in vitro using normal human marrow cells.
                          Life Sci. 1995;57(18):PL265-73.
 REFERENCES               Uittenbogaart CH, Anisman DJ, Zack JA,
                          Economides A, Schmid I, Hays EF. Effects of
                          cytokines on HIV-1 production by thymocytes.
                          Thymus. 1994-95;23(3-4):155-75.
 REFERENCES               Bergamini A, Perno CF, Dini L, Capozzi M,
                          Pesce CD, Ventura L, Cappannoli L, Falasca L,
                          Milanese G, Calio R, et al. Macrophage
                          colony-stimulating factor enhances the
                          susceptibility of macrophages to infection by
                          human immunodeficiency virus and reduces the
                          activity of compounds that inhibit virus
                          binding. Blood. 1994 Nov 15;84(10):3405-12.
 REFERENCES               Piguet D, Chapuis B. Recombinant human
                          granulocyte-macrophage colony-stimulating
                          factor in acquired or chemotherapy-induced
                          neutropenia. An open clinical trial. Acta
                          Oncol. 1994;33(6):639-43.
 REFERENCES               Henrivaux P, Fairon Y. Pharmacokinetics of
                          GM-CSF and early leucocyte response after
                          subcutaneous (SC) GM-CSF administration to
                          AIDS patients. Int Conf AIDS. 1994 Aug
                          7-12;10(1):223 (abstract no. PBO321).
 ENTRY MONTH              8906
 LAST REVISION DATE       960502
 

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