      Document 0201
 DOCN  DRG0201
 UNIQUE IDENTIFIER        DRG-0046
 NAME OF SUBSTANCE        Vincristine [Merck Index 1989]
 REGISTRY NUMBER          57-22-7
 RELATED REGISTRY NUMBER  2068-78-2
 STANDARD CHEMICAL NAME   22-Oxovincaleukoblastine [CHEMLINE]
 SYNONYMS                 VCR [Merck Index 1989]
 SYNONYMS                 LCR [Merck Index 1989]
 SYNONYMS                 Vincristine Sulfate [USAN 1996]
 SYNONYMS                 Vincasar [USAN 1996]
 SYNONYMS                 Oncovin [USAN 1996]
 SYNONYMS                 Vincaleukoblastine, 22-oxo-, sulfate (1:1)
                          [USAN 1996]
 SYNONYMS                 Leurocristine Sulfate (1:1) [USAN 1996]
 SYNONYMS                 Kyocristine [Merck Index 1989]
 SYNONYMS                 Leurocristine [Merck Index 1989]
 SYNONYMS                 Vincrex [USAN 1996]
 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      FDA 121A
 PROTOCOL ID NUMBERS      FDA 134A
 PROTOCOL ID NUMBERS      FDA 134B
 PROTOCOL ID NUMBERS      NIAID ACTG 252
 PROTOCOL ID NUMBERS      NIAID ACTG 163
 PROTOCOL ID NUMBERS      NIAID ACTG 286
 SECONDARY SOURCE ID      NSC-67574 [USAN 1996]
 SECONDARY SOURCE ID      37231 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Unknown but evidence
                          indicates that it may cause an arrest of
                          mitotic division at the stage of metaphase;
                          antineoplastic effects are related to
                          interference with intracellular tubulin
                          function; does not appear to penetrate well
                          into the cerebrospinal fluid.  May interfere
                          with amino acid metabolism; it is cell-cycle
                          specific for the M phase of cell division.
                          Vincristine is poorly abused orally. After
                          intravenous use, plasma elimination is
                          triphasic with half-lives of 0.08, 2.3, and
                          85 hours. The drug is incompletely
                          metabolized by the liver and elimination is
                          primarily via the bile; aprroximately 70% of
                          a dose is excreted in the feces and about 12%
                          is eliminated in the urine. Obstruction of
                          liver outflow may require careful adjustment
                          of dosage. Vincristine does not penetrate the
                          central nervous system. [PDR 1995] [USP DI
                          1995]
 DISEASES STUDIED/TREATED Kaposi's sarcoma [AmFAR Tx Dir 1995;7(4)]
 DISEASES STUDIED/TREATED Lymphomas [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Indicated in acute leukemia and in
                          combination with other oncolytic agents for
                          treating Hodgkin's disease, non-Hodgkin's
                          lymphoma, rhabdomyosarcoma, neuroblastoma,
                          and Wilms' tumor [PDR 1995]
 SUBSTANCE INTERACTIONS   Combinations of phenytoin and antineoplastic
                          agents, including vincristine, have reduced
                          phenytoin blood levels and increased seizure
                          activity. Myelosuppression has been reported
                          with combinations of vincristine, doxorubicin
                          and prednisone. Vincristine induced
                          hyperuricemia can occur with concomitant
                          sulfinpyrazone. Additive neurotoxicity can
                          occur with vincristine and asparaginase.
                          Immunization procedures should be avoided,
                          especially with live virus vaccines. [PDR
                          1995]
 ADVERSE EFFECTS          FATAL IF GIVEN INTRATHECALLY. Its major side
                          effects include neurotoxicity and rare
                          myelosuppression. Adverse reactions generally
                          are reversible with the most common being
                          hair loss and the most troublesome being
                          neuromuscular in origin; may also cause
                          leukopenia, anemia, thrombocytopenia,
                          neuritic pain, constipation, difficulty in
                          walking, sensory loss, paresthesia, slapping
                          gait, loss of deep-tendon reflexes, muscle
                          wasting, paralytic ileus in young children,
                          convulsions, hypertension, abdominal cramps,
                          ataxia, foot drop weight loss, hypotension,
                          rash, optic atrophy with blindness, transient
                          cortical blindness, fever, numbness of the
                          digits, oral ulceration, headache, nausea,
                          vomiting, anorexia, diarrhea, intestinal
                          necrosis and/or perforation, bladder atony,
                          cranial nerve manifestations, jaw pain,
                          pharyngeal pain, parotid gland pain, bone
                          pain, back pain, limb pain, myalgias. [PDR
                          1995]
 CONTRAINDICATIONS        Should not be given to patients with
                          demyelinating form of Charcot Marie Tooth
                          syndrome. Caution should be exercised when
                          administering vincristine to patients with
                          preexisting neuromuscular disease and when
                          other drugs with neurotoxic potential are
                          being used. Vincristine can cause fetal harm,
                          pregnant women receiving this drug should be
                          apprised of the potential hazard to the
                          fetus. In breast-feeding women, a decision
                          should be made to discontinue breast-feeding
                          or the drug since it is not known whether it
                          is excreted in breast milk. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Alkaloid obtained from the
                          periwinkle plant, Vinca rosea [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C46H56N4O10 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 824.94 (Vincristine) [Merck
                          Index 1989]; 923.04 (Vincristine Sulfate)
                          [USAN 1993]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C66.97%; H6.84%;
                          N6.79%; O19.40% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 218-220 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white or
                          slightly yellow, hygroscopic, amorphous or
                          crystalline powder [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Vincristine sulfate for injection
                          is stable for 14 days when refrigerated; do
                          not dilute with solutions that alter the pH
                          range of 3.5 to 5.5. Use only 0.9% sodium
                          chloride or 5% dextrose injection as diluents
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKas 5 and 7.4 [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 1 ml, 2 ml, and 5 ml multiple
                          dose vials containing 1 mg/ml. Disposable
                          syringes, 1 ml and 2 ml, containing 1 mg/ml.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Fatal if given
                          intrathecally.Intravenous injection/infusion.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Should be refrigerated between 2-8 C
                          (36-46 F). [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store in a light-resistant, glass
                          container. [USP DI 1995]
 MANUFACTURERS            Adria Laboratories
 MANUFACTURERS            Quad Pharmaceuticals
 MANUFACTURERS            Eli Lilly
 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               Lingefelser T, Daiss W, Overkamp D, Weber P.
                          Successful monochemotherapy of extensive
                          gastrointestinal Kaposi's sarcoma with bowel
                          obstruction in acquired immunodeficiency
                          syndrome. Z Gastroenterol. 1994
                          Dec;32(12):688-90.
 REFERENCES               Gompels MM, Hill A, Jenkins P, Peters B, et
                          al. Kaposi's sarcoma in HIV infection treated
                          with vincristine and bleomycin [published
                          erratum appears in AIDS 1992
                          Nov;6(11):following 1410].
 REFERENCES               Nagatani T, Miyazawa M, Matsuzaki T, Iemoto
                          G, Kim S, Baba N, Miyakawa K, Miyamoto H,
                          Nakajima H, Hirai Y. Successful treatment of
                          adult T-cell leukemia/lymphoma with MACOP-B,
                          M-FEPA and VEPP-B combination chemotherapy. J
                          Dermatol. 1993 Oct;20(10):623-9.
 REFERENCES               Lipman MC, Swaden LS, Sabin CA, Collis C,
                          Johnson MA. Kaposi's sarcoma in HIV infection
                          treated with vincristine and bleomycin
                          [letter; comment]. AIDS. 1993 Apr;7(4):592-3.
 REFERENCES               Ireland-Gill A, Espina BM, Akil B, Gill PS.
                          Treatment of acquired immunodeficiency
                          syndrome-related Kaposi's sarcoma using
                          bleomycin-containing combination chemotherapy
                          regimens. Semin Oncol. 1992 Apr;19(2 Suppl
                          5):32-6;discussion 36-7.
 REFERENCES               Taillan B, Pesce A, Garnier G, Vinti H,
                          Fuzibet JG, Cassuto JP, Dujardin P. AIDS
                          related malignant lymphoma: results of MACOP
                          B chemotherapy. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B108 (abstract no. PoB 3127).
 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 chenotherapy
                          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.
 REFERENCES               Kaplan LD, Kahn JO, Crowe S, Northfelt D,
                          Neville P, Grossberg H, Abrams DI, Tracey J,
                          Mills J, Volberding PA. Clinical and
                          virologic effects of recombinant human
                          granulocyte-macrophage colony-stimulating
                          factor in patients receiving chemotherapy for
                          human immunodeficiency virus-associated
                          non-Hodgkin's lymphoma: results of a
                          randomized trial. J Clin Oncol. 1991
                          Jun;9(6):929-40.
 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.
 ENTRY MONTH              8906
 LAST REVISION DATE       950908
 

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