      Document 0209
 DOCN  DRG0209
 UNIQUE IDENTIFIER        DRG-0038
 NAME OF SUBSTANCE        Cytarabine [USAN 1995]
 REGISTRY NUMBER          147-94-4
 REGISTRY NUMBER          69-74-9
 RELATED REGISTRY NUMBER  69-74-9
 STANDARD CHEMICAL NAME   4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrim-
                          idinone [USAN 1995]
 SYNONYMS                 Cytosar-U (Upjohn) [USAN 1995]
 SYNONYMS                 Tarabine (Adria) [USAN 1995]
 SYNONYMS                 Beta-cytosine arabinoside [Merck Index 1989]
 SYNONYMS                 Alexan [Merck Index 1989]
 SYNONYMS                 Arabitin [Merck Index 1989]
 SYNONYMS                 Aracytidine [Merck Index 1989]
 SYNONYMS                 Ara-C [PDR 1995]
 SYNONYMS                 Cytosar [Merck Index 1989]
 SYNONYMS                 Erpalfa [Merck Index 1989]
 SYNONYMS                 Iretin [Merck 1989]
 SYNONYMS                 Udicil [Merck Index 1989]
 SYNONYMS                 Cytosar-U Sterile Powder [PDR 1995]
 SYNONYMS                 1-Beta-D-arabinofuranosylcytosine [PDR 1989]
 SYNONYMS                 Aracytine [Merck Index 1989]
 SYNONYMS                 Cytarabine Hydrochloride:
                          1-Beta-D-arabinofuranosylcytosine
                          monohydrochloride [USAN 1995]
 SYNONYMS                 Cytosine Arabinoside Hydrochloride [USAN
                          1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 008
 PROTOCOL ID NUMBERS      NIAID ACTG 074
 PROTOCOL ID NUMBERS      NCI 90 C-34
 PROTOCOL ID NUMBERS      NIAID ACTG 142
 PROTOCOL ID NUMBERS      NCI 93 C-207
 PROTOCOL ID NUMBERS      NIAID ACTG 243
 PROTOCOL ID NUMBERS      NIAID ACTG 252
 SECONDARY SOURCE ID      U-19,920 (Cytarabine) [USAN 1995]
 SECONDARY SOURCE ID      U-19920A [USAN 1995]
 SECONDARY SOURCE ID      NSC-63878 [USAN 1995]
 SECONDARY SOURCE ID      69-74-9 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Cytarabine is cytotoxic,
                          killing cells undergoing DNA synthesis in the
                          S phase of cell division. Toxicity is
                          probably due to the inhibition of DNA
                          polymerase. Following rapid intravenous
                          injection, disappearance from plasma is
                          biphasic (initial distributive phase with a
                          half-life of about 10 minutes, followed by a
                          second elimination phase of about 1-3 hours;
                          after the distributive phase, over 80 percent
                          of the drug in plasma is in the form of the
                          inactive metabolite,
                          1-beta-D-arabinofuranosyluracil (ara-U);
                          within about 24 hours, 80 percent of the dose
                          is recovered in urine, 90 percent of which is
                          in the form of ara-U. Relatively constant
                          plasma levels can be obtained by continuous
                          intravenous infusion. After subcutaneous or
                          intramuscular injection, peak plasma levels
                          are reached in 20-60 minutes, and are lower
                          than for intravenous administration.
                          Cerebrospinal fluid (CSF) levels are low
                          relative to plasma levels after intravenous
                          injection, with little conversion to ara-U.
                          With intrathecal administration, CSF
                          Cytarabine levels decline with a first order
                          half-life of about 2 hours. It is not
                          effective orally (less than 20 percent is
                          absorbed from the gastrointestinal tract).
                          [PDR 1995]
 DISEASES STUDIED/TREATED Prophylaxis for Non-Hodgkin's lymphoma to
                          prevent dissemination of the disease. Under
                          investigation for the treatment of
                          Progressive Multifocal Leukoencephalopathy
                          (PML) [AmFAR Tx Dir 1995;1(4)]
 CLASSIFICATION CODE      Antineoplastic [USAN 1995]
 CLASSIFICATION CODE      Antiviral [USAN 1995]
 CLASSIFICATION CODE      Antimetabolite [USP DI 1995]
 CLASSIFICATION CODE      Immunosuppressant [USP DI 1995]
 OTHER MAJOR USES         In combination with other approved anticancer
                          drugs is indicated in remission induction in
                          acute nonlymphocytic leukemia of adults and
                          children. It is also useful in the treatment
                          of acute lymphocytic leukemia and the blast
                          phase of chronic myelocytic leukemia.
                          Intrathecal administration is indicated in
                          the prophylaxis and treatment of meningeal
                          leukemia [PDR 1995]
 SUBSTANCE INTERACTIONS   Digoxin absorption may be decreased by
                          concomitant cytarabine. Gentamicin and
                          fluorocytosine activity may also be inhibited
                          by cytarabine. [PDR 1995]
 ADVERSE EFFECTS          Its main toxic effect is bone marrow
                          suppression with anemia, leukopenia, and
                          thrombocytopenia (since it is a potent bone
                          marrow suppressant, it should be started
                          cautiously in patients with pre-existing
                          drug-induced bone marrow suppression). Other
                          adverse effects may include: megaloblastosis,
                          reduced reticulocytes, fever, myalgia, bone
                          pain, occasional chest pain, maculopapular
                          rash, conjunctivitis, malaise, hepatic
                          dysfunction, thrombophlebitis, bleeding,
                          anorexia, nausea, vomiting, diarrhea, or
                          oral/anal inflammation and ulceration. There
                          is no antidote for overdose; overdose can
                          result in irreversible central nervous system
                          toxicity and death. Should only be used by
                          physicians experienced in cancer
                          chemotherapy. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in those patients who are
                          hypersensitive to the drug. Since the drug
                          has shown to be potentially teratogenic, it
                          should be used with women who are pregnant or
                          who may become pregnant only after due
                          consideration of its benefits and hazards.
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthetic pyrimidine
                          nucleoside [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C9H13N3O5; Cytarabine
                          Hydrochloride: C9H13N3O5.HCl [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 243.22; Cytarabine
                          Hydrochloride: 279.68 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C44.44%;
                          H5.39%; N17.28%; O32.89% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 212-213 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Freely soluble in water; slightly
                          soluble in alcohol and in chloroform [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Odorless, white to
                          off-white, crystalline powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Molecular formula
                          (Cytarabine Hydrochloride: C9-H13-N3-05.HC1);
                          Molecular weight (Cytarabine Hydrochloride:
                          279.68) [USAN 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 100 mg, 500 mg, 1 g and 2 g
                          vials. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous, intrathecal,
                          or subcutaneous injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Solutions reconstituted with
                          bacteriostatic water for injection with
                          benzyl alcohol may be stored at 15 C to 30 C
                          for 48 hours. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Solutions reconstituted with water
                          for injection should be used immediately.
                          [PDR 1995]
 MANUFACTURERS            Upjohn
 REFERENCES               PML--update. Crit Path AIDS Proj. 1994-95
                          Winter;30:28-9.
 REFERENCES               Ravaux I, Quinson AM, North MO, Gallais H.
                          Treatment  of AIDS and progressive multifocal
                          leucoencephalopathy (PML) with cytarabine
                          when the brain biopsy is unsuccessful or
                          impossible. Int Conf AIDS. 1994 Aug
                          7-12;10(1):201 (abstract no. PB0231).
 REFERENCES               Greenberg AL, Droller DG. Successful
                          treatment of a patient with seropositive
                          human immunodeficiency virus with high risk
                          Burkitt's leukemia. Cancer. 1994 Aug
                          15;74(4):1261-4.
 REFERENCES               Hervas Laguna MJ, Nieto Rodriguez JA, Geijo
                          Martinez MP, Ruiz Ribo MD, Borregon S.
                          [Progressive multifocal leukoencephalpathy
                          and AIDS. Response to cytarabine]. An Med
                          Interna. 1994 May;11(5):241-3.
 REFERENCES               Urtizberea JA, Flament-Saillour M, Clair B,
                          de Truchis P. Cytarabine for progressive
                          multifocal leucoencephalopathy (PML) in AIDS
                          patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):421 (abstract no. PO-B16-1717).
 REFERENCES               Chamberlain MC, Dirr L. Involved-field
                          radiotherapy and intra-Ommaya
                          methotrexate/cytarabine in patients with
                          AIDS-related lymphomatous meningitis. J Clin
                          Oncol. 1993 Oct;11(10):1978-84.
 REFERENCES               Britton CB, Romagnoli M, Sisti M, Powers JM.
                          Progressive multifocal leukoencephalopathy:
                          disease progression, stabilization and
                          response to intrathecal Ara-C in 26 patients.
                          Int Conf AIDS. 1992 Jul 19-24;8(1):Th67
                          (abstract no. ThB 1512).
 REFERENCES               Philip T, Meckenstock R, Deconnick E, Carrie
                          C, Bailly C, Colombat P, Dauriac C, Demaille
                          MC, Salles B, Cahn JY, et al. Treatment of
                          poor prognosis Burkitt's lymphoma in adults
                          with the Societe Francaise d'Oncologie
                          Pediatrique LMB Protocol--a study of the
                          Federation Nationale des Centres de Lutte
                          Contre le Cancer (FNLCC). Eur J Cancer.
                          1992;28A(12):1954-9.
 REFERENCES               Portegies P, Reiss P, Algra PR, Hollak CE,
                          Prins JM, Valk J, Lange J. Progressive
                          multifocal leukoencephalopathy in AIDS:
                          favourable response to cytosine arabinoside
                          in three patients. Int Conf AIDS. 1991 Jun
                          16-21;7(1):191 (abstract no. M.B.2037).
 REFERENCES               Mazza JJ, Hines JD, Anderson JW, O'Connell
                          MJ. TREATMENT OF BURKITT'S AND
                          UNDIFFERENTIATED NON-BURKITT'S LYMPHOMA USING
                          INTENSIFICATION HIGH-DOSE ARA-C AND EXTENDED
                          CONSOLIDATION CHEMOTHERAPY. AN ECOG STUDY
                          (MEETING ABSTRACT). Proc Annu Meet Am Soc
                          Clin Oncol. 1990:9;A1010.
 ENTRY MONTH              8906
 LAST REVISION DATE       950905
 

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