      Document 0243
 DOCN  DRG0243
 UNIQUE IDENTIFIER        DRG-0004
 NAME OF SUBSTANCE        Zidovudine [USAN 1995]
 REGISTRY NUMBER          30516-87-1
 STANDARD CHEMICAL NAME   Thymidine, 3'-azido-3'-deoxy- [USAN 1995]
 SYNONYMS                 AZT [USAN 1995]
 SYNONYMS                 Azidothymidine [USAN 1995]
 SYNONYMS                 Retrovir [USAN 1995]
 SYNONYMS                 3'-Azido-3'-deoxythymidine [USAN 1995]
 SYNONYMS                 ZDV [NIAID ACTG 184]
 PROTOCOL ID NUMBERS      NIAID ACTG 001
 PROTOCOL ID NUMBERS      NIAID ACTG 002
 PROTOCOL ID NUMBERS      NIAID ACTG 003
 PROTOCOL ID NUMBERS      NIAID ACTG 004
 PROTOCOL ID NUMBERS      NIAID ACTG 005
 PROTOCOL ID NUMBERS      NIAID ACTG 008
 PROTOCOL ID NUMBERS      NIAID ACTG 009
 PROTOCOL ID NUMBERS      NIAID ACTG 010
 PROTOCOL ID NUMBERS      NIAID ACTG 013
 PROTOCOL ID NUMBERS      NIAID ACTG 014
 PROTOCOL ID NUMBERS      NIAID ACTG 016
 PROTOCOL ID NUMBERS      NIAID ACTG 017
 PROTOCOL ID NUMBERS      NIAID ACTG 019
 PROTOCOL ID NUMBERS      NIAID ACTG 020
 PROTOCOL ID NUMBERS      NIAID ACTG 021
 PROTOCOL ID NUMBERS      NIAID ACTG 024
 PROTOCOL ID NUMBERS      NIAID ACTG 027
 PROTOCOL ID NUMBERS      NIAID ACTG 032
 PROTOCOL ID NUMBERS      NIAID ACTG 033
 PROTOCOL ID NUMBERS      NIAID ACTG 036
 PROTOCOL ID NUMBERS      NIAID ACTG 037
 PROTOCOL ID NUMBERS      NIAID ACTG 042
 PROTOCOL ID NUMBERS      NIAID ACTG 043
 PROTOCOL ID NUMBERS      NIAID ACTG 047
 PROTOCOL ID NUMBERS      NIAID ACTG 049
 PROTOCOL ID NUMBERS      NIAID ACTG 050
 PROTOCOL ID NUMBERS      NIAID ACTG 051
 PROTOCOL ID NUMBERS      NIAID ACTG 052
 PROTOCOL ID NUMBERS      NIAID ACTG 053
 PROTOCOL ID NUMBERS      NIAID ACTG 055
 PROTOCOL ID NUMBERS      NIAID ACTG 057
 PROTOCOL ID NUMBERS      NIAID ACTG 061
 PROTOCOL ID NUMBERS      NIAID ACTG 062
 PROTOCOL ID NUMBERS      NIAID ACTG 063
 PROTOCOL ID NUMBERS      NIAID ACTG 065
 PROTOCOL ID NUMBERS      NIAID ACTG 067
 PROTOCOL ID NUMBERS      NIAID ACTG 068
 PROTOCOL ID NUMBERS      NIAID ACTG 070
 PROTOCOL ID NUMBERS      NIAID ACTG 072
 PROTOCOL ID NUMBERS      NIAID ACTG 073
 PROTOCOL ID NUMBERS      NIAID ACTG 075
 PROTOCOL ID NUMBERS      NIAID ACTG 076
 PROTOCOL ID NUMBERS      NIAID ACTG 079
 PROTOCOL ID NUMBERS      NIAID ACTG 080
 PROTOCOL ID NUMBERS      NIAID ACTG 081
 PROTOCOL ID NUMBERS      NIAID ACTG 082
 PROTOCOL ID NUMBERS      NIAID ACTG 088
 PROTOCOL ID NUMBERS      NIAID ACTG 090
 PROTOCOL ID NUMBERS      NIAID ACTG 094
 PROTOCOL ID NUMBERS      NIAID ACTG 096
 PROTOCOL ID NUMBERS      NIAID ACTG 102
 PROTOCOL ID NUMBERS      NIAID ACTG 103
 PROTOCOL ID NUMBERS      NIAID ACTG 106
 PROTOCOL ID NUMBERS      NIAID ACTG 107
 PROTOCOL ID NUMBERS      NIAID ACTG 112
 PROTOCOL ID NUMBERS      NIAID ACTG 114
 PROTOCOL ID NUMBERS      NIAID ACTG 116
 PROTOCOL ID NUMBERS      NIAID ACTG 117
 PROTOCOL ID NUMBERS      NIAID ACTG 119
 PROTOCOL ID NUMBERS      NIAID ACTG 124
 PROTOCOL ID NUMBERS      NIAID ACTG 128
 PROTOCOL ID NUMBERS      NIAID ACTG 131
 PROTOCOL ID NUMBERS      NIAID ACTG 133
 PROTOCOL ID NUMBERS      NIAID ACTG 134
 PROTOCOL ID NUMBERS      NIAID ACTG 140
 PROTOCOL ID NUMBERS      NIAID ACTG 141
 PROTOCOL ID NUMBERS      NIAID ACTG 143
 PROTOCOL ID NUMBERS      NIAID ACTG 155
 PROTOCOL ID NUMBERS      NIAID ACTG 161
 PROTOCOL ID NUMBERS      NIAID ACTG 168
 PROTOCOL ID NUMBERS      NIAID NS 402
 PROTOCOL ID NUMBERS      NIAID TX 304
 PROTOCOL ID NUMBERS      NIAID 88 EI-199
 PROTOCOL ID NUMBERS      NIAID 88 I-74
 PROTOCOL ID NUMBERS      NIAID 88 I-172
 PROTOCOL ID NUMBERS      NIAID 88 I-181
 PROTOCOL ID NUMBERS      NIAID 89 CC-75
 PROTOCOL ID NUMBERS      NIAID 89 I-139
 PROTOCOL ID NUMBERS      NIAID 90 I-15
 PROTOCOL ID NUMBERS      NIAID 91 I-112
 PROTOCOL ID NUMBERS      NIAID 90 CC-04
 PROTOCOL ID NUMBERS      NCI 86 C-174
 PROTOCOL ID NUMBERS      NCI 86 C-175
 PROTOCOL ID NUMBERS      NCI 87 C-179B
 PROTOCOL ID NUMBERS      NCI 88 C-47
 PROTOCOL ID NUMBERS      NCI 88 C-92
 PROTOCOL ID NUMBERS      NCI 88 C-102
 PROTOCOL ID NUMBERS      NCI 88 C-177
 PROTOCOL ID NUMBERS      NCI 89 C-89
 PROTOCOL ID NUMBERS      NCI 90 C-34
 PROTOCOL ID NUMBERS      NCI 91 C-01
 PROTOCOL ID NUMBERS      NCI 91 C-09
 PROTOCOL ID NUMBERS      NCI 91 C-18
 PROTOCOL ID NUMBERS      NCI 91 C-53
 PROTOCOL ID NUMBERS      FDA 002A
 PROTOCOL ID NUMBERS      FDA 014A through FDA 014L
 PROTOCOL ID NUMBERS      FDA 016A
 PROTOCOL ID NUMBERS      FDA 018A
 PROTOCOL ID NUMBERS      FDA 029F
 PROTOCOL ID NUMBERS      FDA 039B
 PROTOCOL ID NUMBERS      FDA 044A
 PROTOCOL ID NUMBERS      FDA 045A, 045C
 PROTOCOL ID NUMBERS      FDA 052A
 PROTOCOL ID NUMBERS      FDA 052B
 PROTOCOL ID NUMBERS      FDA 057A
 PROTOCOL ID NUMBERS      FDA 061A
 PROTOCOL ID NUMBERS      FDA 067A, 067B
 PROTOCOL ID NUMBERS      FDA 073A
 PROTOCOL ID NUMBERS      FDA 074A
 PROTOCOL ID NUMBERS      FDA 067C
 PROTOCOL ID NUMBERS      FDA 072B
 PROTOCOL ID NUMBERS      FDA 057B
 PROTOCOL ID NUMBERS      NIAID ACTG 162
 PROTOCOL ID NUMBERS      NIAID ACTG 175
 PROTOCOL ID NUMBERS      FDA 031E
 PROTOCOL ID NUMBERS      NIAID CPCRA 007
 PROTOCOL ID NUMBERS      NIAID ACTG 199
 PROTOCOL ID NUMBERS      NIAID ACTG 201
 PROTOCOL ID NUMBERS      NIAID DATRI 003
 PROTOCOL ID NUMBERS      NIAID ACTG 194
 PROTOCOL ID NUMBERS      FDA 116A
 PROTOCOL ID NUMBERS      FDA 052C
 PROTOCOL ID NUMBERS      NIAID ACTG 182
 PROTOCOL ID NUMBERS      NIAID ACTG 197
 PROTOCOL ID NUMBERS      NIAID ACTG 190
 PROTOCOL ID NUMBERS      NIAID ACTG 193
 PROTOCOL ID NUMBERS      NIAID DATRI 002
 PROTOCOL ID NUMBERS      NIAID 93 CC-113
 PROTOCOL ID NUMBERS      NIAID 93 I-109
 PROTOCOL ID NUMBERS      NIAID ACTG 209
 PROTOCOL ID NUMBERS      NIAID ACTG 229
 PROTOCOL ID NUMBERS      NIAID ACTG 236
 PROTOCOL ID NUMBERS      NIAID ACTG 152
 PROTOCOL ID NUMBERS      NIAID ACTG 153
 PROTOCOL ID NUMBERS      NIAID ACTG 176
 PROTOCOL ID NUMBERS      NIAID ACTG 178
 PROTOCOL ID NUMBERS      NIAID ACTG 184
 PROTOCOL ID NUMBERS      NIAID ACTG 187
 PROTOCOL ID NUMBERS      NIAID ACTG 203P
 PROTOCOL ID NUMBERS      NIAID ACTG 213
 PROTOCOL ID NUMBERS      NIAID ACTG 241
 PROTOCOL ID NUMBERS      NIAID ACTG 245
 PROTOCOL ID NUMBERS      NIAID DATRI 003
 PROTOCOL ID NUMBERS      NIAID IRP 011
 PROTOCOL ID NUMBERS      NIAID 93 I-205
 PROTOCOL ID NUMBERS      NIAID 94 I-76
 PROTOCOL ID NUMBERS      NIAID 91 CC-143
 PROTOCOL ID NUMBERS      NIAID ACTG 239
 PROTOCOL ID NUMBERS      NIAID ACTG 240
 PROTOCOL ID NUMBERS      NIAID ACTG 243
 PROTOCOL ID NUMBERS      NIAID ACTG 276
 PROTOCOL ID NUMBERS      NIAID ACTG 290
 PROTOCOL ID NUMBERS      FDA 246E
 PROTOCOL ID NUMBERS      NCI 95 C-83
 PROTOCOL ID NUMBERS      NIAID ACTG 244
 PROTOCOL ID NUMBERS      NIAID ACTG 259
 PROTOCOL ID NUMBERS      NIAID ACTG 260
 PROTOCOL ID NUMBERS      NIAID ACTG 180
 PROTOCOL ID NUMBERS      NIAID ACTG 185
 PROTOCOL ID NUMBERS      NIAID ACTG 193A
 PROTOCOL ID NUMBERS      NIAID ACTG 261
 PROTOCOL ID NUMBERS      NIAID ACTG 262
 PROTOCOL ID NUMBERS      NIAID ACTG 275
 PROTOCOL ID NUMBERS      NIAID DATRI 012
 PROTOCOL ID NUMBERS      FDA 0593E
 PROTOCOL ID NUMBERS      FDA 015H
 PROTOCOL ID NUMBERS      FDA 136A
 PROTOCOL ID NUMBERS      FDA 200B
 PROTOCOL ID NUMBERS      FDA 200C
 PROTOCOL ID NUMBERS      FDA 210A
 PROTOCOL ID NUMBERS      FDA 211A
 PROTOCOL ID NUMBERS      FDA 217B
 PROTOCOL ID NUMBERS      FDA 228B
 PROTOCOL ID NUMBERS      FDA 229B
 PROTOCOL ID NUMBERS      FDA 106A
 PROTOCOL ID NUMBERS      FDA 129B
 PROTOCOL ID NUMBERS      FDA 129C
 PROTOCOL ID NUMBERS      FDA 220A
 PROTOCOL ID NUMBERS      NCI 93 C-155
 PROTOCOL ID NUMBERS      NCI 93 C-192
 PROTOCOL ID NUMBERS      NCI 93 C-207
 PROTOCOL ID NUMBERS      NCI 93 C-21
 PROTOCOL ID NUMBERS      NCI 93 C-70
 PROTOCOL ID NUMBERS      NIC 94 C-35
 PROTOCOL ID NUMBERS      FDA 229C
 PROTOCOL ID NUMBERS      FDA 252A
 PROTOCOL ID NUMBERS      NIAID ACTG 302
 PROTOCOL ID NUMBERS      NIAID ACTG 306
 PROTOCOL ID NUMBERS      NIAID ACTG 298
 PROTOCOL ID NUMBERS      NIAID ACTG 266
 PROTOCOL ID NUMBERS      NIAID ACTG 300
 PROTOCOL ID NUMBERS      NIAID ACTG 320
 PROTOCOL ID NUMBERS      NCI 95 C-163
 PROTOCOL ID NUMBERS      NCI 95 C-183
 PROTOCOL ID NUMBERS      NCI 96 C-3
 PROTOCOL ID NUMBERS      NCI 95 C-184
 IND NUMBER               28,972
 IND NUMBER               30,001
 IND NUMBER               30,005
 IND NUMBER               30,026
 IND NUMBER               31,669
 IND NUMBER               BB2683
 IND NUMBER               BB2928
 IND NUMBER               BB3024
 IND NUMBER               BB3038
 SECONDARY SOURCE ID      U.S. Patent No. 4724232 [PDR 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits HIV replication; due
                          to unavailability of the 3'-azido group for
                          5'-3' phosphodiester bonding, premature viral
                          DNA chain termination occurs.  This drug is
                          phosphorylated by cellular enzymes; in its
                          5'-triphosphate nucleotide form it inhibits
                          HIV enzyme reverse transcriptase. The
                          pharmacokinetics of AZT in children 6 months
                          through 12 years of age are similar to those
                          observed in adult patients. Studies also show
                          that AZT administered orally to children at
                          doses of 120-180 mg/m2 every 6 hours appears
                          to give a side effect profile similar to
                          adults. This is a daily dose of 480-720 mg/m2
                          per day.  May 3, 1990 AZT was FDA approved to
                          treat patients 3 months to 12 years of age
                          who have AIDS or symptoms of advanced
                          infection with the AIDS virus. The
                          recommended dose for long-term AZT use as of
                          900302 is 600 mg/day and if FDA approved for
                          HIV infected people with CD4 cell counts of <
                          500 cells/mm3. Prior to this approval was
                          only for treating people with more advanced
                          stages of HIV infection; those with either an
                          episode of Pneumocystis carinii pneumonia
                          (PCP) or symptomatic and CD4 cell counts <
                          200 cells/mm3. [PDR 1995]
 DISEASES STUDIED/TREATED Primary HIV infection [USP DI 1995]
 DISEASES STUDIED/TREATED FDA approved 3/19/87 for treatment of adult
                          AIDS [USP DI 1995]
 DISEASES STUDIED/TREATED FDA approved 3/2/90 for treatment of adult
                          HIV infection [USP DI 1995]
 DISEASES STUDIED/TREATED FDA approved 5/03/90 for treatment of
                          children with HIV infection [USP DI 1995]
 DISEASES STUDIED/TREATED FDA approved 8/8/94 for HIV-positive women
                          between 14 and 34 months gestation [USP DI
                          1995]\
 DISEASES STUDIED/TREATED FDA approved 8/8/94 (syrup) for newborns of
                          HIV-infected mothers [USP DI 1995]
 CLASSIFICATION CODE      Antiretroviral [PDR 1995]
 SUBSTANCE INTERACTIONS   Coadministration of zidovudine (AZT) with
                          other drugs metabolized by glucuronidation
                          should be avoided because the toxicity of
                          either drug may be potentiated. Acetaminophen
                          may increase the incidence of
                          granulocytopenia. Coadministration of AZT
                          with drugs that are nephrotoxic, cytotoxic,
                          or which interfere with the RBC/WBC number or
                          function such as dapsone, pentamidine,
                          amphotericin B, flucytosine, vincristine,
                          vinblastine, adriamycin, probenecid or
                          interferon may increase the risk of toxicity.
                          Concurrent use of ganciclovir with AZT has
                          caused severe hematologic toxicity.
                          Probenecid may inhibit glucuronidation and/or
                          reduce renal excretion of AZT. Acetaminophen,
                          aspirin, or indomethacin may inhibit
                          glucuronidation. Nucleoside analogues may
                          increase the potential for hematologic
                          toxicity.  Some nucleoside analogues affect
                          DNA replication and antagonize the in vitro
                          antiviral activity of AZT against HIV. [PDR
                          1995]
 ADVERSE EFFECTS          Granulocytopenia and anemia are the most
                          frequent hematologic adverse events in adults
                          and pediatric patients. Platelet count can be
                          both increased or decreased by AZT. Nausea,
                          severe headache, insomnia and myalgia occur
                          in at least 5% of patients. hepatomegaly with
                          steatosis, hepatitis, pancreatitis, lactic
                          acidosis, sensitization reactions,
                          hyperbilirubinemia, vasculitis and seizures
                          are rare reactions. [PDR 1995]
 CONTRAINDICATIONS        Zidovudine is contraindicated for patients
                          who have potentially life-threatening
                          allergic reactions to any of the components
                          of the drug formulation of Retrovir capsules.
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: Thymidine analog in which the
                          3'-hydroxyl group is replaced by an azido
                          group [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H13N5O4 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 267.24 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to beige,
                          odorless, crystalline solid [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 106-112 C [Merck 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C44.94%, H4.90%,
                          N26.21%, O23.95% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: 21.1 mg/ml in water at 25C [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules (100 mg); intravenous,
                          20 ml vials (10 mg/ml);syrup, 240 ml bottles
                          (50 mg/5 ml).
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Retrovir capsules were approved
                          by the FDA in March, 1987. Retrovir syrup
                          received FDA approval in September, 1989.
                          Retrovir intravenous formulation was FDA
                          approved February, 1990.
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous
                          injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store oral and intravenous dosage
                          forms at 15-25 C and protect from light;
                          protect capsules fome moisture. [PDR 1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Simberkoff MS, Hartigan PM, Hamilton JD, Day
                          PL, Diamond GR, Dickinson GM, Drusano GL,
                          Egorin MJ, George WL, Gordin FM, et al.
                          Long-term follow-up of symptomatic
                          HIV-infected patients originally randomized
                          to early versus later zidovudine treatment;
                          report of a Veterans Affairs Cooperative
                          Study. VA Cooperative Study Group on AIDS
                          treatment. J Acquir Immune Defic Syndr Hum
                          Retrovirol. 1996 Feb 1;11(2)142-50.
 REFERENCES               Moore KH, Raasch RH, Brouwer KL, Opheim K,
                          Cheeseman SH, Eyster E, Lemon SM, van der
                          Horst CM. Pharmacokinetics and
                          bioavailability of zidovudine and its
                          glucuronidated metabolite in patients with
                          human immunodeficiency virus infection and
                          hepatic disease (AIDS Clinical Trials Group
                          protocol 062). Antimicrob Agents Chemother.
                          1995 Dec;39(12):2732-7.
 REFERENCES               Eron JJ, Benoit SL, Jemsek J, MacArthur RD,
                          Santana J, Quinn JB, Kuritzkes DR, Fallon MA,
                          Rubin M. Treatment with lamivudine,
                          zidovudine, or both in HIV-positive patients
                          with 200 to 500 CD4+ cells per cubic
                          millimeter. North American HIV Working Party
                          [see comments]. N Engl J Med ; VOL 333, ISS
                          25, 1995, P1662-9.
 REFERENCES               Volberding PA, Lagakos SW, Grimes JM, Stein
                          DS, Rooney J, Meng TC, Fischl MA, Collier AC,
                          Phair JP, Hirsch MS, et al. A comparison of
                          immediate with deferred zidovudine therapy
                          for asymptomatic HIV-infected adults with CD4
                          cell counts of 500 or more per cubic
                          millimeter. AIDS Clininl Trials Group [see
                          comments]. N Engl J Med;VOL 333,ISS
                          7,1995,P401-7.
 REFERENCES               Kinloch-De Loes S, Hirschel BJ, Hoen B,
                          Cooper DA, Tindall B, Carr A, Saurat JH,
                          Clumeck N, Lazzarin A, Mathiesen L, et al. A
                          controlled trial of zidovudine in primary
                          human immunodeficiency virus infection [see
                          comments]. N Engl J Med; VOL 333, ISS 7,
                          1995, P408-13.
 REFERENCES               Montaner JS, Schechter MT, Rachlis A, Gill J,
                          Beaulieu R, Tsoukas C, Raboud J, Cameron B,
                          Salomon H, Dunkle L, et al. Didanosine
                          compared with continued zidovudine therapy
                          for HIV-infected patients with 200 to 500 CD4
                          cells/mm3. A double-blind, randomized,
                          controlled trial. Canadian HIV Trials Network
                          Protocol 002 Study Group. Ann Intern Med; VOL
                          123, ISS 8, 1995, P561-71.
 REFERENCES               Jacobson MA, Gundacker H, Hughes M, Fischl M,
                          Volberding P. Zidovudine side effects as
                          reported by black, Hispanic, and
                          white/non-Hispanic patients with early HIV
                          disease: combined analysis of two multicenter
                          placebo-controlled trials. J Acquir Immune
                          Defic Syndr Hum Retrovirol. 1995 Jan
                          1;11(1):45-52.
 REFERENCES               Sinnwell TM, Sivakumar K, Soueidan S, Jay C,
                          Frank JA, McLaughlin AC, Dalakas MC.
                          Metabolic abnormalities in skeletal muscle of
                          patients receiving zidovudine therapy
                          observed by 31P in vivo magnetic resonance
                          spectroscopy. J Clin Invest; VOL 96, ISS 1,
                          1995, P126-31.
 REFERENCES               Zaretsky MD. AZT toxicity and AIDS
                          prophylaxis: is AZT beneficial for HIV+
                          asymptomatic persons with 500 or more T4
                          cells per cubic millimeter? Genetica; VOL 95,
                          ISS 1-3, 1995, P91-101 (REF:44).
 REFERENCES               Kumar RM, Hughes PF, Khurranna A. Zidovudine
                          use in pregnancy: a report on 104 cases and
                          the occurrence of birth defects. J Acquir
                          Immune Defic Syndr 1994 Oct;7(10):1034-9.
 ENTRY MONTH              8906
 LAST REVISION DATE       960612
 

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