      Document 0121
 DOCN  DRG0121
 UNIQUE IDENTIFIER        DRG-0126
 NAME OF SUBSTANCE        Lamivudine [USAN 1996]
 REGISTRY NUMBER          134678-17-4
 STANDARD CHEMICAL NAME   2(1H)-Pyrimidinone,4-amino-1-[2-(hydroxymethy-
                          l)-1,3- oxathiolan-5-yl]-, (2R-cis)- [USAN
                          1996]
 SYNONYMS                 GR-109714X [USAN 1996]
 SYNONYMS                 3TC [AmFAR Tx Dir 1995;7(4)]
 SYNONYMS                 2'-Deoxy-3'-thiacytidine [J Infect Dis 1995
                          Jun;171(6)]
 SYNONYMS                 Epivir [FDA Talk Paper]
 PROTOCOL ID NUMBERS      NCI 91 C-198
 PROTOCOL ID NUMBERS      NCI 92 C-96D
 PROTOCOL ID NUMBERS      FDA 129D
 PROTOCOL ID NUMBERS      NCI 94 C-35
 PROTOCOL ID NUMBERS      FDA 129B
 PROTOCOL ID NUMBERS      FDA 129C
 PROTOCOL ID NUMBERS      NIAID ACTG 300
 PROTOCOL ID NUMBERS      FDA 246E
 PROTOCOL ID NUMBERS      NIAID ACTG 302
 PROTOCOL ID NUMBERS      NIAID ACTG 306
 PROTOCOL ID NUMBERS      NIAID ACTG 320
 PROTOCOL ID NUMBERS      NCI 95 C-163
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: 3TC, like other nucleoside
                          analogs, is presumed to inhibit HIV
                          replication through viral DNA chain
                          termination. Food delays the absorption of
                          3TC administered orally; however, it does not
                          significantly alter its bioavailability. Dose
                          linearity was observed for both maximum
                          concentration and the AUC. These parameters
                          were relatively unchanged after 24 wk of
                          continuous dosing. Even at lower doses, peak
                          concentrations well above the IC90 were
                          achieved. [AmFAR Tx Dir 1995;7(4)] [Int Conf
                          AIDS 1992 Jul 19-24;8(2): (abstract no PoB
                          3008)] [J Infect Dis 1995 Jun;171(6)]
 DISEASES STUDIED/TREATED FDA approved 11/20/95 in combination with AZT
                          for treatment of AIDS and HIV infection [HHS
                          Press Release]
 CLASSIFICATION CODE      Antiretroviral [AmFAR Tx Dir 1995;7(4)]
 ADVERSE EFFECTS          In a clinical study with patients receiving
                          20 mg/kg/day, 6/15 patients developed grade 3
                          neutropenia. Insomnia and rash have been
                          reported. Diarrhea, headache, fatigue and
                          fever have also been reported. Other adverse
                          reactions possibly associated with 3TC
                          include vasculitis, photophobia, and
                          upper-extremity paresthesia. Painful
                          peripheral neuropathy and a possible seizure
                          occurred in patients receiving 8 mg/kg/day.
                          [AmFAR Tx Dir 1995;7(4)] [Lancet 1995 Feb
                          18;345(8947)] [J Infect Dis 1995 Jun;171(6)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: 3TC is composed of the (-)
                          enantiomer of the racemic mixture
                          2'deoxy-3'thiacytidine (BCH189) [AmFAR Tx Dir
                          1995;7(4)] [J Infect Dis 1995 Jun;171(6)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Lamivudine is a
                          dideoxypyrimidine on which the 3' carbon of
                          the ribose ring is replaced by a sulfur atom
                          [AmFAR Tx Dir 1995;7(4)] [J Infect Dis 1995
                          Jun;171(6)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C8H11N3O3S [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 229.26 [USAN 1996]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [AmFAR Tx Dir
                          1995;7(4)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Oral. [J Infect Dis 1995
                          Jun;171(6)]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Pluda JM, Cooley TP, Montaner JS, Shay LE,
                          Reinhalter NE, Warthan SN, Ruedy J, Hirst HM,
                          Vicary CA, Quinn JB, et al. A phase I/II
                          study of 2'-deoxy-3'-thiacytidine
                          (lamivudine) in patients with advanced human
                          immunodeficiency virus infection. J Infect
                          Dis. 1995 Jun;171(6):1438-47.
 REFERENCES               van Leeuwen R, Katlama C, Kitchen V, Boucher
                          CA, Tubiana R, McBride M, Ingrand D, Weber J,
                          Hill A, McDade H, et al. Evaluation of safety
                          and efficacy of 3TC (lamivudine) in patients
                          with asymptomatic or mildly symptomatic human
                          immunodeficiency virus infection: a phase
                          I/II study. J Infect Dis. 1995
                          May;171(5):1166-71.
 REFERENCES               Benhamou Y, Dohin E, Lunel-Fabiani F, Poynard
                          T, Huraux JM, Katlama C, Opolon P, Gentilini
                          M. Efficacy of lamivudine on replication of
                          hepatitis B virus in HIV-infected patients
                          [letter]. Lancet. 1995 Feb
                          11;345(8946):396-7.
 REFERENCES               Dudley MN. Clinical pharmacokinetics of
                          nucleoside antiretroviral agents. J Infect
                          Dis. 1995 Mar;171 Suppl 2:S99-112.
 REFERENCES               van Leeuwen R, Boucher C, Reiss P, Schuurman
                          R, Nijhuis M, Danner S. Safety and efficacy
                          of ZDV addition to 3TC monotherapy. Int Conf
                          AIDS. 1994 Aug 7-12;10(1):21 (abstract no.
                          057B).
 REFERENCES               Lewis L, Wells M, Church J, Wheeler S, Hall
                          S, Pizzo P. A phase I/II study of 3TC
                          (GR109714X) in children with HIV infection.
                          Int Conf AIDS. 1993 Jun 6-11;9(1):478
                          (abstract no. PO-B26-2059).
 REFERENCES               Danner S, van Leeuwen R, Katlama C, Ingrand
                          D, Weber J, Kitchen V. 3TC in HIV positive,
                          asymptomatic or mild ARC patients. Int Conf
                          AIDS. 1993 Jun 6-11;9(1):477 (abstract no.
                          PO-B26-2054).
 REFERENCES               van Leeuwen R, Lange JM, Hussey EK, Donn KH,
                          Hall ST, Harker AJ, Jonker P, Danner SA. The
                          safety and pharmacokinetics of a reverse
                          transcriptase inhibitor, 3TC, in patients
                          with HIV infection: a phase I study. AIDS
                          1992 Dec;6(12):1471-5.
 REFERENCES               Pluda J, Ruedy J, Levitt N, Cooley T, Berard
                          P, Rubin M, Yarchoan R. Phase I/II study of
                          3TC in patients with advanced ARC or AIDS.
                          Int Conf AIDS. 1992 Jul 19-24;8(2):B91
                          (abstract no. PoB 3026).
 REFERENCES               Angel JB, Hussey EK, Mydlow PK, Morris DM,
                          McCormack IP, Montaner JS, Ruedy J.
                          Pharmacokinetics of GR109714X (3TC) HIV
                          infected patients when administered with and
                          without food. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B88 (abstract no. PoB 3008).
 ENTRY MONTH              9111
 LAST REVISION DATE       960612
 

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