      Document 0239
 DOCN  DRG0239
 UNIQUE IDENTIFIER        DRG-0008
 NAME OF SUBSTANCE        Acyclovir [USAN 1995]
 REGISTRY NUMBER          59277-89-3
 RELATED REGISTRY NUMBER  69657-51-8
 STANDARD CHEMICAL NAME   2-Amino-1,9-dihydro-9-((2
                          hydroxyethoxy)methyl)-6H-purin 6-one [USAN
                          1995]
 SYNONYMS                 Acycloguanosine [Merck Index 1989]
 SYNONYMS                 Aciclovir [USAN 1995]
 SYNONYMS                 Wellcome-248U [Merck Index 1989]
 SYNONYMS                 BW-248U [Merck Index 1989]
 SYNONYMS                 Zovirax [USAN 1995]
 SYNONYMS                 9-((2-hydroxyethoxy)methyl)guanine [Merck
                          Index 1989]
 SYNONYMS                 Vipral [Merck Index 1989]
 SYNONYMS                 Virorax [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 010
 PROTOCOL ID NUMBERS      NIAID ACTG 063
 PROTOCOL ID NUMBERS      NIAID ACTG 070
 PROTOCOL ID NUMBERS      NIAID ACTG 095
 PROTOCOL ID NUMBERS      FDA 018A
 PROTOCOL ID NUMBERS      FDA 033A
 PROTOCOL ID NUMBERS      FDA 104A
 PROTOCOL ID NUMBERS      NCI 89 C-89
 PROTOCOL ID NUMBERS      NIAID ACTG 169
 PROTOCOL ID NUMBERS      FDA 104B
 PROTOCOL ID NUMBERS      FDA 130A
 PROTOCOL ID NUMBERS      NIAID ACTG 204
 IND NUMBER               30,005
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Converted to acyclovir
                          monophosphate, a nucleotide analogue, by
                          Herpes simplex virus-coded thymidine kinase;
                          the monophosphate is converted to diphosphate
                          by cellular guanylate kinase, and into
                          triphosphate by various cellular enzymes; the
                          triphosphate interferes with Herpes simplex
                          virus DNA polymerase and inhibits DNA
                          replication. Dose-independent
                          pharmacokinetics were observed in intravenous
                          doses of 0.5-15 mg/kg; dose-dependent plasma
                          levels were found after single doses or a
                          steady state after multiple doses; for 1-hour
                          infusions of 250 mg/square meter every 8
                          hours, mean steady-state peak and trough
                          plasma levels were 9.8 and 0.7 mcg/ml,
                          respectively. Acyclovir appears to distribute
                          into all tissues, especially renal tissue,
                          and is poorly protein bound (9-33 percent).
                          Renal excretion is a major route of
                          elimination in subjects with normal renal
                          function, via glomerular filtration and
                          tubular secretion, accounting for 62-91
                          percent of total body clearance. [PDR 1995]
 DISEASES STUDIED/TREATED Initial treatment and management of recurrent
                          herpes virus (genitalis; simplex; zoster)
                          infections and chickenpox infections in
                          immunocompromised patients [PDR 1995]
 CLASSIFICATION CODE      Antiviral [USAN 1995]
 OTHER MAJOR USES         Initial treatment and management of recurrent
                          herpes virus (genitalis; simplex; zoster)
                          infections in nonimmunocompromised patients
                          [PDR 1995]
 SUBSTANCE INTERACTIONS   Adminstration of nephrotoxic drugs with
                          intravenous acyclovir may increase the
                          potential for nephrotoxicity, especially in
                          patients with renal function impairment.
                          Probenecid may decrease tubular excretion of
                          intravenous acyclovir producing increased
                          acyclovir serum or cerebral spinal fluid
                          concentrations, and possible increased
                          toxicity. [USP DI 1995]
 ADVERSE EFFECTS          Most frequent adverse effect reported is
                          inflammation or phlebitis at the injection
                          site, transient elevations of serum
                          creatinine, and rash or hives.  Less frequent
                          adverse reactions were hematuria, diaphoresis
                          and increased blood urea nitrogen in patients
                          with impaired renal function.  May cause
                          nausea and/or vomiting. [PDR 1995]
 CONTRAINDICATIONS        Should not be used by patients who develop
                          hypersensitivity or intolerance. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthetic acyclic purine
                          nucleoside analogue [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C8H11N5O3 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 225.21 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C42.66%;
                          H4.92%; N31.10%; O21.31% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: In water: Acyclovir has a maximum
                          solubility in water of 2.5mg/ml at 37C; the
                          sodium salt has a solubility in water
                          exceeding 100 mg/ml. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White crystalline
                          powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 256.5-257 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: After reconstitution with sterile
                          water for injection solutions at
                          concentrations of 50 mg/ml retain their
                          potency for 12 hours at 15 to 25 C. [USP DI
                          1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Solutions for intravenous infusion
                          diluted with electrolytes or dextrose retain
                          their potency for 24 hours at 15 to 25 C.
                          [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Refrigeration of reconstituted
                          solutions may produce a precipitate which can
                          be redissolved by warming to room
                          temperature. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Sterile powder for intravenous
                          infusion (500 mg/vial); ointment (5 percent
                          formulation); 200 mg capsules; 800 mg
                          tablets; and banana-flavored syrup containing
                          200 mg/tsp. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion;
                          topical application; oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 15-25 C (59-77 F), and
                          protect from light. [PDR 1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Stein DS, Graham NM, Park LP, Hoowver DR,
                          Phair JP, Detels R, Ho M, Saah AJ. The effect
                          of the interaction of acyclovir with
                          zidovudine on progression to AIDS and
                          survival. Ann Intern Med. 1994 Jul
                          15;121(2):100-8.
 REFERENCES               Youle MS, Gazzard BG, Johnson MA, Cooper DA,
                          Hoy JF, Busch H, Ruf B, Griffiths PD,
                          Stephenson SL, Dancox M, et al. Effects of
                          high-dose oral acyclovir on herpesvirus
                          disease and survival in patients with
                          advanced HIV disease: a double-blind,
                          placebo-controlled study. European-Australian
                          Acyclovir Study Group [published erratum
                          appears in AIDS 1994 Jun;8(6):following 859].
                          AIDS. 1994 May;8(5):641-9.
 REFERENCES               Lyall EG, Ogilvie MM, Smith NM, Burns S.
                          Acyclovir resistant varicella zoster and HIV
                          infection. Arch Dis Child. 1994
                          Feb;70(2):133-5.
 REFERENCES               Jahn S, Busch HW, Reichelt D, Christensen S,
                          Zidek W. Zidovudine or zidovudine/acyclovir
                          in patients with asymptomatic HIV infection
                          and CD4+ cell counts greater than 400/microL.
                          Int Conf AIDS. 1994 Aug 7-12;10(1):213
                          (abstract no. PBO280).
 REFERENCES               Shavdia N, Sharvadze L, Tsertsvadze T,
                          Medulashvili G, Aladashvili M, Chubinishvili
                          O. The comparative efficacy of acyclovir,
                          isoprinosine and their combination in
                          patients with herpes simplex. Int Conf AIDS.
                          1993 Jun 6-11;9(1):354 (abstract no.
                          PO-BO8-1313).
 REFERENCES               Cooper DA, Pehrson PO, Pedersen C, Moroni M,
                          Oksenhendler E, Rozenbaum W, Clumeck N, Faber
                          V, Stille W, Hirschel B, et al. The efficacy
                          and safety of zidovudine alone or as
                          cotherapy with acyclovir for the treatment of
                          patients with AIDS and AIDS-related complex:
                          a double-blind randomized trial. AIDS. 1993
                          Feb;7(2):197-207.
 REFERENCES               Safrin S. Treatment of acyclovir-resistant
                          herpes simplex virus infections in patients
                          with AIDS. J Acquir Immune Defic Syndr.
                          1992;5 Suppl 1:S29-32.
 REFERENCES               Lavelle J, Lang W, Lefkowitz L, Peterson E,
                          Saag M, Spruance S, Greenberg S, Kessler H. A
                          randomized trial comparing zidovudine alone
                          and in combination with acyclovir for
                          treatment of early symptomatic HIV infection.
                          Int Conf AIDS. 1992 Jul 19-24;8(2):B184
                          (abstract no. PoB 3585).
 REFERENCES               Safrin S, Elbaggari A, Elbeik T. Risk factors
                          for the development of acyclovir-resistant
                          herpes simplex virus (HSV) infection. Int
                          Conf AIDS. 1992 Jul 19-24;8(1):Th75 (abstract
                          no. ThB 1548).
 REFERENCES               Bary M, Vittecoq D, Rouzioux C, Back JF.
                          Incidence and predictive value of CMV
                          viraemia in AIDS patients without clinical
                          evidence of CMV infection treated by
                          zidovudine (ZDV) with or without acyclovir
                          (ACV). Int Conf AIDS. 1992 Jul
                          19-24;8(2):B185 (abstract no. PoB 3590).
 ENTRY MONTH              8906
 LAST REVISION DATE       960612
 

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