      Document 0128
 DOCN  DRG0128
 UNIQUE IDENTIFIER        DRG-0119
 NAME OF SUBSTANCE        Valacyclovir hydrochloride [USAN 1996]
 REGISTRY NUMBER          124832-27-5
 STANDARD CHEMICAL NAME   L-Valine,
                          2-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)m-
                          ethoxy)-ethyl ester, monohydrochloride [USAN
                          1996]
 SYNONYMS                 Valtrex [USAN 1996]
 SYNONYMS                 Valaciclovir hydrochloride [USAN 1996]
 PROTOCOL ID NUMBERS      FDA 104A
 PROTOCOL ID NUMBERS      FDA 104B
 PROTOCOL ID NUMBERS      NIAID ACTG 204
 PROTOCOL ID NUMBERS      NIAID ACTG 253
 SECONDARY SOURCE ID      BW256U87 [AmFAR Tx Dir 1995;7(4)]
 SECONDARY SOURCE ID      256U87 [Int Conf AIDS 1992 Jul 19-24;8(2)
                          abstract PoB 3885]
 SECONDARY SOURCE ID      BW 256U87 [NIAID ACTG 204]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Valacyclovir is rapidly and
                          extensively converted to acyclovir by first
                          pass metabolism after oral administration.
                          After 3 hours postdosing, valacyclovir was
                          not detectable in plasma. Acyclovir was
                          measurable in plasma as early as 15 minutes
                          following valacyclovir dosing and plasma
                          concentrations of acyclovir greatly exceeded
                          those of valacyclovir. The time to maximum
                          concentration in serum and half-life of
                          acyclovir after valacyclovir administration
                          were about 2 and 3 hours, respectively.
                          [Antimicrob Agents Chemother 1994 Jul;38(7)]
 DISEASES STUDIED/TREATED Herpes simplex [NIAID ACTG 253]
 DISEASES STUDIED/TREATED Varicella ( chickenpox ) [NIAID ACTG 253]
 DISEASES STUDIED/TREATED Herpes zoster ( shingles ) [NIAID ACTG 253]
 DISEASES STUDIED/TREATED WARNING: NOT INDICATED IN TREATMENT OF
                          IMMUNOCOMPROMISED PATIENTS (e.g., those with
                          advanced HIV disease, defined as CD4 count <
                          50 cells/mm3) [Burroughs Wellcome fact sheet
                          June 1995]
 CLASSIFICATION CODE      Antiviral [USAN 1996]
 OTHER MAJOR USES         Varicella zoster virus, herpes zoster
                          (shingles) therapy. Per June 1995 Burroughs
                          Wellcome Fact Sheet: valacyclovir HCl is only
                          indicated for treatment of herpes zoster in
                          immunocompetent adults [Med Care 1995
                          Apr;33(4 Suppl)] [Drugs 1994 Oct;48(4)]
                          [Burroughs Wellcome fact sheet June 1995]
 SUBSTANCE INTERACTIONS   May work synergistically with AZT. [AmFAR Tx
                          Dir 1993;6(4)]
 ADVERSE EFFECTS          WARNING: THROMBOTIC THROMBOCYTOPENIC PURPURA
                          / HEMOLYTIC UREMIC SYNDROME ( TTP / HUS ), in
                          some cases resulting in death, has been
                          reported in patients with ADVANCED HIV
                          DISEASE (CD4 count < 50 cells/mm3) and also
                          in bone marrow transplant and renal
                          transplant patients in clinical trials. The
                          most common adverse effects of valacyclovir
                          HCl were nausea, headache, vomiting,
                          diarrhea, constipation, asthenia, dizziness,
                          abdominal pain, and anorexia. [Antimicrob
                          Agents Chemother 1994 Jul;38(7)] [Burroughs
                          Wellcome fact sheet June 1995]
 CONTRAINDICATIONS        Contraindicated in patients with advanced HIV
                          disease and with known hypersensitivity or
                          intolerance to valacyclovir, acyclovir, or
                          any component of the formulation. [Burroughs
                          Wellcome fact sheet June 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The L-valyl ester of
                          acyclovir as the HCl salt [Antimicrob Agents
                          Chemother 1994 July;38(7)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C13H20N6O4.HCl [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 360.80 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white
                          powder [Burroughs Wellcome fact sheet June
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [AmFAR Tx Dir
                          1995;7(4)] [Antimicrob Agents Chemother 1994
                          Jul;38(7)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules; 500 mg caplets.
                          [Antimicrob Agents Chemother 1994 Jul;38(7)]
                          [Burroughs Wellcome fact sheet June 1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               James JS. Valacyclovir study stopped -- worse
                          survival. AIDS Treat News. 1995 Feb 17;(no
                          217):7-8.
 REFERENCES               Bentley S, Soul-Lawton J, Rolan P. Absolute
                          bioavailability of acyclovir is substantially
                          increased following oral valaciclovir
                          (Valtrex). Int Conf AIDS. 1994 Aug
                          7-12;10(2):127 (abstract no. PB0523).
 REFERENCES               Mills J. Prophylaxis and treatment of
                          opportunistic viral infections in patients
                          with HIV infection. Annu Conf Australas Soc
                          HIV Med. 1994 3-6;6:134 (unnumbered
                          abstract).
 REFERENCES               Jacobson MA, Gallant J, Wang LH, Coakley D,
                          Weller S, Gary D, Squires L, Smiley ML, Blum
                          MR, Feinberg J. Phase I trial of
                          valaciclovir, the L-valyl ester of acyclovir,
                          in patients with advanced human
                          immunodeficiency virus disease. Antimicrob
                          Agents Chemother. 1994 Jul;38j(7):1534-40.
 REFERENCES               Weller S, Blum MR, Doucette M, Burnette T, et
                          al. Pharmacokinetics of the acyclovir
                          pro-drug valaciclovir after escalating
                          single- and multiple-dose administration to
                          normal volunteers. Clin Pharmacol Ther. 1993
                          Dec;54(6):595-605.
 REFERENCES               Jacobson MA. Valaciclovir (BW256U87): the
                          L-valyl ester of acyclovir. J Med Virol.
                          1993;Suppl 1:150-3.
 REFERENCES               Puripoy DJ, Beauchamp LM, de Miranda P, Ertl
                          P, et al. Review of research leading to new
                          anti-herpesvirus agents in clinical
                          development: valaciclovir hydrochloride
                          (256U, the L-valyl ester of acyclovir) and
                          882C, a specific agent for varicella zoster
                          virus. J Med Virol. 1993;Suppl 1:139-45.
 REFERENCES               Feinberg J, Gallant J, Weller S, Coakley D,
                          Gary D, Squires L, Smiley ML, Blum MR,
                          Jacobson M. A phase I evaluation of 256U87,
                          an acyclovir (ACV) prodrug, in HIV infected
                          patients. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B238 (abstract no. PoB 3885).
 ENTRY MONTH              9108
 LAST REVISION DATE       960612
 

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