Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Valacyclovir: An overview

INTRODUCTION

Valacyclovir  is the valyl ester of the antiviral drug acyclovir [1]. Acting as an oral prodrug, valacyclovir is converted in vivo to acyclovir. Acyclovir, a nucleoside analog, is phosphorylated by virally-encoded thymidine kinase and subsequently by cellular enzymes, yielding acyclovir triphosphate, which competitively inhibits viral DNA polymerase. (See "Acyclovir: An overview".)

BASIC PHARMACOKINETICS

The antiviral activity of valacyclovir reflects its in vivo conversion to acyclovir, which is active against herpes simplex viruses types 1 and 2, varicella zoster virus, and Epstein-Barr virus. Cytomegalovirus (CMV), which does not encode thymidine kinase, is resistant at clinically achievable oral doses [2,3]. However, high-dose intravenous acyclovir (10 mg/kg every eight hours) can achieve drug levels sufficient to suppress CMV [4].

The mechanism of resistance to valacyclovir is identical to that described for acyclovir. Three mechanisms have been shown to endow herpes simplex viruses with resistance to acyclovir, a phenomenon rare in the immunocompetent host [5]:

  • Reduced or absent thymidine kinase
  • Altered thymidine kinase activity resulting in decreased acyclovir phosphorylation
  • Altered viral DNA polymerase with decreased affinity for acyclovir triphosphate

(See "Acyclovir: An overview", section on 'Mechanism of resistance'.)
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. Valtrex (valacyclovir hydrochloride) Product Information, Glaxo Wellcome Inc, 1996.
  2. Albriah, FA, Sacks, SL. New antiherpesvirus agents: Their targets and therapeutic potential. Drugs 1996; 52:17.
  3. Perry, CM, Faulds, D. Valaciclovir: A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections. Drugs 1996; 52:754.
  4. Cole, NL, Balfour, HH Jr. In vitro susceptibility of cytomegalovirus isolates from immunocompromised patients to acyclovir and ganciclovir. Diagn Microbiol Infect Dis 1987; 6:255.
  5. Chatis, PA, Crumpacker, CS. Minireview: Resistance of herpes viruses to antiviral drugs. Antimicrob Agents Chemother 1992; 36:1589.
  6. Feinberg, JE, Hurwitz, S, Cooper, D, et al. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. J Infect Dis 1998; 177:48.
  7. Bell, WR, Chulay, JD, Feinberg, JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore) 1997; 76:369.
  8. Beutner, KR, Friedman, DJ, Forszpaniak, C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39:1546.
  9. Bryson, YJ, Dillon, M, Lovett, M, et al. Treatment of first episodes of genital herpes simplex virus with oral acyclovir. N Engl J Med 1983; 308:916.
  10. Fife, KH, Barbarash, RA, Rudolph, T, et al. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Study Group. Sex Transm Dis 1997; 24:481.
  11. Reichman, RC, Badger, GJ, Mertz, GJ, et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir. JAMA 1984; 251:2103.
  12. Spruance, SL, Tyring, SK, DeGregorio, B, et al. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis: Valaciclovir HSV Study Group. Arch Intern Med 1996; 156:1729.
  13. Bodsworth, NJ, Crooks, RJ, Borelli, S, et al. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: A randomised, double blind clinical trial: International Valaciclovir HSV Study Group. Genitourin Med 1997; 73:110.
  14. Douglas, JM, Critchlow, C, Benedetti, J, et al. A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med 1984; 310:1551.
  15. Patel, R, Bodsworth, NJ, Woolley, P, et al. Valaciclovir for the suppression of recurrent genital HSV infection: A placebo controlled study of once daily therapy: International Valaciclovir HSV Study Group. Genitourin Med 1997; 73:105.
white circle LOG IN
white circle DEMO