Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Acyclovir: An overview

INTRODUCTION

Acyclovir is widely used in the treatment of herpesvirus infections, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). An overview of the mechanisms of action of and resistance to acyclovir and its major clinical uses will be provided here.

Dosing and treatment of the specific clinical syndromes are described in greater detail on the appropriate topic reviews.

Use of valacyclovir or famciclovir, which are later generation agents with a similar mechanism of action, are discussed elsewhere. (See "Valacyclovir: An overview" and "Famciclovir: An overview".)

MECHANISM OF ACTION

Acyclovir (9-[2-hydroxymethyl]guanine) is a nucleoside analog that selectively inhibits the replication of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV). After intracellular uptake, it is converted to acyclovir monophosphate by virally-encoded thymidine kinase. This step does not occur to any significant degree in uninfected cells and thereby lends specificity to the drug's activity. The monophosphate derivative is subsequently converted to acyclovir triphosphate by cellular enzymes.

Acyclovir triphosphate competitively inhibits viral DNA polymerase by acting as an analog to deoxyguanosine triphosphate (dGTP). Incorporation of acyclovir triphosphate into DNA results in chain termination since the absence of a 3' hydroxyl group prevents the attachment of additional nucleosides. Acyclovir triphosphate has a much higher affinity for viral DNA polymerase than for the cellular homolog, yielding a high therapeutic ratio [1,2].

            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2014. | This topic last updated: Jul 8, 2014.
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 ©2014 UpToDate, Inc.
References
Top
  1. Whitley RJ, Gnann JW Jr. Acyclovir: a decade later. N Engl J Med 1992; 327:782.
  2. Hirsch MS, Swartz MN. Drug therapy: antiviral agents (second of two parts). N Engl J Med 1980; 302:949.
  3. Chatis PA, Crumpacker CS. Resistance of herpesviruses to antiviral drugs. Antimicrob Agents Chemother 1992; 36:1589.
  4. Levin MJ, Bacon TH, Leary JJ. Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients. Clin Infect Dis 2004; 39 Suppl 5:S248.
  5. Englund JA, Zimmerman ME, Swierkosz EM, et al. Herpes simplex virus resistant to acyclovir. A study in a tertiary care center. Ann Intern Med 1990; 112:416.
  6. Erlich KS, Mills J, Chatis P, et al. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320:293.
  7. Hardy WD. Foscarnet treatment of acyclovir-resistant herpes simplex virus infection in patients with acquired immunodeficiency syndrome: preliminary results of a controlled, randomized, regimen-comparative trial. Am J Med 1992; 92:30S.
  8. Boivin G, Edelman CK, Pedneault L, et al. Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS. J Infect Dis 1994; 170:68.
  9. Laskin OL. Clinical pharmacokinetics of acyclovir. Clin Pharmacokinet 1983; 8:187.
  10. Adair JC, Gold M, Bond RE. Acyclovir neurotoxicity: clinical experience and review of the literature. South Med J 1994; 87:1227.
  11. Drugs for non-HIV viral infections. Treat Guidel Med Lett 2007; 5:59.
  12. Sawyer MH, Webb DE, Balow JE, Straus SE. Acyclovir-induced renal failure. Clinical course and histology. Am J Med 1988; 84:1067.
  13. Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci 2003; 325:349.
  14. Feldman S, Rodman J, Gregory B. Excessive serum concentrations of acyclovir and neurotoxicity. J Infect Dis 1988; 157:385.
  15. Davenport A, Goel S, Mackenzie JC. Neurotoxicity of acyclovir in patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1992; 20:647.
  16. Stathoulopoulou F, Almond MK, Dhillon S, Raftery MJ. Clinical pharmacokinetics of oral acyclovir in patients on continuous ambulatory peritoneal dialysis. Nephron 1996; 74:337.
  17. Almond MK, Fan S, Dhillon S, et al. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron 1995; 69:428.
  18. Pasternak B, Hviid A. Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. JAMA 2010; 304:859.
  19. pregnancyregistry.gsk.com/acyclovir.html (Accessed on September 25, 2012).
  20. American Academy of Pediatrics. Red Book Online News. Shortage of intravenous acyclovir. http://aapredbook.aappublications.org/site/news#76 (Accessed on December 04, 2012).
  21. US Food and Drug Administration. Current Drug Shortages. http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm314739.htm (Accessed on December 04, 2012).
  22. American Academy of Pediatrics. Red Book Online. Antiviral recommendations for herpes simplex virus (HSV) and varicella zoster virus (vzv) infections in hospitalized pediatric patients during the intravenous acyclovir shortage. http://aapredbook.aappublications.org/site/news/acyclovir.xhtml (Accessed on December 04, 2012).