eMedExpert Home > Medications Facts > Acyclovir (Zovirax)

Acyclovir was the first successful anti-viral medicationt in the world. It was originally synthesized in 1974 by Howard Schaeffer at Wellcome Research Laboratories (now GlaxoSmithKline). After Schaeffer's discovery, Gertrude B. Elion and her team went to work, studying how it worked, why it worked, and why it was so nontoxic. They discovered that acyclovir remains inert until it meets the herpes virus.

For four years, from 1974 to 1977, more than seventy-five researchers kept acyclovir secret. The first report detailing the selective antiviral activity of acyclovir against herpes viruses was published in 1977 2.

The drug got FDA approval and was released commercially in 1982. It was marked under the trade name Zovirax by the Burroughs Wellcome Company. The original formulation was a topical ointment. Acyclovir became available in oral formulation (200 mg capsules) in 1985 20.

• Oral
• Initial genital herpes
• Recurrent genital herpes
• Herpes zoster infections (shingles)
• Chickenpox (varicella)
• Topical
• Recurrent herpes labialis (cold sores)
• Parenteral
• Herpes simplex, mucosal and cutaneous
• Severe initial episodes of genital herpes
• Herpes simplex encephalitis
• Neonatal herpes simplex infection
• Varicella-zoster (shingles) infections

• Prevention of HSV-2 transmission 16
• Cytomegalovirus infection and disease after organ transplantation 6, 9
• Herpes simplex virus infection after organ transplantation 13, 21, 22
• Ocular herpes simplex 10, 11, 15
• Herpes zoster ophthalmicus 17
• Varicella pneumonia18
• Infectious mononucleosis 4

Acyclovir boasts activity against four of the five major herpes-group viruses:

• Herpes simplex virus type 1 (HSV-1) 7
• Herpes simplex virus type 2 (HSV-2) 7
• Varicella zoster virus (VZV) 7
• Epstein-Barr virus (EBV)5, 7
• Cytomegalovirus (CMV) (poor activity) 7, 8

• Advantages:
• high efficacy against HSV and VZV infections
• excellent clinical safety record (favorable safety profile) 23
• well-tolerated by most patients
• highly effective for suppression of HSV shedding 14, 16
• considered safe for the mother and baby during pregnancy (so far, no adverse outcomes in the fetus or newborn have been reported)
• minor risk of drug interactions
• inexpensive
• Disadvantages:
• low bioavailability
• inconvenient frequent dosing regimen 12
• risk of renal failure and neurotoxicity 19
• does not eradicate latent virus

Acyclovir is a synthetic purine nucleoside analogue with inhibitory activity against herpes simplex virus types 1, 2, and varicella-zoster virus. The inhibitory activity of Acyclovir is highly selective. Acyclovir is converted to acyclovir monophosphate by virus-specific enzymes thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes.

Acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of Acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.

Acyclovir has a short half-life about 2.5 to 3.3 hr

• Acyclovir (Zovirax) versus Other Medications

• 1. Physicians’ Desk Reference, 54th ed; Medical Economics, Thomson Healthcare: Montvale, NJ; 2000.
• 2. Elion, G. B., P. A. Furman, J. A. Fyfe, P. de Miranda, L. Beauchamp, and H. J. Shaeffer. 1977. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. USA 74:5716-5720.
• 3. Darby, G. 1995. In search of the perfect antiviral. Antiviral Chem. Chemother. 6(Suppl. 1):54-63.
• 4. Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother. 1983 Sep;12 Suppl B:113-21.
• 5. Datta AK, Colby BM, Shaw JE, Pagano JS. Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5163-6.
• 6. Gavalda J, de Otero J, Murio E, Vargas V, Rossello J, Calico I, Margarit C, Pahissa A. Two grams daily of oral acyclovir reduces the incidence of cytomegalovirus disease in CMV-seropositive liver transplant recipients. Transpl Int. 1997;10(6):462-5. PubMed
• 7. Collins P. The spectrum of antiviral activities of acyclovir in vitro and in vivo. J Antimicrob Chemother. 1983 Sep;12 Suppl B:19-27.
• 8. Freitas VR, Smee DF, Chernow M, Boehme R, Matthews TR. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses. Antimicrob Agents Chemother. 1985 Aug;28(2):240-5.
• 9. Legendre C, Ducloux D, Ferroni A, Chkoff N, Geffrier C, Rouzioux C, Kreis H. Acyclovir in preventing cytomegalovirus infection in kidney transplant recipients: a case-controlled study. J Med Virol. 1993;Suppl 1:118-22. PubMed
• 10. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300-6.
• 11. Uchoa UB, Rezende RA, Carrasco MA, Rapuano CJ, Laibson PR, Cohen EJ. Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection. Arch Ophthalmol. 2003 Dec;121(12):1702-4. Pubmed
• 12. Bodsworth NJ, Crooks RJ, Borelli S, Vejlsgaard G, Paavonen J, Worm AM, Uexkull N, Esmann J, Strand A, Ingamells AJ, Gibb A. 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 Apr;73(2):110-6. PubMed
• 13. Eisen D, Essell J, Broun ER, Sigmund D, DeVoe M. Clinical utility of oral valacyclovir compared with oral acyclovir for the prevention of herpes simplex virus mucositis following autologous bone marrow transplantation or stem cell rescue therapy. Bone Marrow Transplant. 2003 Jan;31(1):51-5.
• 14. Gupta R, Wald A, Krantz E, Selke S, Warren T, Vargas-Cortes M, Miller G, Corey L. Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract. J Infect Dis. 2004 Oct 15;190(8):1374-81. Epub 2004 Sep 20. PubMed
• 15. Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000 Aug;118(8):1030-6. PubMed
• 16. Wald A, Zeh J, Barnum G, Davis LG, Corey L. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):8-15. PubMed
• 17. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology. 2000 Aug;107(8):1507-11. PubMed
• 18. El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis. 1998 Jan-Mar;2(3):147-51. PubMed
• 19. Johnson GL, Limon L, Trikha G, Wall H. Acute renal failure and neurotoxicity following oral acyclovir. Ann Pharmacother. 1994 Apr;28(4):460-3. PubMed
• 20. FDA Center for Drug Evaluation and Research. Drug Details for Zovirax.
• 21. Pettersson E, Eklund B, Ho"ckerstedt K, Salmela K, Ahonen J. Acyclovir and renal transplantation. Scand J Infect Dis Suppl. 1985;47:145-8. PubMed
• 22. Carrier M, Pelletier GB, Cartier R, Leclerc Y, Pelletier LC. Prevention of herpes simplex virus infection by oral acyclovir after cardiac transplantation. Can J Surg. 1992 Oct;35(5):513-6. PubMed
• 23. Tilson HH, Engle CR, Andrews EB. Safety of acyclovir: a summary of the first 10 years experience. J Med Virol. 1993;Suppl 1:67-73. PubMed

Published: March 31, 2008
Last updated: January 07, 2010