Valacyclovir (Valtrex) versus ...

Valacyclovir vs. Acyclovir (Zovirax)

Difference between Valacyclovir and Acyclovir chart:

Drug class
Antiviral, Acyclic nucleoside analog
Mechanism of action
Work as DNA polymerase inhibitors, thereby reducing DNA synthesis and viral replication.
Chemical structure Structurally, valacyclovir differs from acyclovir by the presence of the amino acid valine attached to the 5-hydroxyl group of the nucleoside
Preparations Oral Oral,
Common FDA approved indications
Management of recurrent episodes of genital herpes
Treatment of initial episodes of genital herpes
Treatment of chickenpox (varicella)
Treatment of herpes zoster (shingles)
Other FDA-approved indications Chronic suppressive therapy of recurrent episodes of genital herpes
Reduction of transmission of genital herpes
Treatment of cold sores
Herpes Simplex Encephalitis (acyclovir injection only)
Neonatal HSV infection (acyclovir injection only)
Recurrent cold sores (topical only)
Low, 10-20%
Absorption Increased GI absorption Poorly absorbed from the GI tract
about 3 hours
about 3 hours
Excellent safety profiles
Dehydration and preexisting renal dysfunction may predispose to the development of renal impairment and neurotoxicity

Acyclovir itself is poorly absorbed in the gastrointestinal tract -- its oral bioavailability is 10% - 30%. In contrast, valacyclovir is more than 10 times more permeable than acyclovir. Valacyclovir's oral bioavailability is more than 55%, which allows comparable blood levels to parenteral acyclovir.

The main advantage of valacyclovir over acyclovir is convenience of less frequent dosing regimen. But it is quite more expensive than acyclovir.

Recurrent genital herpes

The study has demonstrated that valacyclovir 500 mg twice daily is equivalent in efficacy to acyclovir 200 mg five times daily as episodic treatment of recurrent genital HSV infection. Valacyclovir maintains the established efficacy and safety of acyclovir but offers a much more convenient dosing regimen 1.

First-episode genital herpes

Valacyclovir is as effective and well tolerated in the treatment of first-episode genital herpes as acyclovir. Valacyclovir provides a useful alternative to acyclovir with the advantage of a more convenient dosing regimen and the potential for better compliance2.

Suppression of HSV shedding

Although the suppression of viral replication is not complete, valacyclovir and acyclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding. No significant differences in frequency and quantity of HSV were detected by polymerase chain reaction (PCR) between the valacyclovir and acyclovir 3.

Herpes zoster

Valacyclovir is superior to acyclovir in the treatment of herpes zoster. While both medications significantly shorten the periods of acute pain, time to complete zoster rash crusting and resolution, valaciclovir significantly accelerate the resolution of herpes zoster-associated pain compared with acyclovir5.

Clinical studies5, 9 have shown an average reduction of the duration of pain from 60 days, as seen with acyclovir, to 40 days with valacyclovir. Reductions in pain were also noted at 6 months after healing of the rash, as only 19% of patients taking valacyclovir reported pain, compared to the 26% of patients taking acyclovir.

Recurrent herpes simplex virus eye disease

One-year suppression therapy with oral valacyclovir (500 mg tablet daily) is as effective and as well tolerated as acyclovir (400 mg tablet twice daily) in reducing the rate of recurrent ocular HSV disease8.

Post-transplantation cytomegalovirus prophylaxis

Valacyclovir appears to be more effective than acyclovir in preventing CMV reactivation in bone marrow transplant recipients. 4

Valacyclovir vs. Famciclovir (Famvir)

Famciclovir has superior bioavailability (about 75%) compared to both acyclovir and valacyclovir.

Herpes zoster

Valacyclovir is comparable to famciclovir in speeding the resolution of zoster-associated pain and postherpetic neuralgia. Safety profiles for valacyclovir and famciclovir are similar, with headache and nausea the most common adverse events 7.

Recent Japanese study10 found that famciclovir provides significantly earlier reduction of acute pain in herpes zoster than valacyclovir.

Genital herpes

Valacyclovir appears to be somewhat better than famciclovir for suppression of genital herpes and associated shedding. 6.


Further reading

  • 1. 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
  • 2. Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth R. 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 Virus Study Group. Sex Transm Dis. 1997 Sep;24(8):481-6. PubMed
  • 3. 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. PubMed
  • 4. Ljungman P, de La Camara R, Milpied N, Volin L, Russell CA, Crisp A, Webster A; Valacyclovir International Bone Marrow Transplant Study Group. Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Blood. 2002 Apr 15;99(8):3050-6. PubMed
  • 5. Lin WR, Lin HH, Lee SS, Tsai HC, Huang CK, Wann SR, Chen YS, Chiang SC, Yen MY, Liu YC. Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster. J Microbiol Immunol Infect. 2001 Jun;34(2):138-42. PubMed
  • 6. Wald A, Selke S, Warren T, Aoki FY, Sacks S, Diaz-Mitoma F, Corey L. Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. Sex Transm Dis. 2006 Sep;33(9):529-33. PubMed
  • 7. Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. 2000 Sep-Oct;9(9):863-9. PubMed
  • 8. Miserocchi E, Modorati G, Galli L, Rama P. Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. Am J Ophthalmol. 2007 Oct;144(4):547-51. PubMed
  • 9. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995;39:1546–53.
  • 10. Ono F, Yasumoto S, Furumura M, Hamada T, et al. Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster. J Dermatol. 2012 Nov;39(11) PubMed

Published: March 31, 2008
Last updated: August 10, 2014


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