Acyclovir (Zovirax®) vs Valacyclovir (Valtrex®)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Difference between Acyclovir and Valacyclovir

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

Acyclovir vs Valacyclovir infographic

Comparative chart:

Acyclovir Valacyclovir
• Zovirax®
• Valtrex®
Zovirax cream 5% Valtrex tablets
Drug class
• Antiviral, Synthetic nucleoside analogue
Chemical structure
• Structurally, valacyclovir differs from acyclovir by the presence of the amino acid valine attached to the 5-hydroxyl group of the nucleoside
Dose formulations
• Oral tablets
• Oral capsules
• Oral suspension
• Topical cream 5%
• Intravenous
• Oral tablets
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)
• Herpes Simplex Encephalitis (acyclovir injection only)
• Neonatal HSV infection (acyclovir injection only)
• Recurrent cold sores (topical only)
• Chronic suppressive therapy of recurrent episodes of genital herpes
• Reduction of transmission of genital herpes
• Treatment of cold sores
Off-Label uses
• Herpes zoster ophthalmicus6
• Low, 10-20%,
decreases with higher doses
• 55%
• Poorly absorbed from the GI tract • Increased GI absorption
• 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.
• ~ 3 hours • ~ 3 hours
• Hypersensitivity to acyclovir, valacyclovir or any component of the formulation
Toxicity, Side effects
• Excellent safety profiles
• Dehydration and preexisting renal dysfunction may predispose to the development of renal impairment and neurotoxicity
Pregnancy category
• B


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 simple dosing regimen and the potential for better compliance2. But acyclovir is much less expensive.

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.

Acyclovir and valacyclovir are equally effective as prophylactic therapy for herpes zoster. However, the cost of acyclovir prophylaxis is considerably lower10.

Recurrent herpes simplex virus eye disease

One-year suppressive 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

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. 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
  • 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. Usami E, Kimura M, Iwai M, Teramachi H, Yoshimura T. Prophylactic Efficacy Against Herpes Zoster and Costs Difference Between Acyclovir and Valaciclovir in Hematological Patients. In Vivo. 2016 09-10;30(5):701-5. PubMed

Published: December 20, 2016
Last updated: November 07, 2018


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