American Journal of Clinical Dermatology

, Volume 3, Issue 9, pp 591–598 | Cite as

Oral Antivirals Revisited in the Treatment of Herpes Zoster

What Do They Accomplish?
  • Arjen F. Nikkels
  • Gérald E. Piérard
Current Opinion


Oral antiviral agents currently represent the most important therapeutic keystone in the treatment of herpes zoster. Three oral antiviral agents are available for the treatment of herpes zoster: acyclovir, its derivative valacyclovir, and famciclovir. Meta-analysis of published data has shown that oral acyclovir significantly reduces various herpes zoster-related symptoms as well as the duration, intensity and prevalence of zoster-associated pain (ZAP). However, this drug does not influence postherpetic neuralgia. The newer agents famciclovir and valacyclovir exhibit a better oral bioavailability than acyclovir. These agents have demonstrated similar efficacy to acyclovir with ZAP and they require less frequent administration.

When initiated within 72 hours, oral antiviral therapy of herpes zoster is beneficial in selected, elderly immunocompetent patients, reducing the duration and intensity of ZAP and providing more rapid skin lesion healing. Oral antivirals are also of benefit in immunocompromised patients with uncomplicated herpes zoster. However, signs of cutaneous and visceral dissemination should be monitored; if signs occur, intravenous antiviral therapy is indicated.


Herpes Zoster Acyclovir Varicella Zoster Virus Famciclovir Varicella Zoster Virus Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.


  1. 1.
    Grose C. Varicella zoster virus infections: chickenpox, shingles, and varicella vaccine. In: Glaser R., Jones J.F., editors. Herpes virus infection. New York: Marcel Dekker Inc, 1994: 1117–85Google Scholar
  2. 2.
    Arvin A.M. Varicella zoster virus. In: Fields B.N., Knipe D.M., Howley P.M., et al., editors. Fields virology. 3rd ed. Philadelphia (PA): Lippincott-Publishers, 1996: 2547–85Google Scholar
  3. 3.
    Sanders H.W.A. Herpes zoster in de huisartspraktijk [doctoral thesis]. Nijmegen: University of Nijmegen, 1968Google Scholar
  4. 4.
    Dworkin R.H., Perkins F.M., Nagasako E.M. Prospects for the prevention of postherpetic neuralgia in herpes zoster patients. Clin J Pain 2000; 16 (2 Suppl.): S90–100PubMedCrossRefGoogle Scholar
  5. 5.
    Levin M.J. Vaccination against zoster. Pain Res Clin Manag 2001; 11: 131–42Google Scholar
  6. 6.
    Petursson G., Helgason S., Gudmundsson S., et al. Herpes zoster in children and adolescents. Pediatr Infect Dis J 1998; 17: 905–8PubMedCrossRefGoogle Scholar
  7. 7.
    Latif R., Shope T.C. Herpes zoster in normal and immunocompromised children. Am J Dis Child 1983; 137: 801–2PubMedGoogle Scholar
  8. 8.
    Terada K., Kawano S., Yoshihiro K., et al. Characteristics of herpes zoster in otherwise normal children. Pediatr Infect Dis J 1993; 12: 960–1PubMedCrossRefGoogle Scholar
  9. 9.
    Kakourou T., Theodoridou M., Mostrou G., et al. Herpes zoster in children. J Am Acad Dermatol 1998; 39: 207–10PubMedCrossRefGoogle Scholar
  10. 10.
    Harding S.P., Porter S.M. Oral aciclovir in herpes zoster ophthalmicus. Curr Eye Res 1991; 10: 177–82PubMedCrossRefGoogle Scholar
  11. 11.
    Cobo M.L., Foulks G.N., Liesegang T.J., et al. Oral aciclovir in the therapy of acute herpes zoster ophthalmicus. Ophthalmology 1985; 92: 1574–83PubMedGoogle Scholar
  12. 12.
    Cobo M. Reduction of the ocular complications of herpes zoster ophthalmicus by oral acyclovir. Am J Med 1988; 85 Suppl. 2a: 90–3PubMedGoogle Scholar
  13. 13.
    Borruat F.X., Buechi E.R., Piquet B., et al. Prevention des complications oculaires de l’herpes zoster ophthalmique par un traitement adequat d’acyclovir. Klin Monatsbl Augenheilkd 1991; 198: 358–60PubMedCrossRefGoogle Scholar
  14. 14.
    Herbort C.P., Buechi E.R., Piquet B., et al. High-dose oral acyclovir in acute herpes zoster ophthalmicus: the end of the corticosteroid era. Curr Eye Res 1991; 10: 171–5PubMedCrossRefGoogle Scholar
  15. 15.
    Colin J., Prisant O., Cochener B., et al. Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology 2000; 107: 1507–11PubMedCrossRefGoogle Scholar
  16. 16.
    Balfour Jr H.H. Varicella-zoster virus infections in the immunocompromised host: natural history and treatment. Scand J Infect Dis 1991; 23 Suppl. 80: 69–74Google Scholar
  17. 17.
    Balfour H.H. Varicella zoster infections in immunocompromised hosts. Am J Med 1988; 85 Suppl. 2A: 68–73PubMedGoogle Scholar
  18. 18.
    Mandal B.K. Herpes zoster and the immunocompromised. J Infect 1987; 14: 15–9CrossRefGoogle Scholar
  19. 19.
    Nikkels A.F., Delvenne P., Sadzot-Delvaux C., et al. Distribution of varicella zoster virus and herpes simplex virus in disseminated fatal infections. J Clin Pathol 1996; 49: 243–8PubMedCrossRefGoogle Scholar
  20. 20.
    Han C.S., Miller W., Haake R., et al. Varicella zoster infection after bone marrow transplantation: incidence, risk factors and complications. Bone Marrow Transplant 1994; 13: 277–83PubMedGoogle Scholar
  21. 21.
    Nikkels A.F., Snoeck R., Rentier B., et al. Chronic verrucous varicella zoster virus skin lesions: clinical, histological, molecular and therapeutic aspects. Clin Exp Dermatol 1999; 24: 346–53PubMedCrossRefGoogle Scholar
  22. 22.
    Nikkels A.F., Piérard G.E. Recognition and treatment of shingles. Drugs 1994; 48: 528–48PubMedCrossRefGoogle Scholar
  23. 23.
    O’Brien J.J., Campoli-Richards D.M. Acyclovir: an updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989; 37: 233–309PubMedCrossRefGoogle Scholar
  24. 24.
    Wagstaff A.J., Faulds D., Goa K.J. Aciclovir: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47: 153–205PubMedCrossRefGoogle Scholar
  25. 25.
    Perry C.M., Faulds D. Valaciclovir: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpes virus infections. Drugs 1996; 52: 754–72PubMedCrossRefGoogle Scholar
  26. 26.
    Ormrod D., Goa K. Valaciclovir: a review of its use in the management of herpes zoster. Drugs 2000; 59: 1317–40PubMedCrossRefGoogle Scholar
  27. 27.
    Piérard G.E., Nikkels A.F. Le médicament du mois: le valaciclovir (Zelitrex). Rev Med Liege 1997; 52: 553–5PubMedGoogle Scholar
  28. 28.
    Nikkels A.F., Piérard G.E. Comment je traite: le zona. Rev Med Liege 1999; 54: 71–5PubMedGoogle Scholar
  29. 29.
    Nikkels A.F., Piérard G.E. Current therapies for shingles. Exp Opin Invest Drugs 1996; 5: 185–96CrossRefGoogle Scholar
  30. 30.
    Perry C.M., Wagstaff A.J. Famciclovir: a review of its pharmacological properties and therapeutic efficacy in herpes virus infections. Drugs 1995; 50: 396–415PubMedCrossRefGoogle Scholar
  31. 31.
    Dworkin R.H., Carrington D., Cunningham A., et al. Assessment of pain in herpes zoster: lessons learned from antiviral trials. Antiviral Res 1997; 33: 73–85PubMedCrossRefGoogle Scholar
  32. 32.
    Anonymous. A blue print for studies in herpes zoster. Expert Opin Herpes 1994; 7: 1–3Google Scholar
  33. 33.
    Wood M.J., Balfour H., Beutner K., et al. How should zoster trials be conducted? J Antimicrob Chemother 1995; 36: 1089–101PubMedCrossRefGoogle Scholar
  34. 34.
    Tyring S., Barbarash R.A., Nahlik J.E., et al. Collaborative famciclovir herpes zoster study group: famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Ann Intern Med 1995; 123: 89–96PubMedGoogle Scholar
  35. 35.
    Kalman C.M., Laksin O.L. Herpes zoster and zosteriform herpes simplex virus infections in immunocompetent patients. Am J Med 1986; 81: 775–8PubMedCrossRefGoogle Scholar
  36. 36.
    Bowsher D. The lifetime occurrence of herpes zoster and prevalence of postherpetic neuralgia: a retrospective study in an elderly population. Eur J Pain 1999; 3: 335–42PubMedCrossRefGoogle Scholar
  37. 37.
    Burgoon C.F., Burgoon J.S., Baldridge G.D. The natural history of herpes zoster. JAMA 1957; 164: 265–9CrossRefGoogle Scholar
  38. 38.
    Söltz-Szöts J. Kritische Bemerkungen sur Klinik und Therapie des Herpes Zoster. Zentralbl Haut u Geschlechtskrankheiten 1965; 38: 123–7Google Scholar
  39. 39.
    Helgason S., Petursson G., Gudmundsson S., et al. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with a long term follow up. BMJ 2000; 321: 794–6PubMedCrossRefGoogle Scholar
  40. 40.
    Helgason S., Sigurdsson J.A., Gudmundsson S. The clinical course of herpes zoster: a prospective study in primary care. Eur J Gen Pract 1996; 2: 12–6CrossRefGoogle Scholar
  41. 41.
    De Moragas J.M., Kierland R.R. The outcome of patients with herpes zoster. Arch Dermatol 1957; 75: 193–6CrossRefGoogle Scholar
  42. 42.
    Wood M.J., Ogan P.H., McKendrick M.W., et al. Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med 1988; 85: 79–83PubMedGoogle Scholar
  43. 43.
    Morton P., Thomson A.N. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J 1989; 102: 93–5PubMedGoogle Scholar
  44. 44.
    Beutner K.R., Friedman D.J., Forszpaniak C., et al. Valaciclovir compared with aciclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39: 1546–53PubMedCrossRefGoogle Scholar
  45. 45.
    Wood M.J., Johnson R.W., McKendrick M.W., et al. A randomized trial of aciclovir for 7 days or 21 days with and without prednisolone for the treatment of acute herpes zoster. N Engl J Med 1994; 330: 896–900PubMedCrossRefGoogle Scholar
  46. 46.
    Huff J.C., Bean B., Balfour H.H., et al. Therapy of herpes zoster with oral aciclovir. Am J Med 1988; 85: 84–9PubMedCrossRefGoogle Scholar
  47. 47.
    Wassilew S.W., Reimlinger S., Nasemann T., et al. Oral acyclovir for herpes zoster: a double-blind controlled trial in normal subjects. Br J Dermatol 1987; 117: 495–501PubMedCrossRefGoogle Scholar
  48. 48.
    Hoang-Xuan T., Buchi E.B., Herbort C.P., et al. Oral aciclovir for herpes zoster ophthalmicus. Ophthalmology 1992; 99: 1062–71PubMedGoogle Scholar
  49. 49.
    Whithley R.J., Weiss H., Gnann J.W., et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med 1996; 125: 376–83Google Scholar
  50. 50.
    Vander Straten M., Carrasco D., Lee P., et al. Reduction of postherpetic neuralgia in herpes zoster. J Cutan Med Surg 2001; 5: 409–16CrossRefGoogle Scholar
  51. 51.
    Crooks R.J., Jones D.A., Fiddian A.P. Zoster-associated chronic pain: an overview of clinical trials with aciclovir. Scand J Infect Dis 1991; 23 Suppl. 78: 62–8Google Scholar
  52. 52.
    Wood M.J., Kay R., Dworkin R.H., et al. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis 1996; 22: 341–7PubMedCrossRefGoogle Scholar
  53. 53.
    McKendrick M.W., Care C., Borke C., et al. Oral aciclovir in herpes zoster. J Antimicrob Chemother 1984; 14: 661–5PubMedCrossRefGoogle Scholar
  54. 54.
    McKendrick M.W., McGill J.I., Wood M.J. Lack of effect of acyclovir on postherpetic neuralgia. BMJ 1989; 298: 431PubMedCrossRefGoogle Scholar
  55. 55.
    Degreef H., and the Famciclovir Herpes Zoster Clinical Study Group. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in immunocompetent patients. Int J Antimicrob Agents 1994; 4: 241–6PubMedCrossRefGoogle Scholar
  56. 56.
    Anonymous. Famciclovir safe and effective for management of shingles. AIDS Patient Care STDS 1997; 11: 198Google Scholar
  57. 57.
    Tyring S., Belanger R., Bezwoda W., et al. A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients. Cancer Invest 2001; 19: 13–22PubMedCrossRefGoogle Scholar
  58. 58.
    Tyring S., Engst R., Corriveau C., et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol 2001; 85: 576–81PubMedCrossRefGoogle Scholar
  59. 59.
    Eaglestein W.H., Katz R., Brown J.A. The effects of early corticosteroid therapy on the skin eruption and pain of herpes zoster. JAMA 1970; 211: 1681–3CrossRefGoogle Scholar
  60. 60.
    Esmann V., Geil J.P., Kroon S., et al. Prednisolone does not prevent postherpetic neuralgia. Lancet 1987; II: 126–9CrossRefGoogle Scholar
  61. 61.
    Dworkin R.H., Boon R.J., Griffin D.R.G., et al. Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients. J Infect Dis 1998; 178 Suppl. 1: 71–5CrossRefGoogle Scholar
  62. 62.
    Whitley R.J., Gnann J.W. Herpes zoster: focus on treatment in older adults. Antiviral Res 1999; 44: 145–54PubMedCrossRefGoogle Scholar
  63. 63.
    Whitley R.J., Gnann Jr J.W., Weiss H.L., et al. Unique clinical trial design: combination acyclovir plus prednisone therapy of localized zoster in the normal host. Antiviral Res 1996; 29: 67–8PubMedCrossRefGoogle Scholar
  64. 64.
    Tyring S.K., Beutner K.R., Tucker B.A., et al. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valaciclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med 2000; 9: 863–9PubMedCrossRefGoogle Scholar
  65. 65.
    Choo P.W., Galil K., Donahue J.G., et al. Risk factors for postherpetic neuralgia. Arch Intern Med 1997; 157: 1217–24PubMedCrossRefGoogle Scholar
  66. 66.
    Alper B.S., Lewis P.R. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia? J Fam Pract 2000; 49: 255–64PubMedGoogle Scholar
  67. 67.
    Johnson R. Herpes zoster-predicting and minimizing the impact of post-herpetic neuralgia. J Antimicrob Chemother 2001; 47 Suppl. 1: 1–8PubMedCrossRefGoogle Scholar
  68. 68.
    Wacker P., Hartmann O., Benhamou E., et al. Varicella zoster virus infections after autologous bone marrow transplantation in children. Bone Marrow Transplant 1989; 4: 191–4PubMedGoogle Scholar
  69. 69.
    Perren R.J., Powles R.L., Easton D., et al. Prevention of herpes zoster in patients by long term oral acyclovir after allogenic bone marrow transplantation. Am J Med 1988; 85 Suppl. 2A: 99–101PubMedGoogle Scholar
  70. 70.
    Van Den Broek P.J., Van Der Meer J.W., Mulder J.D., et al. Limited value of acyclovir in the treatment of uncomplicated herpes zoster: a placebo controlled study. Infection 1984; 12: 338–41PubMedCrossRefGoogle Scholar
  71. 71.
    Marshall T. Postherpetic neuralgia: treatment with amitriptyline is cheaper than with aciclovir. BMJ 2001; 322: 860–1PubMedGoogle Scholar
  72. 72.
    Whitley R.J., Gnann Jr J.W., Hinthorn D., et al. Disseminated herpes zoster in the immunocompromised host: a comparative trial of acyclovir and vidarabine. J Infect Dis 1992; 165: 450–5PubMedCrossRefGoogle Scholar
  73. 73.
    Meyers J.D. Treatment of the varicella zoster infections in immunocompromised patients. Res Clin Forums 1986; 9: 65–74Google Scholar
  74. 74.
    Peterslund N.A. The treatment of herpes zoster infections. Scand J Infect Dis 1985; 17 Suppl. 47: 80–4Google Scholar
  75. 75.
    Petterson E., Hovi T., Ahonen J., et al. Prophylactic oral aciclovir after renal transplantation. Transplantation 1985; 39: 279–81CrossRefGoogle Scholar
  76. 76.
    Masaoka T., Hiraoka A., Teshima H., et al. Varicella zoster infection in immunocompromised patients. J Med Virol 1993; Suppl. 1: 82–4PubMedCrossRefGoogle Scholar
  77. 77.
    Levin M.J., Zaia J.A., Hershey B.J., et al. Topical acyclovir treatment of herpes zoster in immunocompromised patients. J Am Acad Dermatol 1985; 13: 590–6PubMedCrossRefGoogle Scholar
  78. 78.
    Rothe M.J., Feder Jr H.M., Grant-Kels J.M. Oral acyclovir therapy for varicella and zoster infections in pediatric and pregnant patients: a brief review. Pediatr Dermatol 1991; 8: 236–7PubMedCrossRefGoogle Scholar
  79. 79.
    Sempere A., Sanz G.F., Senent L., et al. Long-term acyclovir prophylaxis for prevention of varicella zoster virus infection after autologous blood stem cell transplantation in patients with acute leukemia. Bone Marrow Transplant 1992; 10: 495–8PubMedGoogle Scholar
  80. 80.
    Ljungman P., Lonnquist B., Ringden O., et al. A randomized trial of oral versus intravenous acyclovir for treatment of herpes zoster in bone marrow transplant recipients. Bone Marrow Transplant 1989; 4: 613–5PubMedGoogle Scholar
  81. 81.
    Ladriere M., Bibes B., Rabaud C., et al. Varicella zoster virus infection after bone marrow transplant: unusual presentation and importance of prevention. Presse Med 2001; 30: 1151–4PubMedGoogle Scholar
  82. 82.
    Yagi T., Karasuno T., Hasegawa T., et al. Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir. Bone Marrow Transplant 2000; 25: 1003–5PubMedCrossRefGoogle Scholar
  83. 83.
    Stemmer S.M., Kinsman K., Tellschow S., et al. Fatal noncutaneous visceral infection with varicella-zoster virus in a patient with autologous bone marrow tranplantation. Clin Inf Dis 1993; 16: 497–9CrossRefGoogle Scholar
  84. 84.
    Novelli V.M., Marshall W.C., Yeo J., et al. Acyclovir administered perorally in immunocompromised children with varicella zoster infections. J Infect Dis 1984; 149: 478PubMedCrossRefGoogle Scholar
  85. 85.
    Höglund M., Ljungman P., Weller S. Comparable aciclovir exposures produced by oral aciclovir in immunocompromised cancer patients. J Antimicrob Chemother 2001; 47: 855–61PubMedCrossRefGoogle Scholar
  86. 86.
    Bomgaars L., Duran C., Khan S., et al. The pharmacokinetics of valaciclovir in immunocompromised children [abstract]. Clin Pharmcol Ther 2000; 69: PI58Google Scholar
  87. 87.
    Levin M.J. Use of varicella vaccines to prevent herpes zoster in older individuals. Arch Virol 2001; 146 Suppl. 17: 151–60Google Scholar
  88. 88.
    Straus S.E. Varicella-zoster virus immunity and prevention: a conference perspective. Arch Virol 2001; 146 Suppl. 17: 173–8Google Scholar
  89. 89.
    Takahashi M., Kamiya H., Asano Y., et al. Immunization of the elderly to boost immunity against varicella-zoster virus (VZV) as assessed by VZV skin test reaction. Arch Virol 2001; 146 Suppl. 17: 161–72Google Scholar
  90. 90.
    Gershon A.A. The current status of live attenuated varicella vaccine. Arch Virol 2001; 146 Suppl. 17: 1–6Google Scholar

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© Adis International Limited 2002

Authors and Affiliations

  1. 1.University Medical Center, University of LiègeLiègeBelgium

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