Skip to main content
SpringerLink
Log in

Valaciclovir

A Review of its Long Term Utility in the Management of Genital Herpes Simplex Virus and Cytomegalovirus Infections

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Valaciclovir is an aciclovir prodrug used to treat infections caused by herpes simplex virus (HSV) and varicella zoster virus, and for prophylaxis against cytomegalovirus (CMV). Oral valaciclovir provides significantly better oral bioavailability than oral aciclovir itself, contributing to the need for less frequent administration.

Several studies have demonstrated the efficacy of long term (> 90 days) therapy with valaciclovir for the suppression of genital HSV disease in otherwise healthy individuals with HSV infection. In 1 randomised, double-blind trial, once daily valaciclovir (1000mg, 500mg and 250mg) produced statistically significant suppression of disease recurrence, as did twice daily valaciclovir 250mg and aciclovir 400mg. Valaciclovir dosages of ≥500mg daily are recommended for suppression of genital herpes recurrences in immunocompetent individuals. This disease occurs frequently in patients with human immunodeficiency virus (HIV) infection and, in a single randomised double-blind trial, prophylactic valaciclovir (1000mg once daily or 500mg twice daily) and aciclovir (400mg twice daily) were found to be of similar efficacy in the suppression of genital herpes. However, a higher than expected dropout rate indicated that more studies of valaciclovir in patients with HIV are required.

In a randomised trial of patients undergoing renal transplant, valaciclovir 2g 4 times daily for 90 days significantly reduced the incidence and delayed the onset of CMV disease: the incidence in valaciclovir-treated patients who were CMV-seronegative at baseline, and recieived a kidney from a CMV-seropositive donor, was 3% versus 45% for placebo after 90 days of treatment. Acute graft rejection was also reduced in the valaciclovir-treated group. A small study in heart transplant patients compared valaciclovir (2g 4 times daily) with aciclovir (200mg 4 times daily) and found a significant reduction in CMV antigenaemia favouring valacilovir at the end of the treatment period. Additional reductions in other indices of CMV in those given valaciclovir compared with aciclovir were also noted. In a preliminary study of prophylaxis for CMV disease in bone marrow transplant recipients valaciclovir (2g 4 times daily) was superior to aciclovir (800mg 4 times daily) in terms of time to CMV viraemia or viruria. Although valaciclovir (8 g/day for ≈30 weeks) reduced the incidence and time to CMV disease compared with aciclovir (3.2 g/day) in patients with advanced HIV disease, valaciclovir was associated with more gastrointestinal complaints and an increased risk of death, leading to premature termination of the study.

As yet, no trials comparing the efficacy of valaciclovir with famciclovir (the oral prodrug for penciclovir) in the suppression of recurrent episodes of genital herpes have been published, nor have direct comparisons been made between valaciclovir with ganciclovir in patients with CMV disease.

Valaciclovir is well tolerated at dosages used to suppress recurrent episodes of genital herpes (500 to 1000 mg/day) in immunocompetent and HIV seropositive individuals, with headache being reported most often. However, a potentially fatal thrombotic microangiopathy (TMA)-like syndrome has been reported in some immunocompromised patients receiving high-dose prophylactic valaciclovir therapy (8 g/day) for CMV disease for prolonged periods, and the risk of this syndrome appears to be higher in patients with advanced HIV disease. While the clinical benefits of valaciclovir in some immunocompromised patients may outweigh the risk of TMA, close monitoring for symptoms of TMA is indicated in all immunocompromised patients receiving high-dose valaciclovir.

Conclusion: Oral valaciclovir is an effective drug for the suppression of recurrent episodes of genital herpes in immunocompetent and immunocompromised individuals. It is as effective as oral aciclovir and has a similar tolerability profile, but in the recommended dosage requires less frequent administration in immunocompetent patients which may improve compliance in this group. Whether the possible compliance advantage will result in valaciclovir replacing aciclovir for this indication probably depends on pharmacoeconomic factors. In patients who have undergone renal transplantation, valaciclovir has demonstrated efficacy as prophylactic therapy for CMV infection and disease. There is also preliminary evidence supporting the use of valaciclovir to prevent CMV disease in heart and bone marrow transplant recipients. Valaciclovir is likely to become a valuable component of therapy in the management of renal transplant recipients. Further studies are required to establish the value of valaciclovir in the prevention of CMV disease in other transplant settings and in patients with HIV disease, and its efficacy relative to therapies other than aciclovir in these indications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Table II
Fig. 3
Table III
Fig. 4
Table IV
Table V
Fig. 5

References

  1. Balfour Jr HH. Antiviral drags. N Engl J Med 1999; 340(16): 1255–68

    Article  PubMed  CAS  Google Scholar 

  2. Perry CM, Faulds D. Valaciclovir: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesviras infections. Drags 1996 Nov; 52: 754–72

    Article  CAS  Google Scholar 

  3. Patel R. Valaciclovir: development, clinical utility and potential. Expert Opin Invest Drag 1997 Feb; 6: 173–89

    Article  CAS  Google Scholar 

  4. Wagstaff AJ, Faulds D, Goa KL. Aciclovir: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994 Jan; 47: 153–205

    Article  PubMed  CAS  Google Scholar 

  5. Saiag P, Praindhui D, Chastang C, et al. A double-blind, randomized study assessing the equivalence of valacyclovir 1000 mg once daily versus 500 mg twice daily in the episodic treatment of recurrent genital herpes. J Antimicrob Chemother 1999; 44: 525–31

    Article  PubMed  CAS  Google Scholar 

  6. World Health Organization. Prevention and control of herpes-virus diseases. Part 1. Clinical and laboratory diagnosis and chemotherapy. A WHO meeting. Bull World Health Organ 1985; 63(2): Geneva, 185–201

    Google Scholar 

  7. Fleming DT, McQuillian GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997; 337(16): 1105–11

    Article  PubMed  CAS  Google Scholar 

  8. Andersson-Ellström A, Svennerholm B, Forssman L. Prevalence of antibodies to herpes simplex virus types 1 and 2, Epstein-Barr virus and cytomegalovirus in teenage girls. Scand J Infect Dis 1995; 27: 315–8

    Article  PubMed  Google Scholar 

  9. Puthavathana P, Kanyok R, Horthongkham N, et al. Prevalence of herpes simplex virus infection in patients suspected of genital herpes; and virus typing by type specific fluorescent monoclonal antibodies. J Med Assoc Thai 1998; 81(4): 260–4

    PubMed  CAS  Google Scholar 

  10. Hashido M, Lee FK, Nahmias AJ, et al. An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays. Epidemiol Inf 1998; 120(2): 179–86

    Article  CAS  Google Scholar 

  11. Goldmeier D, Johnson A, Byrne M, et al. Psychosocial implications of recurrent genital herpes simplex virus infections. Genitourin Med 1988; 64: 327–30

    PubMed  CAS  Google Scholar 

  12. Manne S, Sandler I. Coping and adjustment to genital herpes. J Behav Med 1984; 7: 391–410

    Article  PubMed  CAS  Google Scholar 

  13. Bodsworth NJ, Crooks RJ, Borelli S, et al. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. Genitourin Med 1997 Apr; 73: 110–6

    PubMed  CAS  Google Scholar 

  14. Spruance SL, Tyring SK, DeGregorio B, et al. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group. Arch Intern Med 1996 Aug 12–26; 156: 1729–35

    CAS  Google Scholar 

  15. Tyring SK, Douglas Jr JM, Corey L, et al. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. Arch Dermatol 1998 Feb; 134: 185–91

    Article  PubMed  CAS  Google Scholar 

  16. Stocchi R, Ward KN, Fanin R, et al. Management of human cytomegalovirus infection and disease after allogeneic bone marrow transplantation. Haematologica 1999 Jan; 84: 71–9

    PubMed  CAS  Google Scholar 

  17. Enright H, Haake R, Weisdorf D, et al. Cytomegalovirus pneumonia after bone marrow transplantation. Transplantation 1993; 55(6): 1339–46

    Article  PubMed  CAS  Google Scholar 

  18. Ljungman P. Cytomegalovirus infections in transplant patients. Scand J Infect Dis Suppl 1996; 100: 59–63

    PubMed  CAS  Google Scholar 

  19. Reusser P. Human cytomegalovirus infection and disease after bone marrow and solid organ transplantation. Baillieres Clin Infect Dis 1996; 3: 357–71

    Google Scholar 

  20. Gallant JE, Moore RD, Richman DD, et al. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. J Infect Dis 1992; 166: 1223–7

    Article  PubMed  CAS  Google Scholar 

  21. Hoover DR, Saah AJ, Bacellar H. Clinical manifestations of AIDS in the era of pneumocystis prophylaxis. N Engl J Med 1993; 329(26): 1922–6

    Article  PubMed  CAS  Google Scholar 

  22. Baldassano V, Dunn JP, Feinberg J, et al. Cytomegalovirus retinitis and low CD4+ T-lymphocyte counts. N Engl J Med 1995; 333(10): 670

    Article  PubMed  CAS  Google Scholar 

  23. Kuppermann BD, Petty JG, Richman DD, et al. Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993; 115: 575–82

    PubMed  CAS  Google Scholar 

  24. Deayton J, Mocroft A, Wilson P, et al. Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy. AIDS 1999; 13(10): 1203–6

    Article  PubMed  CAS  Google Scholar 

  25. Beauchamp LM, Krenitsky TA. Acyclovir prodrugs: the road to valaciclovir. Drugs Future 1993 Jul; 18: 619–28

    Google Scholar 

  26. Crooks RJ. Valaciclovir — a review of its potential in the management of genital herpes. Antiviral Chem Chemother 1995; 6 Suppl. 1: 39–44

    CAS  Google Scholar 

  27. Beutner KR. Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antiviral Res 1995 Dec; 28: 281–90

    Article  PubMed  CAS  Google Scholar 

  28. Glaxo Wellcome. Valtrex® (valacyclovir hydrochloride) caplets. Product information. 1999, Research Triangle Park (NC)

  29. Takahashi K, Suzuki M, Iwata Y, et al. Selective activity of various nucleoside and nucleotide analogues against human herpesvirus 6 and 7. Antiviral Chem Chemother 1997; 8(1): 24–31

    CAS  Google Scholar 

  30. Kedes DH, Ganem D. Sensitivity of Kaposi’s sarcoma-associated herpesvirus replication to antiviral drugs: implications for potential therapy. J Clin Invest 1997; 99(9): 2082–6

    Article  PubMed  CAS  Google Scholar 

  31. Medveczky MM, Horvath E, Lund T, et al. In vitro antiviral drug sensitivity of the Kaposi’s sarcoma-associated herpesvirus. AIDS 1997; 11: 1327–32

    Article  PubMed  CAS  Google Scholar 

  32. Collins P, Ellis MN. Sensitivity monitoring of clinical isolates of herpes simplex virus to acyclovir. J Med Virol 1993; Suppl. 1:58-66

    Google Scholar 

  33. Darby G, Field HJ. Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. Nature 1981; 289: 81–3

    Article  PubMed  CAS  Google Scholar 

  34. Larder BA, Darby G. Virus drug-resistance: mechanisms and consequences. Antiviral Res 1984; 4(4): 1–42

    Article  PubMed  CAS  Google Scholar 

  35. Snowden W, Manohitharajah V, Crooks J. Antiviral sensitivity of herpes simplex virus isolates from patients participating in the valaciclovir gnital herpes simplex programme [abstract no. M175]. Antiinfect Drugs Chemother 1998; 16 Suppl. 1

  36. Neyts J, de Clercq E. Antiviral drug susceptibility of human herpesvirus 8. Antimicrob Agents Chemother 1997; 41(12): 2754–6

    PubMed  CAS  Google Scholar 

  37. Champness JN, Bennett MS, Wein F, et al. Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands. Proteins 1998; 32(3): 350–61

    Article  PubMed  CAS  Google Scholar 

  38. Wetherall NT, Hodges-Savola CA, Reyes M, et al. Acyclovir-resistant herpes simplex virus: characterization of virus isolates from a nationwide surveillance system [abstract no. 17]. Antiviral Res 1998; 37(3): A44

    Google Scholar 

  39. Gnann JW, Clark FM, Hodges-Savola CA, et al. Acyclovir-resistant herpes simplex virus in HIV-infected individuals: results from an ongoing US surveillance study [abstract no. 86]. Antiviral Res 1999; 41(2): A59

    Google Scholar 

  40. Reyes M, Graber JM, Weatherall N, et al. Acyclovir-resistant herpes simplex virus: preliminary results from a national surveillance system [abstract no. 17]. Antiviral Res 1998; 37(3): A44

    Google Scholar 

  41. Weinberg A, Schneider SA, Clark JC, et al. Acyclovir (ACV) and valacyclovir (VAL) prophylaxis of AIDS patients does not alter cytomegalovirus (CMV) susceptibility to ganciclovir (GCV) or foscarnet (FOS) [abstract]. 36th Interscience Conference on Antimicrobial Agents and Chemotherapy 1996 Sep, New Orleans, La 15: 202

    Google Scholar 

  42. Weller S, Blum MR, Doucette M, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther 1993 Dec; 54: 595–605

    Article  PubMed  CAS  Google Scholar 

  43. Soul-Lawton J, Weller S, On N, et al. Oral valaciclovir — increased acyclovir bioavailability in different patient populations [abstract no. P59]. AIDS 1994 Nov; 8 Suppl. 4: S33

    Article  Google Scholar 

  44. de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother 1983; 12 Suppl. B: 29–37

    Article  PubMed  Google Scholar 

  45. Soul-Lawton J, Seaber E, On N, et al. Absolute bioavailability and metabolic disposition of valaciclovir, the 1-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother 1995; 39(12): 2759–64

    Article  PubMed  CAS  Google Scholar 

  46. First MR, Blum MR, Brennan P, et al. Pharmacokinetics (PK) of 256U87, an acyclovir (ACV) prodrug in renal transplant (RTX) patients [abstract]. Clin Pharmacol Ther 1993 Feb; 53: 238

    Google Scholar 

  47. Wang LH, Schultz M, Weller S, et al. Pharmacokinetics and safety of multiple-dose valaciclovir in geriatric volunteers with and without concomitant diuretic therapy. Antimicrob Agents Chemother 1996 Jan; 40: 80–5

    PubMed  CAS  Google Scholar 

  48. Jacobson MA, Gallant J, Wang LH, et al. Phase I trial of valaciclovir, the 1-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother 1994 Jul; 38: 1534–40

    Article  PubMed  CAS  Google Scholar 

  49. Conant MA, Murphy R, Thompson S, et al. Valaciclovir for the management of recurrent herpes simplex virus infection in HIV-infected individuals — two double-blind controlled trials. Boehringer Ingelheim, US, 1999 (Data on file)

  50. On NT, Ehninger G, Gluckman E, et al. Acyclovir pharmacokinetics following oral multiple-dose of valaciclovir (Valtrex®) in allogeneic BMT patients [abstract]. Bone Marrow Transplant 1995 Mar; 15 Suppl. 2: S122

    Google Scholar 

  51. Guo A, Hu P, Balimane PV, et al. Interactions of a nonpeptide drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line. J Pharmacol Exp Ther 1999; 289: 448–54

    PubMed  CAS  Google Scholar 

  52. Bras AP, Sitar DS, Aoki F. Comparative bioavailability of acyclovir from oral valacyclovir and acyclovir in patients treated for recurrent genital herpes simplex virus infection. Can J Clin Pharmacol (in press)

  53. Steingrimsdottir H, Gruber A, Palm C, et al. Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy. Antimicrob Agents Chemother 2000; 44(1): 207–9

    Article  PubMed  CAS  Google Scholar 

  54. Eksborg S, Kallin N, Pal C, et al. Pharmacokinetics of aciclovir after intravenous and oral administration as its pro-drug valaciclovir in immunocompromised children with mucosites [abstract]. 8th International Congress of Infectious Diseases; 1998 May 17; Boston, Ma, poster 47.025

  55. Reitano M, Tyring S, Lang W, et al. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. J Infect Dis 1998 Sep; 178: 603–10

    Article  PubMed  CAS  Google Scholar 

  56. Patel R, Bell AR. Valaciclovir for the suppression of recurrent genital herpes:relationship between efficacy and pharmacokinetic parameters [abstract no. M176]. Antiinfect Drugs Chemother 1998; 16 Suppl. 1: 19

    Google Scholar 

  57. Kimberlin DF, Weller S, Whitley RJ, et al. Pharmacokinetics of oral valacyclovir in late pregnancy. Am J Obstet Gynecol 1998; 179(4): 846–51

    Article  PubMed  CAS  Google Scholar 

  58. Höglund M, Ljungman P, Larsson R, et al. Comparable aciclovir exposures produced by oral valaciclovir and intravenous aciclovir in immunocompromised cancer patients [abstract no.P7]. J Antimicrob Chemother 1999; 44 Suppl. A: 42

    Google Scholar 

  59. Simon MW, Fish D, Deeter RG. Pharmacokinetics and safety of valaciclovir in children with EBV illness [abstract no. 48.006]. 8th International Congress on Infections Disease; 1998 May 17; Boston (MA), 131

  60. De Bony F, Bidault R, Tod M, et al. Interaction of cimetidine and probenecid with valaciclovir and its metabolite acyclovir [abstract]. 36th Interscience Conference on Antimicrobial Agents and Chemotherapy 1996 Sep 15: 6

    Google Scholar 

  61. Patel R, Bodsworth NJ, Woolley P, et al. Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. Genitourin Med 1997 Apr; 73: 105–9

    PubMed  CAS  Google Scholar 

  62. Baker DA, Blythe JG, Miller JM. Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes. Obstet Gynecol 1999 Jul; 94: 103–6

    Article  PubMed  CAS  Google Scholar 

  63. Lawrence AG, Bell AR. Valaciclovir for prevention of recurrent herpes simplex virus infection in HIV-infected individuals — a double-blind controlled trial [abstract no. P1426]. Clin Microbiol Infect 1997; 3 Suppl. 2: 353

    Google Scholar 

  64. Mertz GJ, Jones CC, Mills J, et al. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection: a multicenter double-blind trial. JAMA 1988; 260(2): 201–6

    Article  PubMed  CAS  Google Scholar 

  65. Baker DA, Safrin S, Deeter RG, et al. Nine year effectiveness of continuous suppressive therapy with acyclovir (ACV) in patients with recurrent genital herpes (RGH) [abstract no. P220]. J Eur Acad Dermatol Venereol 1995; 5 Suppl. 1: S169

    Article  Google Scholar 

  66. Pouteil-Noble C, Ecochard R, Landrivon G, et al. Cytomegalo-virus infection — an etiological factor for rejection? Transplantation 1993; 55(4): 851–7

    Article  PubMed  CAS  Google Scholar 

  67. Ho M. Cytomegalovirus infection and indirect sequelae in the immunocompromised transplant patient. Transplant Proc 1991; 23(2) Suppl. 1: 2–7

    PubMed  CAS  Google Scholar 

  68. Rubin RH. Impact of cytomegalovirus on organ transplant recipients. Rev Infect Dis 1990; 12 Suppl. 7: S754–66

    Article  PubMed  Google Scholar 

  69. Lowance D, Neumayer H-H, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med 1999; 340: 1462–70

    Article  PubMed  CAS  Google Scholar 

  70. Egan J, Sheikh S, Woodcock A, et al. Valaciclovir reduces the incidence of cytomegalovirus infection in heart transplant patients. 9th Congress of the European Society for Organ Transplantation; 1999 June 19–24; Oslo, abstract no. 151

  71. Schmader K. Management of herpes zoster in elderly patients. Infect Dis Clin Pract 1995 Jul–Aug; 4: 293–9

    Article  Google Scholar 

  72. Keating MR, Fauchald P, Grant DM, et al. Impact of valaciclovir for cytomegalovirus prophylaxis on medical resource use in renal allograft recipients [abstract]. 8th International Congress on Infections Diseases 1998 May 15: 80

    Google Scholar 

  73. Norman D, Keating M, Fauchald P, et al. Economic analysis of valaciclovir prophylaxis of cytomegalovirus infection and disease in renal transplantation [abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy 1998 Sep 24: 609. San Diego, Cal

    Google Scholar 

  74. Meyers JD, Flournoy N, Thomas ED. Risk factors for cytomegalovirus infection after human marrow transplantion. J Infect Dis 1986; 153: 478–88

    Article  PubMed  CAS  Google Scholar 

  75. Prentice HG, Gluckman E, Powles RL, et al. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. Lancet 1994 Mar 26; 343: 749–53

    Article  PubMed  CAS  Google Scholar 

  76. Ljungman P. Efficacy and safety of valaciclovir as a prophylaxis against CMV infection and disease in BMT recipients [abstract/poster]. J Clin Virol 1999 Apr; 12(2): G6–02

    Article  Google Scholar 

  77. Feinberg JE, Hurwitz S, Cooper D, et al. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. J Infect Dis 1998 Jan; 177: 48–56

    Article  PubMed  CAS  Google Scholar 

  78. Griffiths PD, Feinberg JE, Fry J, et al. The effect of valaciclovir on cytomegalovirus viremia and viruria detected by polymerase chain reaction in patients with advanced human immunodeficiency virus disease. J Infect Dis 1998 Jan; 177: 57–64

    Article  PubMed  CAS  Google Scholar 

  79. Emery VC, Sabin C, Feinberg JE, et al. Quantitive effects of valacyclovir on the replication of cytomegalovirus (CMV) in persons with advanced human immunodeficiency virus disease: baseline CMV load dictates time to disease survival. J Infect Dis 1999; 180: 695–701

    Article  PubMed  CAS  Google Scholar 

  80. Tilson HH, Engle CR, Andrews EB. Safety of acyclovir: a summary of the first 10 years experience. J Med Virol 1993; 41 Suppl. 1: 67–73

    Article  Google Scholar 

  81. Fife KH, Barbarash RA, Rudolph T, et al. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection: results of an international, multicenter, double-blind, randomized clinical trial. Sex Transm Dis 1997 Sep; 24: 481–6

    Article  PubMed  CAS  Google Scholar 

  82. Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995 Jul; 39: 1546–53

    Article  PubMed  CAS  Google Scholar 

  83. Patel R, Bell AR. Valaciclovir for prevention of genital herpes simplex virus recurrences — long term safety [abstract]. J Clin Microbiol Infect 1997; 3 Suppl. 2: 352–3

    Article  Google Scholar 

  84. Bell WR, Chulay JD, Feinberg JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalo-virus prophylaxis trial (ACTG 204). Medicine 1997; 76: 369–80

    Article  PubMed  CAS  Google Scholar 

  85. Maslo C, Peraldi M-N, Desenclos J-C, et al. Thrombotic microangiopathy and cytomegalovirus disease in patients infected with human immunodeficiency virus. Clin Infect Dis 1997; 24: 350–5

    Article  PubMed  CAS  Google Scholar 

  86. The Wellcome Foundation. Valtrex™. Summary of product characteristics. 1999, Greenford, UK

  87. Glaxo Wellcome Oy. Valtrex™. Summary of product characteristics. 1999, Espoo, Finland

  88. Glaxo Wellcome. Zelitrex™. Summary of product characteristics. 2000, Marly-Le-Roi, France

  89. Mindel A. Genital herpes: role of acyclovir. J Paediatr Obst Gynaecol 1996 Nov–Dec; 22: 27–30

    Google Scholar 

  90. Alrabiah FA, Sacks SL. New antiherpesvirus agents: their targets and therapeutic potential. Drugs 1996 Jul; 52: 17–32

    Article  PubMed  CAS  Google Scholar 

  91. Field HJ, Tewari D, Sutton D, et al. Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model. Antimicrob Agents Chemother 1995 May; 39: 1114–9

    Article  PubMed  CAS  Google Scholar 

  92. Thackray AM, Field HJ. Comparison of effects of famciclovir and valaciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model. Antimicrob Agents Chemother 1996 Apr; 40: 846–51

    PubMed  CAS  Google Scholar 

  93. Thackray AM, Field HJ. Famciclovir and valaciclovir differ in the prevention of herpes simplex virus type 1 latency in mice: a quantitative study. Antimicrob Agents Chemother 1998; 42(7): 1555–62

    PubMed  CAS  Google Scholar 

  94. LeBlanc RA, Pesnicak L, Godleski M, et al. The comparative effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice. J Infect Dis 1999; 180: 594–9

    Article  Google Scholar 

  95. Wald A, Corey L. Antiviral therapies for long-term suppression of genital herpes [letter]. JAMA 1999; 281(13): 1169–70

    Article  PubMed  CAS  Google Scholar 

  96. Noble S, Faulds D. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs 1998 Jul; 56: 115–46

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 10, New Zealand

    Douglas Ormrod, Lesley J. Scott & Caroline M. Perry

Authors
  1. Douglas Ormrod
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Douglas Ormrod.

Additional information

Various sections of the manuscript reviewed by: D.A. Baker, Department of Obstetrics Gynecology and Reproductive Medicine, Stony Brook University Hospital and Medical Center, Stony Brook, New York, USA; Dr K.R. Beutner, Solano Dermatology Associates, Vallejo, California, USA; A. Breckenridge, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, England; C.P. Conlon, Nuffield Department of Medicine, John Radcliff Hospital, Oxford, England; H.J. Field, Centre for Veterinary Science, University of Cambridge, Cambridge, England; P. Ljungman, Department of Internal Medicine, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden; D. Lowance, Department of Internal Medicine, Piedmont Hospital, Atlanta, Georgia, USA; E.H. Wiltink, Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands; P. Woolley, Department of Genitourinary Medicine, University Hospital of South Manchester, Withington, Manchester, England.

Data Selection

Sources: Medical literature published in any language since 1997 on valaciclovir, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand) and Medline. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘Valaciclovir’ or ‘Valtrex’ or ‘BW256U’ or ‘256U87’. Medline search terms were ‘Valaciclovir’ or ‘Valtrex’ or ‘BW256U’ or ‘256U87’. Searches were last updated 13 March 2000.

Selection: Studies in patientswith herpes simplex virus infection or cytomegalovirus infectionwho received valaciclovir for ≥90 days. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Valaciclovir, prophylaxis, herpes simplex virus, cytomegalovirus, pharmacodynamics, pharmacokinetics, therapeutic use.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ormrod, D., Scott, L.J. & Perry, C.M. Valaciclovir. Drugs 59, 839–863 (2000). https://doi.org/10.2165/00003495-200059040-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200059040-00013

Search

Navigation