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- Title
Valaciclovir: A Review of its Long Term Utility in the Management of Genital Herpes Simplex Virus and Cytomegalovirus Infections.
- Authors
Ormrod, D.; Scott, L.J.; Perry, C.M.
- 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, valaciclovir and aciclovir produced similar and statistically significant suppression of disease recurrence. Notably, valaciclovir 1000mg once daily suppressed recurrent episodes of genital herpes, in contrast to the twice daily regimen required when aciclovir 400mg was used. 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.
- Subjects
ANTIBACTERIAL agents; HERPES genitalis treatment; CYTOMEGALOVIRUS disease treatment
- Publication
Drugs, 2000, Vol 59, Issue 4, p839
- ISSN
0012-6667
- Publication type
Article