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 (1000 mg, 500 mg and 250 mg) produced statistically significant suppression of disease recurrence, as did twice daily
valaciclovir 250 mg and
aciclovir 400 mg.
Valaciclovir dosages of > or = 500 mg 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 (1000 mg once daily or 500 mg twice daily) and
aciclovir (400 mg 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 2 g 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 (2 g 4 times daily) with
aciclovir (200 mg 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 (2 g 4 times daily) was superior to
aciclovir (800 mg 4 times daily) in terms of time to CMV viraemia or viruria. Although
valaciclovir (8 g/day for approximately 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: