Once-daily oral valacyclovir is as good as twice-daily oral acyclovir for preventing the recurrence of eye disease caused by herpes simplex virus, according to a recent study.
In a randomized, controlled trial, Dr. Elisabetta Miserocchi of the San Raffaele Scientific Institute, Milan, and her colleagues compared 26 patients taking a single 500-mg tablet of valacyclovir daily with 26 patients taking 400-mg tablets of acyclovir twice daily (Am. J. Ophthalmol. 2007 Aug. 9 [Epub doi:10.1016/j.ajo.2007.06.001]).
All patients were immunocompetent and had a history of recurrent ocular herpes simplex virus (HSV) disease. By the end of 12 months of daily therapy, six of the patients in the valacyclovir group and six of the patients in the acyclovir group (23% in both cases) experienced a recurrence of ocular HSV.
Both drugs were well tolerated, and the incidence of adverse events was similar in both groups. Gastrointestinal upset and headache were the most frequent treatment-related side effects. Three patients in the valacyclovir group and four patients in the acyclovir group experienced nausea and vomiting, and five patients in the valacyclovir group and three patients in the acyclovir group experienced headache.
The investigators noted that HSV is the leading cause of corneal opacity and secondary visual loss in the United States and other industrialized countries, affecting some 450,000 people, with 50,000 new and recurrent cases each year. Recurrent episodes are frequent, with about 10% of patients reporting recurrence at 1 year, 23% at 2 years, and 63% at 20 years.
Although acyclovir is effective at preventing HSV recurrence, the drug has relatively poor oral bioavailability, and resistant isolates may develop. Valacyclovir is a prodrug of acyclovir, and is rapidly converted to acyclovir after administration. Plasma concentrations after oral valacyclovir are similar to plasma concentrations after intravenous acyclovir.
The authors acknowledged that valacyclovir treatment is more costly than acyclovir treatment, and that even acyclovir prophylaxis costs about $8,532 per ocular HSV episode averted, according to one study. Because this is not cost effective for all patients, "therapeutic decisions must be made on a case-by-case basis; prophylactic therapy may be appropriate for patients with sight-threatening recurrences, frequent episodes, or other reasons for reduced quality of life caused by ocular herpes," wrote Dr. Miserocchi and her associates.
They posited that the single daily dose of valacyclovir is likely to result in better compliance than is the multiple daily doses required with acyclovir. Therefore, valacyclovir may be particularly beneficial in cases of acyclovir-resistant HSV in which high-dose systemic or intravenous treatment with acyclovir has been necessary, and in which the resistance has been attributed to inadequate drug exposure.
"Because the optimal levels of acyclovir are achieved with a simpler dosing regimen of valacyclovir, compliance may be improved in many patients, thus reducing the incidence of a resistant virus," the investigators wrote. "A compound with improved absorption and bioavailability theoretically would extend the therapeutic usefulness of the drug."
The investigators stated that they had no conflicts of interest related to their study.