Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults

Abstract

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three-to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged >50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P ‫؍‬ 0.001 and P ‫؍‬ 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients >50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.Herpes zoster remains an important medical problem throughout the world. The characteristic rash and associated pain occur when varicella-zoster virus, which becomes dormant in sensory ganglia following primary varicella-zoster virus infection, is reactivated, often in association with declining cellular immunity associated with advancing age (4). Thus, in otherwise healthy adults, the risk of herpes zoster increases with age (12). Pain persisting after rash healing occurs in more than 50% of untreated patients and is the major complication in older adults (3, 13). The pain is often accompanied by abnormal sensations such as allodynia, tingling, or numbness and decreases gradually over several months in most patients (2), although some patients have pain persisting beyond 6 months (8,13,20). Acyclovir (Zovirax) administered orally (800 mg five times daily) is widely used for treatment of acute herpes zoster. It speeds rash healing and decreases the severity of acute pain (14,18,25,28). In some studies, acyclovir also appears to reduce the prevalence, severity, and duration of chronic pain (7,11,14,18). Furthermore, oral acyclovir reduces the prevalence and severity of certain intraocular complications associated with herp...

Assessment of pain in herpes zoster: lessons learned from antiviral trials

“…Five papers which reported the results of antiviral trials of herpes zoster were reviewed by the participants (Degreef and the Famciclovir Herpes Zoster Clinical Study Group, 1994;Beutner et al, 1995;Tyring et al, 1995;Wood et al, 1994Wood et al, , 1996. The research designs, methods of data analysis, and results of these trials were systematically examined, in order to provide a basis for a comprehensive examination of the analysis of prolonged pain in herpes zoster trials.…”

“…Covariate analyses are valuable for examining factors that predict prolonged pain and better therapeutic response; for pivotal trials, however, such analyses should be few in number and prospectively identified, with adjustments made for multiple comparisons if necessary. Older age and greater pain severity at enrollment have been found to be associated with prolonged herpes zoster pain in a large number of studies (e.g., McKendrick et al, 1994;Boon and Griffin, 1995;Beutner et al, 1995;Dworkin et al, 1995bDworkin et al, , 1996Whitley et al, 1996;Wood et al, 1996). Because of these robust associations, these two factors should be examined in all studies of herpes zoster and PHN.…”

“…An alternative method has been employed to include all patients enrolled. Using this method, patients who do not have PHN are assigned a duration of PHN of zero days (Beutner et al, 1995;Wood et al, 1996). However, the number of such patients included in different treatment groups may not be balanced.…”

“…Therefore, a subgroup analysis of patients with moderate or greater pain severity at enrollment is recommended. Similarly, prodromal pain may influence the duration of prolonged pain (Beutner et al, 1995), and patients with prodromal pain for either less than 3 days, 3 days or more, or none at all, would be worthwhile subgroups to analyze. Furthermore, there is evidence that earlier therapy with some antivirals may result in faster resolution of pain (Degreef and the Famciclovir Herpes Zoster Clinical Study Group, 1994).…”

“…Wood and the Herpes Zoster Clinical Trial Consensus Group (1995) recently reported the results of a consensus meeting on herpes zoster pain that was held in July 1994. However, a number of seminal papers on the treatment of herpes zoster were not available at the time of this assessment (Degreef and the Famciclovir Herpes Zoster Clinical Study Group, 1994;Beutner et al, 1995;Tyring et al, 1995;Wood et al, 1996). A group of specialists therefore met to review the published data and assess the strengths and weaknesses of the various clinical trial designs and analyses.…”