Valacyclovir for the Management of Herpes Viral Infections

A. Chakrabarty, MD; N. J. Anderson, MD; R. Beutner, MD, PhD; S. K. Tyring, MD, PhD, MBA

Disclosures

Skin Therapy Letter. 2005;10(1):1-4. 

In This Article

Clinical Indications

The antiviral spectrum of valacyclovir encompasses HSV1, HSV-2, VZV. The predominant clinical indications are orofacial herpes, genital herpes, herpes zoster and to a lesser degree, cytomegalovirus prophylaxis for transplant patients ( Table 2 ). An alternative antiviral for these clinical indications is another second-generation antiviral, famciclovir (Famvir®, Novartis), the prodrug of penciclovir. These antivirals have limitations as they provide no cure for infections, but instead alter the clinical course of the disease.

Valacyclovir is utilized for the management of orofacial herpes. HSV-1 is primarily associated with this condition. A short course of high dose valacyclovir at 2,000mg twice daily for 1 day is the recommended dose for initial treatment of orofacial herpes, usually commenced during the prodromal phase.[2] Another study demonstrated that valacyclovir 500mg, po, b.i.d. for 10-14 days is an effective prophylactic strategy against orofacial herpes recurrence starting 1 day prior to laser cutaneous resurfacing.[3] Smaller placebo-controlled trials have demonstrated the benefit of valacyclovir 500mg once daily for 4 months as a well-tolerated and effective therapy for the suppression of recurrent herpes labialis.[4] The higher bioavailability of valacyclovir enables less frequent administration compared to acyclovir.

HSV-2 is accountable for the majority of genital herpes, although HSV-1 is playing an increasing role in the epidemic. Treatment of genital herpes is categorized into primary, episodic, and suppressive regimens. Valacyclovir is approved by the US FDA at 1,000mg, po, two times daily for 10 days for initial onset of genital herpes and at a 3-day, 500mg, twice-daily course for episodic management of recurrent herpes.[5] Suppressive therapy is preferred when recurrences are frequent, severe, and/or emotionally disturbing. An open-label study demonstrated the preference of suppressive therapy with valacyclovir as once-daily therapy over the episodic dose of twice-daily therapy with lower recurrence rates and higher satisfaction levels noted in the suppressive cohort.[6] The treatment stratification of suppressive therapy is based on the annual number of recurrences.[7] For patients with <10 annual recurrences, 500mg of daily valacyclovir is recommended. For patients with >10 recurrences, 1,000mg valacyclovir daily, 250mg valacyclovir twice daily, or 400mg acyclovir twice daily were noted to be beneficial according to a subgroup analysis for different dosages. The once daily dosing provides a more patient-friendly approach, enabling greater compliance with antiviral therapy.[7] For HIV positive patients, valacyclovir 500mg twice daily or 1,000mg once daily is considered effective.[8] The suppressive strategy of valacyclovir therapy is being explored for primary episodes of genital herpes. This study is being conducted by Dr. Beutner in Davis. The treatment strategy will evaluate whether suppressive dosing can reduce the frequency and duration of recurrences as initial management for primary genital herpes.

Genital herpes transmission reduction is a recent supplemental indication for valacyclovir. Corey, et al. demonstrated the significant reduction of HSV-2 transmission among heterosexual, discordant couples with once-daily, 500mg valacyclovir.[9] The study revealed a 50% decrease in HSV-2 acquisition among susceptible partners and a more dramatic 75% symptomatic reduction of HSV-2 among susceptible partners when the infected partner received once-daily valacyclovir for 8 months. When combined with safe sexual practices (i.e., condom use), valacyclovir has been shown to reduce the transmission of genital herpes. The same study noted a reduction in asymptomatic viral shedding as an additional benefit. Most cases of transmission occur during periods of asymptomatic viral shedding.

Valacyclovir is indicated for the management of herpes zoster. Beutner, et al. demonstrated the benefit of valacyclovir 1,000mg 3x daily for 7 days in reducing the duration and proportion of postherpetic neuralgia at 6 months for patients >50 years old in comparison to acyclovir.[10] As well, no additional benefit was noted beyond 7 days of valacyclovir therapy when compared to a 14 day regime. Tyring, et al. conducted a comparison trial of valacyclovir vs. famciclovir, which did not reveal any significant differences between either antiviral in the treatment of herpes zoster.[11] The main advantage of valacyclovir would be cost-effectiveness which takes into consideration the cost of patient hospital stay. Although acyclovir is cheaper, the intravenous route is offset by the costs of inpatient hospitalization. Combination strategies for the management of herpes zoster are also being considered. When incorporating an anticonvulsant, such as gabapentin, with an antiviral, such as valacyclovir, paients exhibited pain reduction in an open-label, pilot trial.[12] Immunocompromised patients, such as HIV and cancer patients, can suffer from more severe manifestations of herpes zoster than immunocompetent patients. There are no current published studies documenting the benefit of valacyclovir for herpes zoster among the immunocompromised. A higher dosing regimen of valacyclovir for acute herpes zoster may provide a convenient, efficacious, cost-effective, and practical alternative to intravenous acyclovir administration for immunocompromised patients. Dr. Tyring is evaluating a higher dose of valacyclovir at 2,000mg, po, 3x daily vs. 1,000mg, po, 3x daily for 7 days as management of acute herpes zoster in immunocompromised patients. The benefit of the higher dosing valacyclovir will be determined after completion of the randomized, double-blinded study. Valacyclovir provides an effective antiviral in the treatment of herpes zoster and further trials of various dosing regimens of the antiviral pertaining to different clinical manifestations of herpes zoster are ongoing.

Cytomegalovirus (CMV) is a major pathogen resulting in considerable morbidity and mortality subsequent to solid organ and bone marrow transplantation. Antiviral prophlyaxis offers an effective strategy compared to the wait and treat approach. Prophylactic therapy with valacyclovir 2,000mg, 4x daily for 90 days immediately after renal transplantation reduced the incidence of CMV disease, as well as delaying its onset.[13] A separate comparison trial of oral valacyclovir vs. oral ganciclovir demonstrated similar levels of safety and efficacy in the prophylaxis of CMV disease after renal transplantation.[14] Valacyclovir is also utilized as preventive therapy for CMV for cardiac and bone marrow transplant recipients.

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