Valacyclovir (Valtrex) Part 2: New indication

September 2003

Herpes labialis, more commonly known as herpes simplex virus-1 (HSV-1), is predominantly associated with herpetic lesions located in the oropharyngeal area. In some cases, HSV-2 can be the cause of the lesions. These lesions are usually located on the lips and usually crust over within 72 to 96 hours. Viral replication and shedding occur during active infection. It is during this time that the virus can be spread to an uninfected person. With HSV-1 infections, viral shedding continues for about 48 hours during a primary or recurrent infection.

Treatment of HSV-1 with antivirals has not been considered highly effective.

Until recently, topical 1% penciclovir cream (Denavir, GlaxoSmithKline) was the only FDA-approved prescription therapy available for this condition. Topical penciclovir was approved after demonstrating a 0.7 day faster healing period and a decrease in viral shedding compared with placebo. In addition, docosanol cream (Abreva, GSK) is available as the first over-the-counter product indicated for the treatment of recurrent herpes labialis episodes. Docosanol was determined to decrease the time to lesion healing by approximately one-half day if therapy was started within 12 hours of symptoms of infection.

Oral acyclovir has been studied for the treatment of recurrent herpes labialis outbreaks, prophylaxis against sun-induced lesions, as well as for suppressive therapy with variable results. Studies have demonstrated that patients who suffered from distinguishable prodromal symptoms benefited more from oral acyclovir therapy than those patients who never suffered from a prodrome. In addition, oral acyclovir is not FDA-approved for any of these indications.

A supplemental new drug application is being investigated for the use of famciclovir in the treatment of initial herpes labialis infections. Higher doses of famiciclovir (Famvir, Novartis) have been shown to be more effective than lower doses in decreasing the time to lesion healing. Studies are still underway to determine the optimal dose and duration for famciclovir therapy. It is currently approved only for use in immunocompromised patients.

One-day therapy

In September 2002, the FDA approved valacyclovir (Valtrex, GSK) for the treatment of herpes. It is the first antiviral to be approved as a one-day treatment.

Two studies were conducted to prove efficacy. These studies included 1,856 patients with a history of herpes labialis. Patients were randomized to valacyclovir 2 g twice a day on day 1 and then a placebo on day 2; valacyclovir 2 g twice a day on day 1 and then valacyclovir 1 g twice on day 2; or placebo for both days.

Cold sores persisted for an average of 6.2 days in the placebo group compared to 5.2 days in the one-day valacyclovir treatment group (P<0.001 vs. placebo) and 5.4 days in the two-day valacyclovir treatment group (P<0.001 vs. placebo).

The most common adverse events associated with valacyclovir therapy were abdominal pain, nausea and headache. These data suggest that treatment with valacyclovir 2 g twice a day for one day significantly decreases the length of time for a cold sore outbreak by approximately one day, and subsequently has led to FDA approval for this treatment.

The FDA has recently approved valacyclovir one-day therapy for treatment of cold sores following data from clinical trials indicating a significant decrease in duration of outbreaks. Unfortunately oral valacyclovir, compared with other therapies available to treat cold sores, does not offer additional benefit in terms of time to resolution of lesions. However, valacyclovir has an advantage over other therapies by providing an oral one-day treatment instead of multiple day oral therapy or topical products that need to be applied numerous times each day. Valacyclovir for treatment of cold sores can provide shorter time to resolution of lesions, which is usually significant in terms of improving quality of life.

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