Valacyclovir: Clinical Studies on Herpes Labialis

Table of Content


Valacyclovir for Prevention of Recurrent Herpes Labialis: 2 Double-Blind, Placebo-Controlled Studies


  • The oral antiviral, valacyclovir, has three to five times more bioavailability than aciclovir and is an effective therapy to suppress recurrent herpes labialis lesions.
  • The efficacy of oral valacyclovir in the suppression of herpes labialis has not been reported earlier.
  • Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year.

  • Oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis.
  • In the valacyclovir group, 60% of patients were recurrence-free throughout the 4-month treatment period compared with only 38% patients in the placebo group (P= 0.041).
  • The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P= 0.016).
  • The total number of recurrences in patients using valacyclovir was 24 as compared with 41 in patients using placebo.
  • The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group as compared with the placebo group.

Cutis. 2003 Mar; 71(3):239-42

Suppressive Therapy versus Episodic Therapy with Oral Valacyclovir for Recurrent Herpes Labialis: Efficacy and Tolerability in an Open-Label, Crossover Study

  • This open-label, crossover study was conducted to evaluate the efficacy and tolerability of oral valacyclovir as suppressive therapy versus episodic therapy for recurrent herpes labialis.
  • Subjects with a history of at least 3 recurrent herpes labialis episodes in the past year were randomized to receive 6 months of oral valacyclovir episodic therapy at the first sign of prodrome (two 2-g doses separated by 12 hours) and 6 months of oral valacyclovir suppressive therapy (1 g once daily) for 6 months.
  • The mean number of recurrences per 120 days of follow-up (primary endpoint) was lower with suppressive therapy than episodic therapy (P < 0.005).
  • Suppressive therapy with oral valacyclovir was more effective than episodic therapy with oral valacyclovir in reducing the frequency of recurrences of herpes labialis and prolonging the time to first recurrence and was also similarly well -tolerated.
  • The probability of remaining recurrence free over 6 months was significantly higher with suppressive therapy than episodic therapy. The median time to first recurrence was 81 days with episodic therapy and was not calculable (> 180 days) for suppressive therapy (P = 0.021).
  • The data for secondary efficacy endpoints (pain severity score, mean duration of recurrences, maximal total lesion area) showed approximately a 30% to 50% reductions in mean values with suppressive therapy compared with episodic therapy, but the results were statistically significantly different between the regimens for pain severity only.
  • The percentage of subjects with at least one drug-related adverse event over 6 months of treatment was 3% with suppressive therapy and 6% with episodic therapy.

J Drugs Dermatol. 2007; 6(4):400- 5

Valacyclovir for Herpes Labialis

  • The treatment of herpes simplex labialis has been associated with modest benefits and this difficulty results from the rapid resolution of the disease accomplished by the immune system, which narrows the window of therapeutic opportunity.
  • The immune response is also responsible for important clinical manifestations such as oedema and pain.
  • The dual role of immune responses (protection, pathology) is well recognized in other infectious diseases. The addition of corticosteroids to antimicrobial agents has been associated with improvement in some of these diseases.
  • The authors evaluated the combination of oral valacyclovir plus topical clobetasol compared with placebo for recurrent herpes simplex labialis.
  • A total of 81 subjects were screened, randomized, and dispensed valacyclovir 2 g orally twice daily for 1 day and clobetasol gel 0.05% twice daily for 3 days). A recurrence developed in 42 patients and treatment was re-initiated.
  • There were 50% of aborted lesions in the valacyclovir-clobetasol arm compared with 15.8% in the placebo arm (P = 0.04). The combination therapy reduced the mean maximum lesion size from 54 mm2 to 9.7 mm2 (P=0.002). The mean healing time of classical lesions was reduced to 5.8 days by the combination therapy as compared with 9.3 days with placebo (P=0.002).
  • The addition of topical corticosteroids to an oral antiviral agent for the treatment of herpes simplex labialis is supported through this study.
  • Reduction in the area under the curve of classical lesion size versus time was observed in the combination arm as compared with placebo (P<0.001). Adverse events noted were minimal.
  • Secondary and post-treatment recurrences were not increased by combination therapy.

J Eur Acad Dermatol Venereol. 2009; 23(3): 263-7