Treatment of Recurrent Herpes Simplex Labialis with Oral Acyclovir

Spruance, Spotswood L.; Stewart, James; Rowe, Nathaniel H.; McKeough, Mark B.; Wenerstrom, G.; Freeman, Donna J.

doi:10.1093/infdis/161.2.185

Cited by 142 publications

(59 citation statements)

References 3 publications

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“…Two studies, one using topical acyclovir cream and one using oral acyclovir, have shown some apparent effect on the prevention of cold sore lesion progression (6,16). However, these results have not been reproduced in subsequent studies (14,19,21). The present valacyclovir studies are the two largest, placebo-controlled trials of herpes labialis treatment designed to test the hypothesis that the progression of cold sore lesions could be prevented with oral medication if taken early (i.e., at the first symptoms).…”

Section: Discussionmentioning

confidence: 88%

“…This difference as well as other measures of clinical healing was not statistically significant. Spruance et al evaluated a regimen of 400 mg of oral acyclovir 5 times daily for 5 days in comparison with placebo (21). Overall in this study, acyclovir did not affect the duration of the episode, mean maximum lesion size, or the development of lesions, but a subset of early treated patients achieved a 36% mean reduction in pain (P ϭ 0.02) and a 27% mean reduction in time to lesion healing (P ϭ 0.03).…”

mentioning

confidence: 77%

“…The valacyclovir 1-day treatment regimen of 2 g twice daily was expected to provide a peak acyclovir concentration of approximately 8 g/ml and a concentrationtime profile in excess of the 99% inhibitory concentration of 4.21 g/ml for approximately 5.5 h (ϳ23%) during the first 24-h period (3,17,24). A single-day valacyclovir regimen of 2 g (14,16,21). It is presumed, but not proven, that a strong antiviral effect hastens wound resolution by decreasing the extent of keratinocyte destruction, the viral antigen load, and the attendant inflammatory response, which impair reepithelization at the site of infection (1,9,11,22).…”

Section: Discussionmentioning

confidence: 99%

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High-Dose, Short-Duration, Early Valacyclovir Therapy for Episodic Treatment of Cold Sores: Results of Two Randomized, Placebo-Controlled, Multicenter Studies

Spruance

Jones

Blatter

et al. 2003

Antimicrob Agents Chemother

102

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Oral valacyclovir is better absorbed than oral acyclovir, increasing acyclovir bioavailability three-to fivefold. This provides the opportunity to explore whether high systemic acyclovir concentrations are effective in the treatment of cold sores (herpes labialis). Two randomized, double-blind, placebo-controlled studies were conducted. Subjects were provided with 2 g of valacyclovir twice daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day treatment), or a matching placebo and instructed to initiate treatment upon the first symptoms of a cold sore. In study 1, the median duration of the episode (primary endpoint) was reduced by 1.0 day (P ‫؍‬ 0.001) with 1-day treatment and 0.5 days (P ‫؍‬ 0.009) with 2-day treatment compared to placebo. Similarly, the mean duration of the episode was statistically significantly reduced by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment compared to placebo. The proportion of subjects in whom cold sore lesion development was prevented and/or blocked was increased by 6.4% (P ‫؍‬ 0.096) with 1-day treatment and 8.5% (P ‫؍‬ 0.061) with 2-day treatment compared to placebo. The time to lesion healing and time to cessation of pain and/or discomfort were statistically significantly reduced with valacyclovir compared to placebo. In study 2, results similar to those in study 1 were obtained. AEs were similar across treatment groups. These studies provide evidence supporting a simple, 1-day valacyclovir treatment regimen for cold sores that is safe and effective. The 1-day valacyclovir regimen offers patients a unique and convenient dosing alternative compared to available topical therapies.Herpes labialis, or cold sores, are caused by herpes simplex virus type 1 (HSV-1) and can result in significant irritation, pain, discomfort, and worry (18,25). The infection is most often acquired in childhood, but the incidence increases with age (2, 5, 12, 18). Up to 90% of persons over the age of 50, depending on race, sex, and country, would test seropositive for HSV-1, and an estimated 20 to 40% of adults experience cold sore outbreaks (5,12,18,25).Until now, most treatments have consisted of creams that must be applied to affected areas multiple times a day for several days (6,13,15,19,20,23). There have been two previous clinical trials of oral antiviral therapy for episodic treatment of herpes labialis. In a double-blind, placebo-controlled trial involving 210 subjects with recurrent cold sores, it appeared that less time was required for the loss of hard crust for subjects taking 200 mg of oral acyclovir 5 times daily for 5 days (14). This difference as well as other measures of clinical healing was not statistically significant. Spruance et al. evaluated a regimen of 400 mg of oral acyclovir 5 times daily for 5 days in comparison with placebo (21). Overall in this study, acyclovir did not affect the duration of the episode, mean maximum lesion size, or the development of lesions, but a subset o...

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High-Dose, Short-Duration, Early Valacyclovir Therapy for Episodic Treatment of Cold Sores: Results of Two Randomized, Placebo-Controlled, Multicenter Studies

Spruance

Jones

Blatter

et al. 2003

Antimicrob Agents Chemother

102

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“…This concept received support from two prior clinical trials with peroral ACV and topical idoxuridine in dimethyl sulfoxide which showed that antiviral nucleoside efficacy was limited to the patients who initiated treatment in the prodrome or erythema lesion stage (18,19). One potential explanation for the discrepancy between the peroral ACV and topical idoxuridine in dimethyl sulfoxide studies on the one hand and the penciclovir and ACV cream trials on the other is that the delivery of drug to the site of virus replication was far more efficient by the oral route of administration and from the dimethyl sulfoxide vehicle than from the cream vehicles (14).…”

Section: Discussionmentioning

confidence: 99%

“…ACV (5%) ointment (Zovirax ointment) accelerated healing of herpes labialis in immunocompromised patients (22). Peroral administration of 400 mg of ACV five times/day for 5 days significantly reduced virus shedding and reduced lesion healing time and the duration of lesion pain among the subgroup of patients who started treatment "early" (in the prodrome or erythema lesion stage) (19). Peroral ACV administered as prophylaxis at 400 mg two times/day significantly reduces the frequency of recurrent episodes and prevents herpes-associated erythema multiforme (4,8,11).…”

mentioning

confidence: 99%

Acyclovir Cream for Treatment of Herpes Simplex Labialis: Results of Two Randomized, Double-Blind, Vehicle-Controlled, Multicenter Clinical Trials

Spruance

Nett

Marbury

et al. 2002

Antimicrob Agents Chemother

122

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Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] ‫؍‬ 1.23; 95% confidence interval [CI], 1.06 to 1.44; P ‫؍‬ 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR ‫؍‬ 1.24; 95% CI, 1.06 to 1.44; P ‫؍‬ 0.006). Efficacy was apparent whether therapy was initiated "early" (prodrome or erythema lesion stage) or "late" (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.Acyclovir (ACV) has been found to be efficacious in the management of herpes labialis in a variety of formulations and routes of administration. ACV (5%) ointment (Zovirax ointment) accelerated healing of herpes labialis in immunocompromised patients (22). Peroral administration of 400 mg of ACV five times/day for 5 days significantly reduced virus shedding and reduced lesion healing time and the duration of lesion pain among the subgroup of patients who started treatment "early" (in the prodrome or erythema lesion stage) (19). Peroral ACV administered as prophylaxis at 400 mg two times/day significantly reduces the frequency of recurrent episodes and prevents herpes-associated erythema multiforme (4,8,11).Demonstration of the clinical efficacy of topical formulations of antiviral drugs among immunocompetent patients has been difficult because of the marked variance in lesion severity that occurs, necessitating large numbers of subjects; the rapid natural healing of lesions; and the difficulty in finding a topical drug formulation that facilitates skin penetration without causing undue skin irritation (15,16,20). Several studies with ACV ointment in immunocompetent subjects provided sparse evidence of efficacy in this population (1,6,13,17). ACV was shown to penetrate human skin more effectively in a cream than in an ointment formulation (3). According...

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