Treatment Of Recurrent Herpes Labialis Research Articles

Topical treatment of recurrent herpes labialis

Topical treatment of recurrent herpes labialis

Effects of antiviral usage on transmission dynamics of herpes simplex virus type 1 and on antiviral resistance: predictions of mathematical models.

Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.

A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis

Background: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. Objective: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. Methods: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. Results: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 ± 0.27 days for the placebo group and 2.3 ± 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 ± 0.36 days for the placebo group and in 5.1 ± 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant ( P = .0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 ± 0.6; active index, 7.3 ± 0.48 [ P = .0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 ± 0.28 for active on a scale in which 1.0 represented “no pain at all” and 10 represented “most severe pain imaginable.” Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. Conclusion: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect. (J Am Acad Dermatol 1999;41:996-1001.)

A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis

In a 2-armed, double-blind, randomized clinical study, the efficacy in the treatment of recurrent herpes labialis of 5% acyclovir in a novel liposomal carrier (ethosome) was evaluated in comparison with that of a commercial 5% acyclovir cream (Zovirax cream) and that of a drug-free vehicle. Data were based on 61 herpetic episodes in 40 subjects. In a crossover arm in which the 2 active preparations were compared, the time to crusting of lesions was significantly shorter ( P < .025) with the ethosomal acyclovir (1.8 days) than with the cream (3.5 days). Time to loss of crust was also significantly shorter (4.2 vs 5.9 days; P < .05). In a parallel arm in which all 3 preparations were compared, the time to crusting with the ethosomal acyclovir (1.6 days) was significantly shorter than the time with the acyclovir cream (4.3 days; P < .02) and the time with the drug-free vehicle (4.8 days; P < .005); in this arm, the shorter time to loss of crust for the ethosome (3.5 days), in comparison with the times for the cream (6.4 days) and the drug-free vehicle (6.1 days), did not reach statistical significance. Approximately 30% of all episodes treated with the ethosome were clinically abortive; this compared with 10% of those treated with the cream or the drug-free vehicle. No adverse effects were reported, other than minor burning sensations at the application site that lasted a few seconds after application and were evenly distributed between the investigated preparations. This pilot study suggests the improved clinical efficacy of the new liposomal preparation in comparison with Zovirax cream in the treatment of recurrent herpes labialis. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:700-5)

Efficacy of 86C (acyclovir) cream 5% compared with Zovirax® (acyclovir) cream 5% in the treatment of recurrent herpes labialis

This double-blind, crossover, Phase III study compared 86C (acyclovir) cream 5% with Zovirax® (acyclovir) cream 5% in patients with recurrent herpes labialis. Both in vitro skin penetration tests and a guinea pig skin model infected with herpes simplex virus type 1 have shown a significantly shorter healing time with 86C than with Zovirax. The aim of our study was to establish if this difference could be confirmed in patients suffering from recurrent herpes labialis. The patients had to experience two complete attacks of herpes labialis during the study, and were instructed to start the antiviral treatment at the very early prodromal symptoms and each attack. Cream was applied to the lesion five times daily for 5 days. Results of 59 assessable patients showed no significant difference between the two cream formulations. The number of half days to healing was 10.47 for 86C and 10.12 for Zovirax. A total of 20 patients preferred 86C, 26 patients preferred Zovirax, and 13 patients had no drug preference. Both drugs were shown to be efficacious and safe. No adverse events occurred in this study.

Looking for healthy volunteers

Topical aciclovir cream (ACV, Zovirax Cream) containing 40% propylene glycol (PG), the optimum found for skin penetration, is clinically effective in the treatment of recurrent herpes labialis. One hundred and thirty-nine ACV generic creams were analysed and 80% of these contained less than 20% PG. From this, we hypothesised that these generics might be bioinequivalent to the innovator cream. A pilot in vitro skin permeation study compared the innovator cream with two generics containing about 15% PG. Next, 10 generics containing 0–15% PG were tested in an independent laboratory. Finally, a PG dose-ranging study was conducted in Zovirax cream base. In all studies, human skin was used and ACV analysed by LC-MS-MS. In the pilot study, the innovator cream delivered 7.5-fold more ACV than the two generics. Superiority was confirmed in the second study against all 10 ACV generic creams. By grouping the creams according to PG content, a relationship to ACV skin permeation was suggested. The PG dose effect was confirmed in the third study. These studies suggest that not all marketed ACV creams are bioequivalent to the clinically proven innovator. Given the magnitude of the differences seen, there is concern over therapeutic inequivalence of generic ACV creams to the innovator cream.

75 n-Docosanol cream is an effective topical treatment of recurrent herpes labialis : DAVID H. KATZ∗, LIDAK Pharmaceuticals, La Jolla, CA, U.S.A, L. HABBEMA, Academisch Ziekenhuis Rotterdam Dijkzigt, Rotterdam, The Netherlands, K. DE BOULLE, Aalst, Belgium, G.A. RODERS, Brocades Pharma BV, Leiderdorp, The Netherlands

75 n-Docosanol cream is an effective topical treatment of recurrent herpes labialis : DAVID H. KATZ∗, LIDAK Pharmaceuticals, La Jolla, CA, U.S.A, L. HABBEMA, Academisch Ziekenhuis Rotterdam Dijkzigt, Rotterdam, The Netherlands, K. DE BOULLE, Aalst, Belgium, G.A. RODERS, Brocades Pharma BV, Leiderdorp, The Netherlands

Herpes labialis treatment with acyclovir 5% modified aqueous cream: A double-blind, randomized trial

The efficacy of 5% acyclovir in a modified aqueous cream vehicle (ACV-MAC) in the treatment of recurrent herpes labialis was tested in a randomized, double-blind clinical trial with the modified aqueous cream vehicle as a control medication. The ACV-MAC formulation has previously been shown to offer superior cutaneous absorption relative to other topical acyclovir formulations. Treatment was initiated by patients within 1 hour of prodrome in an attempt to maximize clinical impact of this virustatic drug. While the patient group receiving active drug showed a trend toward accelerated healing, no significant differences for lesion or healing characteristics could be measured between the two treatment groups. It is suggested that optimal efficacy of ACV-MAC may be predicated on prophylactic treatment, that is, “trigger”-initiated rather than prodrome-initiated treatment.

Adenosine in the treatment of recurrent herpes labialis

The effectiveness of adenosine 5′-monophosphate was tested in thirty-six patients with recurrent herpes labialis. The compound displayed an immediate effect upon the healing of the recurrent lesions. Furthermore, twenty-three patients were free of recurrences for varying intervals extending over 2 years. In the remainder of the treated patients, a single recurrent episode was observed.

A Double-Blind, Controlled Trial of Levamisole in the Treatment of Recurrent Herpes Labialis

A double-blind, controlled trial of levamisole in the prevention and treatment of recurrent cold sores was performed. Forty-eight subjects received levamisole in a dosage of 2.5 mg/kg on two consecutive days each week for six months. The 51 control subjects were given a placebo identical to the drug in appearance. Both groups were given the same instructions. Nineteen subjects receiving levamisole and eight receiving placebo withdrew during the six months of the study. There were no significant differences between the levamisole-treated and control groups in the duration or severity of the lesions during the trial period or in the subjective assessment of drug efficacy by the participants at the end of the trial. Before treatment the frequency of lesions in the levamisole group was higher than in the control group. Only when this factor was taken into account by analysis of covariance did the decreased frequency of lesions during therapy appear significantly lower in the group receiving levamisole than in the placebo group. The difference remained clinically unimpressive. This study does not support earlier suggestions that levamisole, in these doses, is useful in the treatment of recrudescent circumoral herpesvirus infections.

The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis

The efficacy of a water-soluble bioflavonoid-ascorbic acid complex was evaluated in the treatment of fifty episodes of recurrent herpes labialis. Twenty episodes were treated with a complex of 600 mg. of water-soluble bioflavonoids and 600 mg. of ascorbic acid, administered in equal increments three times daily. Twenty episodes were treated with a complex of 1,000 mg. of water-soluble bioflavonoids and 1,000 mg. of ascorbic acid, administered in equal increments five times daily. Ten episodes were treated with a lactose placebo. The therapeutic regimen was maintained for 3 days after the recognition of the initial symptoms associated with recurrent herpes labialis. The water-soluble bioflavonoid-ascorbic acid complex was observed to reduce vesiculation and to prevent the disruption of the vesicular membrane. The therapeutic measure was found to be most effective when initiated during the prodromal stage of the disease process. Optimum remission of symptoms was observed in 4.2 ± 1.7 days with the 600 mg. dosage of the water-soluble bioflavonoid-ascorbic acid complex. No adverse reactions were reported by any of the patients who participated in this investigation.