Penciclovir Cream Research Articles

Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

Comparison of topical acyclovir and penciclovir in recurrent herpes labialis treatment

Purpose: The aim of this study is to compare the effects of acyclovir and penciclovir creams in the treatment of recurrent herpes labialis. 
 Materials and Methods: Seventy patients with pre-diagnosed recurrent herpes labialis lesions were enrolled in this study. Diagnosis was confirmed with HSV-1 IgM antibody test. Patients were separated under 2 treatment groups as acyclovir and penciclovir cream. Both agents were applied until complete healing of the lesions was seen. Burning, itching and bleeding scores; time of erythema, vesicles, ulceration, crusting and crust loss of the lesions were recorded. Pain values of the patients were recorded using a visual analog scale (VAS) and DASS-21 scale was used to measure emotional state related to depression, anxiety and stress. 
 Results: Pain level in the acyclovir group was significantly lower than the penciclovir group in the 3rd day, though with no difference in the following days. DASS-21 scores revealed signs of depression on 62.8% of the patients, anxiety on 34.2% of the patients, and stress on 41.4% of the patients in moderate or higher levels. While the pain level was higher in patients with high anxiety severity, it was observed that the pain level was low in patients with high stress intensity.
 Conclusion: Although it is not possible to cure recurrent herpes labialis completely, any methods and drugs that shorten the healing time of the lesion and reduce pain and discomfort gains importance. Our study showed that acyclovir is superior in reducing pain.

Oral gel loaded with penciclovir–lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

LABORATORY EQUIPMENT DURING PHARMACEUTICAL DEVELOPMENT OF SEMI-SOLID PREPARATIONS

Introduction. When developing drugs it is necessary to use laboratory equipment that simulates pilot and industrial equipment. For the production of semi-solid preparations the key equipment are rotor-stator dispersers and vacuum reactors-homogenizers. Aim. Investigation of the functional characteristics of laboratory equipment: Megatron® MT 1-50 dispersant SHS F/2 (Kinematica AG, Switzerland) and the RP-5 vacuum homogenizer reactor (Promvit, Ukraine). Materials and methods. During development a generic product Penciclovir cream 1% the initial particle size in suspension of penciclovir and particle size after grinding were studied by optical microscopy and laser diffraction methods. In a cream made in the reactor, the particle size of the dispersed phase of the o/w emulsion and suspension, as well as the absence of air bubbles, were determined by optical microscopy. The assay of penciclovir in 9 samples of the cream taken from the reactor-homogenizer was performed by liquid chromatography. By the of rotational viscometry method the rheological properties of the cream were studied. By the inductively coupled plasma atomic emission spectroscopy the getting of metal impurities from the disperser and the reactor-homogenizer into the suspension and cream were investigated. Results and discussion. With an increase in the rotor speed, the particle size of penciclovir in suspension decreases. The disperser effectively performs its function at a rotor speed of 25,000 rpm. In a cream made in the reactor, the deviations in the quantitative content of penciclovir from the average value in each sample are within the uncertainty of the analytical procedure, which indicates its uniform distribution. The reactor provides effective dispersion and uniform distribution of the oil phase, prevents the formation of a gas emulsion and allows getting a cream that, according to its rheological properties, corresponds to the reference preparation Fenistil® Pencivir cream 1%. In the production process metal impurities were not emitted into the suspension and the cream from the equipment. Conclusion. The disperser and the reactor during the production of cream with penciclovir are suitable for their intended use. It is rational to combine these two types of equipment at the sites for the production of semi-solid preparations. The disperser can also be used to produce emulsions with a very small particle size of the dispersed phase.

Herpes Labialis: An Update.

Herpes labialis is characterized by recurrent vesicular eruptions primarily on the lips and perioral skin. The condition is contagious, can cause significant discomfort/pain, and can have an adverse effect on the quality of life. To update the evaluation and treatment of herpes labialis. A PubMed search was completed in Clinical Queries using the key term "herpes labialis". Patents were searched using the key term "herpes labialis" from www.freepatentsonline.com. The diagnosis of herpes labialis is mainly clinical based on classic grouped lesions (papules, vesicles, ulcers) on the lip. Antiviral therapy shortens the duration of pain and discomfort, hastens healing, and reduces viral shedding. Thus, episodic treatment is warranted, especially if the patient desires treatment for cosmetic purposes or for relief of pain. Such treatment needs to be initiated promptly, ideally in the prodromal stage and no later than 48 hours from the onset of lesions to achieve optimal results. Chronic suppressive therapy with oral antiviral agents should be considered for patients with severe or frequent (six or more episodes per year) recurrences. Recent patents related to the management of herpes labialis are also discussed. For episodic treatment, oral antiviral agents, such as acyclovir (Zovirax), valacyclovir (Valtrex) and famciclovir (Famvir), are superior to topical antiviral therapy. Valacyclovir and famciclovir have greater oral bioavailability and are better absorbed than acyclovir, require less frequent dosing, but are more expensive and are not approved for children. Topical antiviral agents such as 5% acyclovir cream/ointment (Zovirax) ± hydrocortisone (Xerese), 1% penciclovir (Denavir) cream, and 50 mg Buccal Adhesive Tablet (ABT-50 mg) can also be used for episodic treatment of herpes labialis. These topical agents are not effective in the prevention of recurrent herpes labialis. For chronic daily suppressive therapy, oral antivirals are the treatment of choice.

A new topical treatment protocol for oral hairy leukoplakia

The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA). Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model. Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively. The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.

Effective treatment of herpes simplex labialis with penciclovir cream: Combined results of two trials

Two randomized, double-blind, parallel-group clinical trials were conducted in Europe and North America to compare the efficacy and safety of topical 1 percent penciclovir cream with a placebo cream. A total of 4,573 immunocompetent people with a history of recurrent herpes simplex labialis, or HSL, with three or more episodes a year that typically manifested as classical lesions, were enrolled and prospectively dispensed medication-either 1 percent penciclovir in a cetomacrogol cream base or a matching placebo. Patients self-initiated treatment and were required to apply study medication six times per day for the first day and every two hours while awake for four consecutive days. Of 4,573 enrolled patients, 3,057 initiated treatment (1,516 with penciclovir and 1,541 with placebo). Combined data from two trials revealed that penciclovir recipients lost classical lesions 31 percent faster than did placebo recipients (hazard ratio, or HR, = 1.31; 95 percent confidence interval, or CI, 1.20 to 1.42; P = .0001) and experienced 28 percent faster resolution of lesion pain (HR = 1.28; 95 percent CI, 1.17 to 1.39; P = .0001). Significant benefits were achieved with penciclovir use whether treatment was initiated in the early stages (P = .001) or later stages (P = .0055). The largest data set currently available on the treatment of recurrent HSL revealed that penciclovir cream significantly outperformed the placebo in healing classical lesions and resolution of pain. The authors found that penciclovir cream positively affects recurrent HSL, and dose frequency is vital to topical treatment. Even when penciclovir was applied late, it was effective in favorably altering the course of recurrent HSL.

Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial

BACKGROUND : Herpes simplex facialis/labialis (HSFL) is a common infectious skin disorder, caused mainly by herpes simplex virus (HSV) type 1, for which the topical application of a cream containing an antiviral agent for treatment of the disease has been widely utilized. OBJECTIVE : To explore the efficacy of the topical application of 1% penciclovir cream in the treatment of HSFL, and to compare its efficacy and safety with 3% aciclovir cream. METHODS : A total of 248 patients with a diagnosis of HSFL were randomly allocated to one of the two treatment groups ( n = 124 each), using stratified randomization based on a table of random numbers. Before treatment (day 0) and at every visit (days 3, 5 and 7) during the study, the sign and symptom scores were recorded by the same doctor. RESULTS : Excluding 23 patients (10 in the penciclovir and 13 in the aciclovir groups), 225 completed the study, and no severe adverse events were noted with any of the treatment regimens. Results show that an encouraging improvement in the clinical course was found simultaneously for patients with each episode type and each treatment assignment. There were no significant differences in terms of efficacy endpoint, clinical cure rate, and safety between the two treatment arms, but there was a trend towards a shorter time to resolution of all symptoms, cessation of new blisters, and loss of crust ( p h 0.08) in penciclovir-treated primary patients. In addition, the clinical scores in penciclovir-treated primary patients were significantly lower than those in the respective aciclovir-treated patients on treatment day 5 ( p < 0.01) and day 7 ( p < 0.05). CONCLUSION : Topical 1% penciclovir cream is as convenient and as effective as 3% aciclovir cream for the treatment of HSFL. Penciclovir cream may provide a good topical alternative to other types of therapy in the future.

Penciclovir cream for the treatment of sunlight-induced herpes simplex labialis: A randomized, double-blind, placebo-controlled trial

The purpose of this study was to further define the therapeutic value of penciclovir cream in the treatment of sunlight-induced herpes labialis by comparing its efficacy and tolerability with those of an inactive control (purified water). In this randomized, double-blind, placebo-controlled, parallel-group clinical trial, lesions were induced by exposure to sunlight. Treatment was self-initiated within 1 hour of development of the signs or symptoms of a recurrence. Healthy male and female patients (mean age, 38.3 years; range, 18 to 81 years) who had a history of sunlight-induced herpes labialis (mean of 6 recurrences in previous 12 months) applied either penciclovir cream (n = 266) or purified water (n = 275). Penciclovir cream significantly decreased the time to lesion healing (P < 0.001), with a reduction in median time of up to 2 days. The efficacy of penciclovir cream was further supported by a significant reduction in maximum lesion area (P = 0.008), a faster loss of lesion-associated symptoms (P = 0.026), and significant reductions in daily assessments of pain (P < or = 0.040), itching (P < or = 0.032), burning (P < or = 0.028), and tenderness (P < or = 0.026) as moderate or severe. These effects were reinforced by the results of the daily self-assessment of lesion attributes, with significantly fewer severe/extreme assessments of lesion size (P < or = 0.003), noticeability (P < or = 0.003), amount of scab/crust (P < or = 0.003), raised/ swollen area (P < or = 0.040), soreness/tenderness (P < or = 0.043), and overall severity (P < or = 0.001) throughout the study period. Penciclovir cream has demonstrated efficacy for a broad range of clinically important outcomes. Significant effects on lesion area, lesion symptoms, and other lesion attributes extend the clinical efficacy of penciclovir cream beyond lesion healing.

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.)

Penciclovir cream for the treatment of herpes simplex labialis: A randomized, multicenter, double-blind, placebo-controlled trial: Spruance SL, Rea TL, Thoming C, et al. JAMA 277:1374, 1997

Penciclovir cream for the treatment of herpes simplex labialis: A randomized, multicenter, double-blind, placebo-controlled trial: Spruance SL, Rea TL, Thoming C, et al. JAMA 277:1374, 1997

Penciclovir Cream for the Treatment of Herpes Simplex Labialis

<h3>Objective.</h3> —To compare the safety and efficacy of topical 1% penciclovir cream with vehicle control cream (placebo) for the treatment of a recurrent episode of herpes simplex labialis (cold sores) in immunocompetent patients. <h3>Design.</h3> —Randomized, double-blind, placebo-controlled, patient-initiated, 2-armed, parallel clinical trial. Patients were prospectively dispensed study medication, and treatment was self-initiated by the patient within 1 hour of the first sign or symptom of a recurrence. <h3>Setting.</h3> —A total of 31 ambulatory clinics in the United States in a variety of settings, including private practices, public health facilities, and universities. <h3>Patients.</h3> —Otherwise healthy individuals with a history of frequent episodes of herpes simplex labialis. A total of 2209 patients were enrolled and given study medication, and 1573 initiated treatment for a recurrence. <h3>Interventions.</h3> —Topical 1% penciclovir cream or vehicle control cream. Subjects applied treatment every 2 hours while awake for 4 consecutive days. <h3>Main Outcome Measures.</h3> —Lesion healing was the primary efficacy variable. Secondary end points included time to loss of lesion pain and time to cessation of viral shedding. <h3>Results.</h3> —Healing of classical lesions (vesicles, ulcers, and/or crusts) was 0.7 day faster for penciclovir-treated patients compared with those who received vehicle control cream (median, 4.8 days vs 5.5 days; hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.49;<i>P</i>&lt;.001). Pain (median, 3.5 days vs 4.1 days; HR, 1.22; 95% CI, 1.09-1.36;<i>P</i>&lt;.001) and lesion virus shedding (median, 3 days vs 3 days; HR, 1.35; 95% CI, 1.10-1.64;<i>P</i>=.003) also resolved more quickly for penciclovir-treated patients compared with patients who applied the vehicle control. The efficacy of penciclovir cream was apparent when therapy was initiated early (prodrome or erythema lesion stage) and when initiated late (papule or vesicle stage). The incidence of adverse events was comparable between penciclovir and placebo groups. <h3>Conclusions.</h3> —Penciclovir cream is the first treatment to clearly demonstrate an impact on the course of recurrent herpes labialis in immunocompetent patients. Efficacy was seen in all clinical and laboratory measures of the disease (lesion healing, pain resolution, and cessation of viral shedding). Faster healing and pain resolution occurred both among patients who first applied penciclovir cream in the prodrome and erythema stages and among those who started treatment in the papule and vesicle lesion stages.

Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group

To compare the safety and efficacy of topical 1% penciclovir cream with vehicle control cream (placebo) for the treatment of a recurrent episode of herpes simplex labialis (cold sores) in immunocompetent patients. Randomized, double-blind, placebo-controlled, patient-initiated, 2-armed, parallel clinical trial. Patients were prospectively dispensed study medication, and treatment was self-initiated by the patient within 1 hour of the first sign or symptom of a recurrence. A total of 31 ambulatory clinics in the United States in a variety of settings, including private practices, public health facilities, and universities. Otherwise healthy individuals with a history of frequent episodes of herpes simplex labialis. A total of 2209 patients were enrolled and given study medication, and 1573 initiated treatment for a recurrence. Topical 1% penciclovir cream or vehicle control cream. Subjects applied treatment every 2 hours while awake for 4 consecutive days. Lesion healing was the primary efficacy variable. Secondary end points included time to loss of lesion pain and time to cessation of viral shedding. Healing of classical lesions (vesicles, ulcers, and/or crusts) was 0.7 day faster for penciclovir-treated patients compared with those who received vehicle control cream (median, 4.8 days vs 5.5 days; hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.49; P<.001). Pain (median, 3.5 days vs 4.1 days; HR, 1.22; 95% CI, 1.09-1.36; P<.001) and lesion virus shedding (median, 3 days vs 3 days; HR, 1.35; 95% CI, 1.10-1.64; P=.003) also resolved more quickly for penciclovir-treated patients compared with patients who applied the vehicle control. The efficacy of penciclovir cream was apparent when therapy was initiated early (prodrome or erythema lesion stage) and when initiated late (papule or vesicle stage). The incidence of adverse events was comparable between penciclovir and placebo groups. Penciclovir cream is the first treatment to clearly demonstrate an impact on the course of recurrent herpes labialis in immunocompetent patients. Efficacy was seen in all clinical and laboratory measures of the disease (lesion healing, pain resolution, and cessation of viral shedding). Faster healing and pain resolution occurred both among patients who first applied penciclovir cream in the prodrome and erythema stages and among those who started treatment in the papule and vesicle lesion stages.