A new treatment for acne vulgaris combining benzoyl peroxide with clindamycin

Topical acne therapies are widely used for the treatment of mild to moderately severe acne vulgaris. However, many available treatments have limitations associated with their use, including lengthy time to response, cosmetic acceptability, and photosensitivity. Combinations of topical antibiotics and comedolytics are especially useful, but some formulations have stability challenges. A new combination formulation that contains 1% clindamycin and 5% benzoyl peroxide (BenzaClin Topical Gel) is currently available. In clinical trials, clinical improvement occurred at the first two follow-up visits and continued throughout treatment. In addition, combination therapy with clindamycin/benzoyl peroxide gel rapidly reduces Propionibacteria acnes counts and suppresses the emergence of clindamycin-resistant P. acnes. This formulation is stable at room temperature for up to 2 months after compounding. The aqueous gel vehicle is less drying, and there is no photosensitivity associated with its use. This study compares the combination treatment of 1% clindamycin and 5% benzoyl peroxide topical gel with other therapeutic options for mild to moderately severe acne vulgaris.     

Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial

Topical retinoids offer highly effective treatment for both inflammatory and non-inflammatory acne, with tazarotene demonstrating greater efficacy than other topical retinoids. A multicenter, double-blind, randomized, parallel-group trial has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl peroxide could enhance the efficacy of tazarotene still further. Patients with moderate to severe inflammatory acne applied tazarotene 0.1% cream each evening and were randomly assigned to morning applications of vehicle gel or a ready-to-dispense formulation of clindamycin 1%/benzoyl peroxide 5 % gel containing 2 emollients. Tazarotene/clindamycin/benzoyl peroxide achieved a significantly greater reduction in comedo count than tazarotene monotherapy and, among patients with a baseline papule plus pustule count of > or =25 (the median value), a significantly greater reduction in inflammatory lesion count. The combination therapy was also at least as well-tolerated as tazarotene monotherapy. The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability. Any improvements in tolerability could be due to the emollients in the clindamycin/benzoyl peroxide gel formulation.     

Clindamycin phosphate/tretinoin gel formulation in the treatment of acne vulgaris

Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. The main indication of CTG is the management of moderate comedonal and mild-to-moderate papulopustular acne, an acne form which is present in more than 50% of acne patients. CTG can also be combined with systemic antiacne therapy, such as systemic isotretinoin, in nodulocystic acne. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the well proven and beneficial comedolytic and anticomedogenic effects of tretinoin (all-trans retinoic acid). The addition of clindamycin to tretinoin enhances the comedolytic efficacy of tretinoin in moderate-to-severe acne of the face. The comedolytic activity of tretinoin and the anti-inflammatory efficacy of clindamycin accelerate resolution of all types of acne lesions without affecting the safety of both compounds. Discontinuation rates due to adverse events related to this formulation were found to be low (相似文献   

The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris

Clindamycin phosphate is the most widely used topical antibacterial agent for acne treatment. Treatment of patients with mild to moderate acne vulgaris with a new foam formulation (clindamycin foam, CF) for 12 weeks was at least as effective as clindamycin gel (CG) based on the Investigator's Static Global Assessment (ISGA) score. CF was superior to CG based on the reduction from baseline in total (P = .0014), inflammatory (P = .0478), and noninflammatory (P = .0037) acne lesion counts. Additionally, CF achieved efficacy that was superior to that of vehicle foam based on ISGA score (P = .0025) and all 3 lesion counts (all P < .05). Adverse experiences in the active treatment groups were mild or moderate and transient in nature. Thus the foam formulation of clindamycin is a safe and effective acne treatment; the unique foam delivery vehicle may offer cosmetic benefits to the patient and thus increase compliance.     

Clinical safety and efficacy studies of a novel formulation combining 1.2% clindamycin phosphate and 0.025% tretinoin for the treatment of acne vulgaris

Clindamycin phosphate 1.2% and tretinoin 0.025% gel (CLIN/RA gel [ZIANA Gel]) is a novel topical combination agent approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. A solution of clindamycin phosphate 1.2% combined with partially solubilized and crystalline tretinoin 0.025% suspended in an aqueous-based, alcohol-free gel formulation, CLIN/RA gel was studied in 2 randomized, vehicle-controlled trials involving more than 4,500 patients. Efficacy results from these studies showed that treatment with the combination significantly reduced lesion counts and improved patients' overall appearance to a greater extent than the individual components. Individual ingredients and the combination were well-tolerated. Among those treated with the combination formulation, discontinuation rates due to adverse events were 1% or less.     

Study results of benzoyl peroxide 5%/clindamycin 1% topical gel, adapalene 0.1% gel, and use in combination for acne vulgaris

Combination therapy is the standard of care in the management of acne vulgaris. It is essential to treat as many aspects of acne pathogenesis as possible. Due to increasing insensitivity of Propionibacterium acnes to antibiotics, the concomitant use of other topical agents that exhibit other modes of antibacterial and anti-inflammatory activity is integral to the successful treatment of acne. The combination of topical benzoyl peroxide and clindamycin gel has been shown to be more effective than either agent alone. The addition of a topical retinoid may further enhance therapeutic results. This 12-week study evaluated the safety and efficacy of initial topical benzoyl peroxide 5%/clindamycin 1% gel as monotherapy and in combination with adapalene gel versus adapalene gel monotherapy in the management of acne.     

Clindamycin phosphate/tretinoin gel formulation in the treatment of acne vulgaris

Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. The main indication of CTG is the management of moderate comedonal and mild-to-moderate papulopustular acne, an acne form which is present in more than 50% of acne patients. CTG can also be combined with systemic antiacne therapy, such as systemic isotretinoin, in nodulocystic acne. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the well proven and beneficial comedolytic and anticomedogenic effects of tretinoin (all-trans retinoic acid). The addition of clindamycin to tretinoin enhances the comedolytic efficacy of tretinoin in moderate-to-severe acne of the face. The comedolytic activity of tretinoin and the anti-inflammatory efficacy of clindamycin accelerate resolution of all types of acne lesions without affecting the safety of both compounds. Discontinuation rates due to adverse events related to this formulation were found to be low (≤ 1%). Safety of CTG use in pregnancy has not been established. The combination formulation is mainly designed to enhance effectiveness and minimize irritation. The once daily use of CTG, its rapid and dual effect and good tolerability have a positive impact on the duration of disease, patients' compliance and overall costs of therapy.     

Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris

Azelaic acid (AzA) 15% gel is approved for the treatment of rosacea in the US, but also has approval for the treatment of acne vulgaris in many European countries where it has demonstrated success. Two randomized, multicenter, controlled clinical trials compared the effects of AzA 15% gel with those of topical benzoyl peroxide 5% or topical clindamycin 1%, all using a twice-daily dosing regimen. The primary endpoint in the intent-to-treat analysis was a reduction in inflammatory papules and pustules. AzA 15% gel resulted in a 70% to 71% median reduction of facial papules and pustules compared with a 77% reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin. AzA 15% gel was well-tolerated. In addition, a 1-year European observational study conducted by dermatologists in private practice evaluated the safety and efficacy of AzA 15% gel used as monotherapy or in combination with other agents in more than 1200 patients with acne. Most physicians (81.9%) described an improvement in patients' symptoms after an average of 34.6 days, and 93.9% of physicians reported patient improvement after an average of 73.1 days. Both physicians and patients assessed AzA 15% gel to be effective with 74% of patients being "very satisfied" at the end of therapy. AzA 15% gel was considered "well-tolerated" or "very well-tolerated" by 95.7% of patients. The majority of patients were more satisfied with AzA than with previous therapies. AzA 15% gel represents a new therapeutic option for the treatment of acne vulgaris.     

An evaluation of dapsone gel 5% in the treatment of acne vulgaris

Background: Oral dapsone has been available for over 60 years. Its first clinical use was discovered in 1945, when it was found to be efficacious in inhibiting the progression of leprosy. The combined antibacterial and anti-inflammatory pharmacologic activities of dapsone have made it a widely investigated drug, particularly for use in refractory and unusual dermatologic conditions. However, the possibility of significant hematological side effects, even at low doses, has limited its use. Currently, oral dapsone has FDA approval for the treatment of leprosy and dermatitis herpetiformis. The potential of oral dapsone to treat acne vulgaris is well established, but the risks of serious side effects have made it an undesirable drug for use in the relatively healthy acne population. Recently, a topical formulation of dapsone (Aczone^?, Allergan, Inc., Irvine, CA, USA) has been approved by the FDA for the treatment of acne vulgaris. Objective/methods: The aims of this study were to review the published literature on dapsone pharmacology and pharmacokinetics, and to evaluate the gel's efficacy and safety in treating acne vulgaris, and finally to provide personal insight into its future as a topical agent for acne vulgaris. Results/conclusions: Clinical studies indicate dapsone gel 5% is effective in treating mild to moderately severe acne. It is well tolerated, with pharmacokinetic evidence indicating topical dosing in comparison to oral administration significantly reduces systemic concentrations of the drug, and therefore risk of serious side effects. Data suggests that dapsone gel 5% has the potential to become an established topical drug for the treatment of acne vulgaris. However, studies comparing the clinical effectiveness of the dapsone gel 5% to other available topical antiacne drugs are needed as are studies accessing its usefulness and safety when combined with other acne pharmaceuticals.     

Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study

In the treatment of mild to moderate acne vulgaris, the combination of an antibiotic and benzoyl peroxide provides enhanced efficacy over the individual agents, with the potential to decrease the emergence of resistant strains of P. acnes. To evaluate treatment regimens combining the daily use of a clindamycin/benzoyl peroxide gel, a tretinoin gel, and a clindamycin gel, the current randomized, evaluator-blind study was conducted. Results demonstrate that once-daily administration of clindamycin/benzoyl peroxide gel (combination formulation) was as effective as clindamycin/benzoyl peroxide gel + tretinoin gel + clindamycin gel. Both of these regimens provided greater efficacy than tretinoin + clindamycin. Treatment with clindamycin/benzoyl peroxide demonstrated a significant benefit over other treatments at Week 2, highlighting its rapid onset of action. All regimens were safe and generally well tolerated, with less severe peeling seen in patients who received clindamycin/benzoyl peroxide. In conclusion, the regimens that included clindamycin/benzoyl peroxide were more effective than tretinoin + clindamycin in the treatment of acne vulgaris, with no clinical advantage of adding tretinoin + clindamycin to once-daily clindamycin/benzoyl peroxide treatment.     

Safety and efficacy of micronized tretinoin gel (0.05%) in treating adolescent acne

Tretinoin is widely used in the treatment of acne. Despite significant advances in formulation development, irritation and dryness can be particularly bothersome, especially during the first 3-4 weeks, impacting adherence. Dose titration and adjunct use of moisturizers have been commonly employed. Co-prescribing with benzoyl peroxide (BPO) or a BPO/antibiotic combination is also common practice. The tretinoin molecule is unstable and can be degraded by BPO, further complicating treatment regimens. Lately, formulation technology has focused on providing more efficient penetration of the tretinoin into the skin layers so that lower concentrations of tretinoin might afford better tolerability, but maintain good efficacy; incorporating moisturizing excipients to minimize irritation; and providing greater stability to the tretinoin molecule. This approach would be particularly relevant in a pediatric acne population where efficacy/tolerability balance is important and treatment regimens must take into account lifestyles, but little data exist on the use of tretinoin in this patient population. A micronized formulation of tretinoin (0.05%) gel has been developed that provides a more efficient delivery of tretinoin, because of its optimal particle size, no degradation by BPO and better cutaneous tolerability than tretinoin microsphere (0.1%) gel without compromising efficacy in a pediatric population.     

Novel microemulsion-based gel formulation of tazarotene for therapy of acne

The objective of this study was to develop and evaluate a novel microemulsion based gel formulation containing tazarotene for targeted topical therapy of acne. Psudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and co-surfactant for microemulsion formation. The optimized microemulsion formulation containing 0.05% tazarotene was formulated by spontaneous microemulsification method consisting of 10% Labrafac CC, mixed emulsifiers 15% Labrasol–Cremophor–RH 40 (1:1), 15% Capmul MCM, and 60% distilled water (w/w) as an external phase. All plain and tazarotene-loaded microemulsions were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profiles of tazarotene through rat skin from optimized microemulsion formulation followed the Higuchi model for controlled permeation. Microemulsion-based gel was prepared by incorporating Carbopol®971P NF in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of tazarotene indicating its potential in improving its topical delivery. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.     

Topical Liposomal Gel of Tretinoin for the Treatment of Acne: Research and Clinical Implications

An attempt was made to pharmaceutically develop a topical liposomal tretinoin (TRE) gel and clinically evaluate the developed formulation for the treatment of acne in patients. Liposomes of TRE were prepared using the lipid film hydration technique and the entrapment efficiency of TRE in liposomes was optimized to 79.96%. The drug retention in liposomes and in liposomal TRE gel (Carbopol 934 gel base) studied at three storage conditions indicated maximum drug retention at refrigeration temperature. For liposomal TRE gel, reduced drug leakage was observed as compared to that of liposomes at all three storage conditions. Diffusion studies of plain TRE gel and liposomal TRE gel suggested prolongation (3.4 times reduction in flux value) of drug diffusion and almost two- fold increase in skin drug retention after liposomal encapsulation of drug. A comparative double-blind clinical study of the developed liposomal TRE gel, carried out on 30 acne patients over a period of 3 months, demonstrated significant enhancement (about 1.5-fold) in drug efficacy. More remarkable improvement was observed in the treatment of comedones, where the mean percent reduction in lesions increased from 62.36% for plain TRE gel to 94.17% for liposomal TRE gel. Erythema and irritation associated with the use of plain TRE gel was reduced considerably with the use of liposomal TRE gel. The findings of this investigation therefore underscore potential utility of commercialization of liposomal TRE gel in the treatment of acne.     

A multicenter clinical evaluation of the treatment of mild to moderate inflammatory acne vulgaris of the face with visible blue light in comparison to topical 1% clindamycin antibiotic solution

BACKGROUND: Blue light sources have been shown to be effective in the treatment of mild to moderate inflammatory acne vulgaris lesions. OBJECTIVE: We evaluated the safety and efficacy of a new blue light source in the treatment of mild to moderate inflammatory acne vulgaris in comparison to topical 1% clindamycin solution. RESULTS: Blue light therapy reduced inflammatory acne vulgaris lesions by an average of 34%, as compared to 14% for topical 1% clindamycin solution. CONCLUSIONS: The blue light source presented in this report is a safe and effective treatment option available to our patients with mild to moderate inflammatory acne lesions.     

Topical liposomal gel of tretinoin for the treatment of acne: research and clinical implications

An attempt was made to pharmaceutically develop a topical liposomal tretinoin (TRE) gel and clinically evaluate the developed formulation for the treatment of acne in patients. Liposomes of TRE were prepared using the lipid film hydration technique and the entrapment efficiency of TRE in liposomes was optimized to 79.96%. The drug retention in liposomes and in liposomal TRE gel (Carbopol 934 gel base) studied at three storage conditions indicated maximum drug retention at refrigeration temperature. For liposomal TRE gel, reduced drug leakage was observed as compared to that of liposomes at all three storage conditions. Diffusion studies of plain TRE gel and liposomal TRE gel suggested prolongation (3.4 times reduction in flux value) of drug diffusion and almost two-fold increase in skin drug retention after liposomal encapsulation of drug. A comparative double-blind clinical study of the developed liposomal TRE gel, carried out on 30 acne patients over a period of 3 months, demonstrated significant enhancement (about 1.5-fold) in drug efficacy. More remarkable improvement was observed in the treatment of comedones, where the mean percent reduction in lesions increased from 62.36% for plain TRE gel to 94.17% for liposomal TRE gel. Erythema and irritation associated with the use of plain TRE gel was reduced considerably with the use of liposomal TRE gel. The findings of this investigation therefore underscore potential utility of commercialization of liposomal TRE gel in the treatment of acne.     

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris

Context and objective: Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris.

Materials and methods: The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded.

Results: Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p?<?0.01), as well as Clin 2% or AA 5% treatment groups (p?<?0.05 or p?<?0.01). The percentage of reduction in ASI in combination treated group (64.16?±?6.01) was significantly more than those in the Clin 2% (47.73?±?6.62, p?<?0.05) and 5% AA (32.46?±?5.27, p?<?0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p?<?0.01). Seven patients in AA-Clin group (incidence?=?22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients.

Discussion and conclusion: The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.     

Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy?

Actinic keratoses (AKs) are common dysplastic epidermal lesions that share clinical, histologic, and molecular features with squamous cell carcinoma. Therapeutic options include destructive modalities (i.e., cryosurgery, curettage) or topical fluorouracil treatment. The efficacy of topical fluorouracil for the treatment of widespread AK lesions has been demonstrated in multiple studies, but treatment is often associated with significant skin irritation. Various approaches to decrease irritation while maintaining efficacy have been attempted, including altered treatment regimens, combination therapies, and variations in vehicle formulations. Recently, a novel topical fluorouracil cream that contains 0.5% 5-fluorouracil in a microsphere vehicle has been approved for the treatment of AK. Data demonstrate that this low-dose formulation is effective in reducing AK lesions while maintaining a tolerable irritation profile.     

Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T®). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL⁻¹) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL⁻¹. Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL⁻¹. The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake. Copyright © 1998 John Wiley & Sons, Ltd.     

Tolerability comparison of adapalene gel, 0.3% versus tazarotene cream, 0.05% in subjects with healthy skin

BACKGROUND: Topical retinoids, including adapalene and tazarotene, are a primary treatment choice for patients with acne. Adapalene is currently marketed in a 0.1% concentration in gel and cream formulation. A new gel containing a higher concentration (0.3%) of adapalene has been developed. In clinical studies, adapalene 0.1% concentration has proven to be better tolerated than other retinoids in skin treatment. However, the tolerability of adapalene gel 0.3% has yet to be compared to other topical retinoids. PURPOSE: The purpose of this study was to compare the local cutaneous tolerability of adapalene gel 0.3% once daily versus tazarotene cream 0.05% once daily. METHODS: Subjects reported to the investigative site each day Monday through Friday, cleansed the faced and then applied adapalene 0.3% gel to one side of the face and tazarotene 0.05% cream to the other in the presence of study personnel. For the weekends, subjects were instructed to apply the treatment at home according to the same procedure. Tolerability was assessed during each weekday visit. The study lasted for 3 weeks. RESULTS: Tolerability results for adapalene 0.3% gel and tazarotene 0.05% cream were statistically similar throughout the study. Investigator-assessed overall tolerability was in favor of adapalene at days 19 and 22 (P=.043). A cosmetic acceptability survey also showed results were better for adapalene 0.3% gel. CONCLUSION: Adapalene gel 0.3% is very well-tolerated with good cosmetic acceptability.