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   

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.     

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.     

Benzoyl peroxide microsphere cream as monotherapy and combination treatment of acne

This office-based case series describes the use of a new formulation of benzoyl peroxide (BPO) delivered via a porous microsphere cream vehicle in patients with mild to moderate acne vulgaris. While BPO has been used for many years as antimicrobial in the treatment of acne, in recent years its use has been increasingly encouraged as part of a strategy designed to reduce Propionibacterium acnes (P acnes) resistance to antibiotics. Historically, a major drawback to BPO treatment has been irritation, which may be concentration-dependent or vehicle-dependent. A new BPO microsphere cream formulation has recently been introduced and appears to offer favorable efficacy with a very low potential for irritation. This article presents a series of patients from 2 private dermatologic practices treated with a new BPO microsphere cream formulation both as monotherapy and in combination with other acne drugs.     

Optimizing topical combination therapy for the treatment of acne vulgaris

Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.     

Adapalene: a review of its use in the treatment of acne vulgaris

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.     

Facial tolerability of topical retinoid therapy

The facial tolerability of various topical retinoids was evaluated in 253 healthy volunteers in a series of split-face, randomized, investigator-masked studies-all conducted at the same site by the same investigator. Four variables were evaluated to determine if they influenced tolerability-retinoid concentration, formulation vehicle, skin sensitivity, and individual retinoid. Lower retinoid concentrations were associated with less irritation. Vehicle influenced tolerability but whether a gel or cream formulation was better tolerated varied from retinoid to retinoid. Tolerability was superior on normal skin than "sensitive skin." On normal skin, tazarotene cream was better tolerated than tretinoin cream whereas adapalene and tretinoin microsponge gels were better tolerated than tazarotene gel. On sensitive skin, tazarotene and adapalene creams were better tolerated than tretinoin cream whereas adapalene gel was better tolerated than tazarotene gel. Retinoid concentration, vehicle, skin sensitivity, and retinoid can all affect facial tolerability. Skin vulnerability may be the most important factor.     

Solubilized benzoyl peroxide versus benzoyl peroxide/clindamycin in the treatment of moderate acne

BACKGROUND: Benzoyl peroxide (BPO) is poorly soluble. A solubilized formulation of BPO has been developed to maximize its bioavailability and enhance follicular penetration. METHODS: Patients with acne vulgaris were randomly assigned to receive solubilized BPO 5% gel on one side of the face and a BPO 5%/clindamycin 1% combination product on the contralateral side, twice daily for 4 weeks. RESULTS: Of 23 patients enrolled, 100% completed the study. Reductions in lesion count with the solubilized BPO gel were at least as great as with BPO/clindamycin--and significantly greater (P< or =.05) for noninflammatory lesions at week 1 and inflammatory lesions at week 4. Both regimens were generally well tolerated and patient satisfaction was comparable. CONCLUSIONS: Solubilized BPO 5% gel monotherapy offers significantly greater efficacy, and comparable patient satisfaction, compared with BPO/clindamycin. The early reduction in lesion counts observed with the solubilized BPO gel in the absence of an antibiotic is clinically relevant.     

Efficacy and tolerability of combined topical treatment of acne vulgaris with tretinoin and erythromycin in general practice

Efficacy and tolerability of a gel preparation with 0.025% tretinoin and 4% erythromycin in acne vulgaris was evaluated in an open multicentre study. A total of 1337 patients of either sex, aged 8 to 68 years, were enrolled in the study; 13 had to be excluded from analysis. Some 499 patients had received former acne treatment; this was described as non-efficient or poorly efficient in 90% of the patients. The treatment period lasted up to 14 weeks. Efficacy was determined by counting the acne lesions (comedones, papules and pustules) before drug administration and every second week during the treatment period. Lesions had diminished after 2 weeks in about 35% of the patients. At the end of the treatment period, comedones were eliminated in 47.0% and improved in another 41.4%. Papules were eliminated and improved in 58.2% and 32.6%, pustules in 74.3% and 18.3% respectively. Side-effects (erythema, burning, pruritus, scaling and dryness of the skin) occurred in 203 patients (15.3%). Treatment was stopped in 25 subjects (1.9%) due to intolerance reactions. The results of the present study thus confirm the high efficacy and tolerability of the fixed combination observed previously in more selected patients. The fixed combination of tretinoin and erythromycin makes retinoic acid treatment possible even by a general practitioner.     

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.     

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.     

Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris

Background: Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to antibiotics in the treatment of acne vulgaris. Objective: This review describes and evaluates recent clinical literature regarding the efficacy and tolerability of BPO. Methods: A PubMed literature search was conducted using the keywords benzoyl peroxide, acne, and combination therapy. Results: BPO is equally effective at concentrations of 2.5, 5.0 and 10%. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.     

Importance of vehicles in acne therapy

Topiucal drug therapy is an intuitively sound approach to the management of skin diseases. Depositing medication at the site of disease involvement is potentially effective and reduces systemic exposure. Topical drugs are absorbed usually by passive diffusion. In clinical practice, the choice of an optimized formulation that will be effective and well tolerated is essential. Data confirm that patient adherence with therapy leads to better outcomes and lower long-term treatment costs, while poor adherence is directly linked to poor treatment outcomes and and patient dissatisfaction. Local cutaneous irritation, which may be linked to components of the formulation and/or to the active drug itself, is a common cause of non-adherence. Well-designed drugs are important in the management of acne vulgaris and acne rosacea. Formulators have sought to improve treatment efficacy and tolerability by several different techniques, such as delayed release of the active drug, fixed combinations of two different molecules, or incorporating ingredients into the formulation vehicle that improve epidermal barrier function and offset the irritating effects of the active drugs.     

Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris

Few long-term treatment regimens for severe acne vulgaris have been investigated in clinical trials. Data were combined from two consecutive, randomized, double-blind, controlled studies to evaluate the efficacy, safety and subject satisfaction of four nine-month regimens in severe acne vulgaris treatment. Subjects were first randomized to receive doxycycline (DCN) and adapalene 0.1% - benzoyl peroxide 2.5% (A/BPO) or vehicle once daily for 12 weeks. Subjects who had at least 50% global improvement were subsequently randomized to receive A/BPO or its vehicle once daily for 24 weeks. Over nine months, there were four regimens: A/BPO and DCN followed by A/BPO, vehicle and DCN followed by A/BPO, A/BPO and DCN followed by vehicle, and vehicle and DCN followed by vehicle. Among the four regimens, A/BPO and DCN followed by A/BPO led to the highest percentage of subjects rated "clear" or "almost clear" (50.0% vs. 40.4%, 26.2% and 25.0%, respectively), biggest reduction in total lesion counts (76% vs. 70%, 51% and 47%, respectively) and greatest subject satisfaction (85.0% vs. 75.5%, 63.3% and 52.4%, respectively) at week 36. It provided a faster onset of action compared to groups started with vehicle and DCN (P<.05 at week 2). Subjects receiving A/BPO and DCN followed by vehicle experienced deterioration once the active treatment was discontinued. All regimens were safe and well-tolerated. In conclusion, efficacious initial therapy and long-term treatment are both important. An initial combination therapy with adapalene-BPO and DCN followed by longer-term adapalene-BPO treatment is an efficacious and satisfactory new regimen for severe acne subjects.     

阿达帕林凝胶治疗寻常痤疮临床观察

目的 :观察 0 1%阿达帕林凝胶治疗寻常痤疮的临床疗效和安全性。方法 :16 0例寻常痤疮患者 ,分别给予外涂 0 1%阿达帕林凝胶 (80例 )及 0 0 2 5 %全反维A酸凝胶 (80例 )。根据治疗前后炎性损害和非炎性损害总数减少的百分率评价疗效。结果 :两组痊愈率、显效率、有效率均无统计学差异 ,阿达帕林组不良反应率明显低于全反维A酸组。结论 :0 1%阿达帕林是一种局部治疗寻常痤疮的有效的安全的药物     

红蓝光联合复方维A酸红霉素凝胶治疗痤疮疗效观察

目的：探讨红蓝光联合复方维A酸红霉素凝胶治疗痤疮的疗效。方法将228例患者随机分为治疗组（114例）和对照组（114例）。对照组：每晚外用复方维A酸红霉素凝胶。治疗组：红蓝光交替照射联合复方维A酸红霉素凝胶治疗。两组均治疗8周,在治疗后8、12周对两组患者进行疗效判定及比较。结果治疗组有效率为80.70%,对照组为56.14%,两组比较差异有统计学意义（P〈0.05）。结论红蓝光交替照射联合复方维A酸凝胶治疗痤疮疗效安全肯定。     

两种用药方案治疗寻常痤疮的成本-效果分析

目的：比较复方奥硝唑搽剂和维胺酯胶囊联合维A酸霜两种用药方案治疗寻常痤疮的疗效和经济学效果。方法：以76例寻常痤疮患者为对象,随机分为两组。甲组患者应用复方奥硝唑搽剂、乙组患者给予口服维胺酯胶囊和外用0.025%维A酸霜,在治疗1个疗程后,观察两组疗效,并运用经济学原理进行分析。结果：甲、乙两组有效率分别为86.84%,89.47%,效果无显著性差异（P〉0.05）;治疗成本分别为126.40元和257.52元,有显著性差异,两组的C/E分别为1.46和2.88。结论：两种用药方案治疗寻常痤疮的有效率无显著差异,但复方奥硝唑搽剂的经济效果优于维胺酯胶囊联合维A酸霜。     

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.     

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.     

Adverse events related to topical drug treatments for acne vulgaris

ABSTRACT

Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.

Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.

Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).