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.     

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.     

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.     

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.     

Clindamycin/tretinoin: clindamycin phosphate/tretinoin gel

Connetics Corporation (USA) has licensed a first-in-class, dual-action 1% clindamycin/0.025% tretinoin aqueous gel [Clindamycin phosphate/tretinoin gel, Velac, Velac Gel] from Yamanouchi Europe BV. The product combines the anti-inflammatory and antibacterial properties of clindamycin with the beneficial effects of tretinoin [all-trans-retinoic acid], and is in phase III trials for the treatment of acne. On 1 April 2005, Yamanouchi merged with Fujisawa to form Astellas Pharma. Connetics has exclusive development and commercialisation rights for clindamycin/tretinoin gel in the US and Canada, and has non-exclusive rights to the product in Mexico. Under the licensing agreement terms, Connetics initially paid Yamanouchi a dollar US 2 million licensing fee, as well as milestone payments and royalties on future products. In the fourth quarter of 2002, a dollar US 2 million milestone payment was made to Yamanouchi following the initiation of pivotal phase III trials in the US and Canada, and in the third quarter of 2004 a dollar US 3 million milestone payment was made to Yamanouchi following the filing of an NDA to the US FDA. In March 2004, Connectics reported that clindamycin/tretinoin is approved in Europe. It appears that this approval was specifically for France. In October 2004, Connetics announced that the US FDA has accepted its NDA filing for clindamycin/tretinoin. Two pivotal phase III trials of clindamycin/tretinoin have been conducted in the US and Canada. These trials included 2219 patients with acne who received 12 weeks' treatment in the double-blind, placebo- and active-controlled trials. Results of these trials were reported in March 2004. Connetics anticipates launch of the product during mid-2005. An action date of 25 June 2005 has been given by the FDA for it to respond to the NDA submission. Phase III trials in patients with acne in Europe have shown clindamycin/tretinoin gel to be as effective and safe as other leading topical therapies. Data from a combined analysis of six controlled efficacy and safety trials of clindamycin/tretinoin have been reported. The patent for clindamycin/tretinoin gel is held by Yamanouchi in the US and internationally. Other analysts, at CIBC World Markets, were quoted saying that Evoclin represents Connetics' 'first foray' into the acne market (followed by others, such as Velac), a market that has been valued at dollar US 1.7 billion, of which that for topical antibiotics is worth approximately dollar US 500 million.     

Comparison of tretinoin solution and benzoyl peroxide lotion in the treatment of acne vulgaris

Summary

In a single-blind trial, 44 patients were treated with tretinoin solution and 44 patients were treated with benzoyl peroxide lotion for acne vulgaris for not less than 12 weeks. Both treatments were shown to have a beneficial effect. The improvements, as judged by patients' and clinical assessment and lesion count, were more marked in patients receiving tretinoin solution. Few side-effects were reported with either treatment.     

Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris

Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.     

Efficacy and safety of topical nadifloxacin and benzoyl peroxide versus clindamycin and benzoyl peroxide in acne vulgaris: A randomized controlled trial

Background:

Topical therapy with comedolytics and antibiotics are often advocated for mild and moderate severity acne vulgaris. Nadifloxacin, a new fluoroquinolone with anti-Propionibacterium acnes activity and additional anti-inflammatory activity, is approved for use in acne. This randomized controlled assessor blind trial compared the clinical effectiveness and safety of eight weeks therapy of nadifloxacin 1% versus clindamycin 1% as add-on therapy to benzoyl peroxide (2.5%) in mild to moderate grade acne.

Materials and Methods:

The efficacy parameters were changes in the total, inflammatory and non-inflammatory lesion counts, Investigator Global Assessment (IGA), and Cardiff Acne Disability Index (CADI) scales from baseline to study end (eight weeks). All treatment emergent dermatological adverse events were evaluated for safety assessment.

Results:

Out of 84 randomized subjects (43-nadifloxacin arm) and (41-clindamycin) 42 in nadifloxacin group, 37 in clindamycin group completed the study. Reduction from baseline of total, inflammatory and non-inflammatory lesion counts were highly significant in both the groups (P<0.0001), but between group differences were not significant. Significant improvement in CADI and IGA scales were noted in both groups. Between-group comparison showed no significant differences. The safety and tolerability profile of both regimens were good and statistically comparable.

Conclusions:

Topical nadifloxacin, a new fluoroquinolone is effective, tolerable, and safe for mild o moderate facial acne. Its clinical effectiveness is comparable to clindamycin when used as add-on therapy to benzoyl peroxide.KEY WORDS: Acne vulgaris, clindamycin, nadifloxacin, randomized controlled trial     

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   

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.     

The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid

A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.     

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.     

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.     

A multicenter efficacy and tolerability evaluation of benzoyl peroxide in a 10% urea vehicle for the treatment of acne vulgaris

BACKGROUND: Acne vulgaris is a common skin disease that affects 70 to 96% of individuals. Topical benzoyl peroxide has been used successfully for acne treatment; however, it may be accompanied by drying and or flaking skin. The addition of a 10% urea to the product excipient is theorized to moisturize the skin due to its humectant properties, aid in the efficacy of benzoyl peroxide due to its keratolytic properties, and effectively combat Propionibacterium acnes due to its antibacterial properties. OBJECTIVE: To assess the efficacy and tolerability of the treatment of acne vulgaris with multiple strengths of benzoyl peroxide in a 10% urea vehicle gel or cream and cleanser. Methods: A multicenter, non-randomized, open-label study in which 1,089 patients with acne vulgaris were enrolled at 133 participating physician office sites. Qualifying and consenting patients were prescribed either 4.5% or 8.5% benzoyl peroxide in a 10% urea vehicle cream or gel and cleanser. Additional medications were permitted during the study with the exception of those containing benzoyl peroxide. The physician assessed lesion counts, both inflammatory and non-inflammatory, at baseline and Week 4. Dryness and erythema were rated by the physician on a scale from 0 (none) to 8 (severe or deep) at baseline and Week 4. RESULTS: Nine hundred sixty-three patients completed the study. The following significant treatment arms were analyzed: patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle product only, patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products along with oral doxycycline, and patients treated with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products along with oral minocycline. A 44% (n=567) mean reduction in total lesion count was observed after 4 weeks of treatment with 4.5%/8.5% benzoyl peroxide in a 10% urea vehicle products only. Dual therapy using oral doxycycline (n=17) proved to be even more effective with a significant mean reduction in lesion count of 52% after only 4 weeks of treatment. Dual therapy using oral minocycline (n=21) yielded a significant mean reduction in lesion count of 34% after 14 weeks of treatment. The overall tolerability of the treatment illustrated the utility of urea as a moisturizing agent. CONCLUSION: Benzoyl peroxide in a 10% urea vehicle gel or cream and cleanser, used once daily for 4 weeks was found to be both effective and well tolerated for the treatment of symptoms related to acne vulgaris.     

Benzoyl peroxide in the treatment of acne vulgaris: a double-blind, multi-centre comparative study of 'Quinoderm' cream and 'Quinoderm' cream with hydrocortisone versus their base vehicle alone and a benzoyl peroxide only gel preparation

A double-blind, multi-centre general practice study was carried out to compare the effectiveness of benzoyl peroxide/potassium hydroxyquinoline sulphate cream, with or without hydrocortisone, its aqueous astringent cream base alone, and a benzoyl peroxide alcoholic gel in the treatment of 107 patients with acne vulgaris. Patients on entry were allocated at random to one of four treatment groups and instructed to apply the medication twice daily to all affected areas for 12 weeks. Assessments of the severity of acne on the face, chest and back, and response to treatment were made at 2, 4, 8 and 12 weeks. Acceptability of the treatment, i.e. 'greasiness', was also assessed by patients. The results showed that the combination cream preparation produced a greater reduction in acne scores than did the base or benzoyl peroxide alone. The addition of 1% hydrocortisone eliminated the flare reaction to benzoyl peroxide seen in patients in the other two active treatment groups. The majority of patients found the preparations cosmetically acceptable.     

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.     

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.     

异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮

目的观察异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮的疗效。方法将201例Ⅱ～Ⅳ度寻常痤疮患者随机分为2组,治疗组106例,对照组95例。治疗组予异维A酸红霉素凝胶联合过氧苯甲酰凝胶,对照组给予异维A酸红霉素凝胶治疗。每2周随访1次,观察疗效及不良反应,8周后进行治疗评定。结果治疗组痊愈率和有效率(58.49%、96.23%)高于对照组(36.84%、88.42%)。结论异维A酸红霉素凝胶联合过氧苯甲酰凝胶治疗中、重度痤疮较单纯外用异维A酸红霉素凝胶疗效好。     

Topical antibacterial therapy for acne vulgaris

Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial treatments indicated for mild-to-moderate acne vulgaris. Topical antibiotics act both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous follicle and as anti-inflammatory agents. Benzoyl peroxide is a powerful antimicrobial agent that rapidly destroys both bacterial organisms and yeasts. Topical clindamycin and erythromycin have been proven to be effective against inflammatory acne vulgaris in concentrations of 1-4% with or without the addition of zinc. However, none of the antibacterials tested was more effective than benzoyl peroxide, which also has the advantage of not being associated with antimicrobial resistance.Topical antibacterial therapy should be discontinued once improvement is observed. If no improvement is observed within 6-8 weeks, the agent should be discontinued and a therapeutic switch considered. The primary limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous irritation or dryness.Antibacterial therapy can be used in combination with other agents. Combining topical antibiotics and topical retinoids may enhance the efficacy, since the retinoid will improve the penetration of the antibiotic. Combining a topical antibiotic with benzoyl peroxide may increase the bactericidal effect of the antibiotic and reduce the potential for bacterial resistance. Topical and oral antibacterials should not be used in combination for the treatment of acne vulgaris, since this association may increase the risk of bacterial resistance.