Newer Approaches in Topical Combination Therapy for Acne

Lisa W. Fu, BHSc; Ronald B. Vender, MD, FRCPC

Disclosures

Skin Therapy Letter. 2011;16(9) 

In This Article

Newer Fixed-dose Dual-agent Therapies

Clindamycin Phosphate 1.2% + Tretinoin 0.025% Gel (Ziana®, Biacna™)

This fixed-dose combination gel was approved by the US FDA in November 2006 and sanctioned by Health Canada in December 2010 for the once-daily treatment of acne vulgaris in patients ≥12 years of age.[8] It combines the anti-inflammatory and antibacterial actions of clindamycin with the comedolytic and anticomedogenic actions of tretinoin[5] to target several mechanisms in the pathogenesis of acne. Multiple studies have demonstrated significantly greater reductions in comedones and inflammatory lesions by 12 weeks compared with either agent alone or vehicle (Table 1).

Recommended application is once-daily at bedtime (preferred) or morning (as the vehicle delivery formulation provides for the photostability of tretinoin).[8] Patients should be instructed to use only a pea-sized amount. The vehicle is an alcohol free aqueous gel containing a unique formulation of solubilized clindamycin phosphate and stable combinations of both solubilized and crystalline tretinoin.[14] The crystalline suspension allows for tretinoin to be released in a rate-controlled manner, thereby resulting in slower and progressive follicular penetration and increased tolerability.[14] The long-term efficacy and favorable safety profile was shown in a 52-week study, with the vast majority of participants not experiencing certain local cutaneous reactions, such as no itching (92%), no burning (91%), and no stinging (94%).[15] The most frequent adverse events were acne (29/442; 7%, usually a flare), sunburn (12/442; 3%), hypersensitivity (7/442; 2%), contact dermatitis (5/442; 1%), and application-site desquamation (3/442; 1%).[15] Common class-wide side-effects from topical retinoids can include peeling, redness, dryness, itching, and photosensitivity. Tretinoin increases the skin's sensitivity to UV light, therefore patients should be reminded to avoid excessive or unnecessary sun exposure and wear sunscreen and protective clothing daily. The contraindications include Crohn's, ulcerative colitis, colitis with previous antibiotic use, and use of concomitant erythromycin containing products; it has a US FDA pregnancy category C classification.[8]

Adapalene (0.1%) + Benzoyl Peroxide (2.5%) Gel (Epiduo®, Tactuo™)

This combination gel was approved by the US FDA in January 2009 and approved by Health Canada in May 2011. It is the first fixed-dose retinoid-BPO treatment that has been developed as a convenient once-daily formulation. Adapalene has comedolytic, anticomedogenic, and anti-inflammatory properties and BPO is a highly lipophilic oxidizing agent with bactericidal and keratolytic effects.[16] BPO lowers the incidence of bacterial resistance compared with other topical antibiotics and can be used for the long-term management of acne. The complementary modes of action address three pathophysiologic processes of acne: abnormal keratinization leading to follicular plugging (comedo formation), proliferation of the bacterium P. acnes within the follicle, and inflammation. Multiple studies have demonstrated significantly greater reductions in comedones and inflammatory lesion by 12 weeks compared with either agent alone or vehicle (Table 2).

Studies have shown that this adapalene + BPO combination has a comparable safety profile to adapalene monotherapy.[18] The long-term tolerability and safety of adapalene 0.1% + BPO 2.5% gel was evaluated in 452 acne subjects over 12 months, with 327 patients completing the study (72%).[21] No subjects discontinued due to lack of efficacy, while 2% discontinued due to adverse events. Overall, treatment was well tolerated with mean scores for local intolerance (comprising erythema, dryness, scaling, and burning/stinging) reported as mild or less in all study visits. The most common adverse event was dry skin (17%). The highest irritation scores were recorded in the first week and subsequently declined thereafter. Adapalene is stable when combined with BPO in the presence or absence of light.[15] It has been assigned a pregnancy category C rating.

Patient Adherence

Acne is a chronic disease and poor medication adherence is a major contributor to treatment unresponsiveness.[10] Convenience and decreased complexity of treatment encourage patient adherence. Effective yet well tolerated treatment regimens offering simplified dosing suited to a patient's lifestyle are more likely to optimize adherence and outcomes. Patients most commonly attribute frustration with the therapeutic regimen and forgetfulness as reasons for failure to use prescribed medication.[22]

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