EPIDUO Gel Ref.[50792] Active ingredients: Adapalene Benzoyl peroxide

Pharmacotherapeutic group: D10A Anti-Acne Preparations for Topical Use ATC code: D10AD53

Epiduo combines two active substances, which act through different, but complementary, mechanisms of action.

Adapalene: Adapalene is a chemically stable, naphthoic acid derivative with retinoid-like activity. Biochemical and pharmacological profile studies have demonstrated that adapalene acts in the pathology of Acne vulgaris: it is a potent modulator of cellular differentiation and keratinisation and it has anti-inflammatory properties. Mechanistically, adapalene binds to specific retinoic acid nuclear receptors. Current evidence suggests that topical adapalene normalizes the differentiation of follicular epithelial cells resulting in decreased microcomedone formation. Adapalene inhibits the chemotactic (directional) and chemokinetic (random) responses of human polymorphonuclear leucocytes in in vitro assay models; it also inhibits the metabolism of arachidonic acid to inflammatory mediators. In vitro studies have shown inhibition of the AP-1 factors and the inhibition of the expression of toll like receptors 2. This profile suggests that the cell mediated inflammatory component of acne is reduced by adapalene.

Benzoyl peroxide: Benzoyl peroxide has been shown to have antimicrobial activity; particularly against P. acnes, which is abnormally present in the acne-affected pilosebaceous unit. Additionally, benzoyl peroxide has demonstrated exfoliative and keratolytic activities. Benzoyl peroxide is also sebostatic, counteracting the excessive sebum production associated with acne.

Clinical efficacy of Epiduo

The safety and efficacy of Epiduo applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical studies of similar design, comparing Epiduo to its individual active components, adapalene and benzoyl peroxide, and to the gel vehicle in acne patients. A total of 2185 patients were enrolled in Study 1 and Study 2. The distribution of patients in the two studies was approximately 49% male and 51% female, 12 years of age or older (mean age: 18.3 years; range 12-50), presenting 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions at baseline. The patients treated the face and other acne affected areas as needed once daily in the evening.

The efficacy criteria were:

1. Success rate, percentage of patients rated ‘Clear’ and ‘Almost Clear’ at Week based on the Investigator’s Global Assessment (IGA);
2. Change and Percent Change from baseline at Week 12 in

• Inflammatory lesion counts
• Non-inflammatory lesion counts
• Total lesion count

The efficacy results are presented for each study in Table 1 and combined results in Table 2. Epiduo was shown to be more effective compared to its monads and gel vehicle in both studies. Overall, the net beneficial effect (active minus vehicle) obtained from Epiduo was greater than the sum of the net benefits obtained from the individual components, thus indicating a potentiation of the therapeutic activities of these substances when used in a fixed-dose combination. An early treatment effect of Epiduo was consistently observed in Study 1 and Study 2 for Inflammatory Lesions at Week 1 of treatment. Noninflammatory lesions (open and closed comedones) noticeably responded between the first and fourth week of treatment. The benefit on nodules in acne has not been established.

Table 1. Clinical efficacy in two comparative trials:

Table 2. Clinical efficacy in combined comparative trials: