Duac

Pharmacotherapeutic group: Clindamycin, combinations. ATC code: D10AF51 Clindamycin is a lincosamide antibiotic with antibacterial activity against Gram-positive aerobes and a broad spectrum of anaerobic bacteria. Lincosamides, of which clindamycin is a member, bind to the 23S subunit of the bacterial ribosome and suppress the early stages of protein synthesis. Clindamycin is primarily bacteriostatic, although at higher concentrations it may act as a latent bactericidal agent against susceptible strains. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts the compound to clindamycin, which is antibacterially active. Clinical trials in patients with acne have shown that this activity of clindamycin within acne comedones is sufficient to be effective against most strains of Propionibacterium acnes. In vitro testing demonstrated that clindamycin inhibited the growth of all tested Propionibacterium acnes cultures (MIC 0.4 mcg/ml). The amount of free fatty acids on the skin surface decreased from an initial level of approximately 14% to 2% following clindamycin application. Benzoyl peroxide exhibits a mild keratolytic effect on comedones at all stages of their development. It is an oxidising agent with bactericidal activity against Propionibacterium acnes, the microorganism implicated in the development of acne vulgaris. Benzoyl peroxide also has a sebostatic effect, counteracting the excessive sebum production associated with acne. Duac combines mild keratolytic and antibacterial properties that enable it to act effectively, particularly against the inflammatory skin lesions seen in mild to moderate acne vulgaris. The prevalence of acquired resistance may vary geographically and over time for selected organisms, and local resistance information is desirable, particularly when treating severe infections. The presence of benzoyl peroxide reduces the likelihood of developing clindamycin-resistant organisms. Combining both active substances in a single product is advantageous and supports improved patient adherence to therapy. Clinical efficacy and safety Of 1,318 patients with facial acne vulgaris involving both inflammatory and non-inflammatory lesions enrolled in five randomised, double-blind clinical trials, 396 received Duac, 396 received benzoyl peroxide, 349 received clindamycin, and 177 received vehicle. Treatment was applied once daily for 11 weeks, and patients were assessed with lesion counts performed at 2, 5, 8, and 11 weeks after treatment initiation. The mean percentage reduction in lesion count after 11 weeks of treatment is shown in the table below. Mean percentage reduction in lesion count from baseline at 11 weeks Study 150 (n = 120) Study 151 (n = 273) Study 152 (n = 280) Study 156 (n = 287) Study 158* (n = 358) Inflammatory lesions Duac 65 56 42 57 52 Benzoyl peroxide 36 37 32 57 41 Clindamycin 34 30 38 49 33 Vehicle 19 -0.4 29 - 29 Non-inflammatory lesions Duac 27 37 24 39 25 Benzoyl peroxide 12 30 16 29 23 Clindamycin -4 13 11 18 17 Vehicle -9 -5 17 - -7 Total lesions (inflammatory and non-inflammatory) Duac 41 45 31 50 41 Benzoyl peroxide 20 35 23 43 34 Clindamycin 11 22 22 33 26 Vehicle 1 -1 22 - 16 * Pivotal study Statistically significant differences are shown in bold. In all five studies, Duac produced a significant reduction in the total lesion count compared with clindamycin or vehicle. Duac demonstrated a greater effect than benzoyl peroxide, although the observed difference did not reach statistical significance in the individual studies. For inflammatory lesions, Duac was significantly more effective than clindamycin alone in four of the five studies and than benzoyl peroxide alone in three of the five studies. For non-inflammatory lesions, Duac was significantly more effective than clindamycin in four of the five studies, with a trend toward greater efficacy compared with benzoyl peroxide alone. Investigator assessment of overall improvement concluded that Duac was significantly more effective than either benzoyl peroxide alone or clindamycin alone in three of the five studies. An effect on inflammatory lesions was evident from week 2 of treatment. The effect on non-inflammatory lesions was more variable, with efficacy generally apparent after 2–5 weeks of treatment.