Pharmacotherapeutic Group: Clindamycin, combinations. ATC Code: D10AF51.
Pharmacology: Pharmacodynamics: Clindamycin is a lincosamide antibiotic with a bacteriostatic action against Gram-positive aerobes and a wide range of anaerobic bacteria. Lincosamides such as clindamycin bind to the 23S subunit of the bacterial ribosome and inhibit the early stages of protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains.
Although clindamycin phosphate is inactive in-vitro, rapid in-vivo hydrolysis converts this compound to the antibacterial active clindamycin. Clindamycin activity has been demonstrated clinically in comedones from acne patients at sufficient levels to be active against most strains of Propionibacterium acnes. Clindamycin in-vitro inhibits all Propionibacterium acnes cultures tested (MIC 0.4mcg/ml). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin.
Benzoyl peroxide is mildly keratolytic acting against comedones at all stages of their development. It is an oxidizing agent with bactericidal activity against Propionibacterium acnes, the organism implicated in acne vulgaris. Furthermore it is sebostatic, counteracting the excessive sebum production associated with acne.
Duac Once Daily Gel has a combination of mild keratolytic and antibacterial properties providing activity particularly against inflamed lesions of mild to moderate acne vulgaris.
The prevalence of acquired resistance may vary geographically and with time for selected species. Local information of resistance is desirable, particularly when treating severe infections.
The inclusion of benzoyl peroxide reduces the potential for the emergence of organisms resistance to clindamycin.
The presentation of both active ingredients in one product is more convenient and ensures patient compliance. Clinical efficacy and safety: In five randomized double-blind clinical studies of 1318 patients with facial acne vulgaris with both inflammatory and non-inflammatory lesions, 396 used Duac, 396 used benzoyl peroxide, 349 used clindamycin and 177 used vehicle. Treatment was applied once daily for 11 weeks and patients were evaluated and lesions counted at 2, 5, 8 and 11 weeks.
The mean percentage reduction in the number of lesions after 11 weeks is shown in the table. (See Table 1.)
Click on icon to see table/diagram/image
The reduction in total lesions was significantly greater with Duac Once Daily Gel than clindamycin or vehicle in all five studies. The improvement was consistently greater with Duac Once Daily Gel than benzoyl peroxide, but the difference did not achieve statistical significance in individual studies.
Against inflammatory lesions, Duac Once Daily Gel was significantly superior to clindamycin alone in four or five studies and to benzoyl peroxide alone in three of five studies. Against non-inflammatory lesions, Duac Once Daily Gel was significantly better than clindamycin in four of five studies, and tended to be better than benzoyl peroxide alone.
Overall improvement in acne was assessed by the physician and was significantly better with Duac Once Daily Gel than with either benzoyl peroxide or clindamycin alone in three of five studies.
An effect on inflammatory lesions was apparent from week 2 of treatment. The effect on non-inflammatory lesions was more variable, with efficacy generally apparent after 2-5 weeks of treatment.
Pharmacokinetics: In a maximized percutaneous absorption study the mean plasma clindamycin levels during a four week dosing period for Duac Once Daily Gel were negligible (0.043% of applied dose).
The presence of benzoyl peroxide in the formulation did not have an effect on the percutaneous absorption of clindamycin.
Radio-label studies have shown that absorption of benzoyl peroxide through the skin can only occur following its conversion to benzoic acid. Benzoic acid is mostly conjugated to form hippuric acid, which is excreted via the kidneys.
Toxicology: Preclinical safety data: Duac Once Daily: In a two year carcinogenicity study in mice, topical administration of Duac Once Daily Gel showed no evidence of increased carcinogenic risk, compared with controls.
In a photococarcinogenicity study in mice, a slight reduction in the median time to tumour formation was observed relative to controls following concurrent exposure to Duac Once Daily Gel and simulated sunlight. The clinical relevance of the findings in this study is unknown.
Repeat-dose dermal toxicity studies conducted on Duac Once Daily Gel, in two species, for up to 90 days, revealed no toxic effects, apart from minor local irritation.
An ocular irritation study found Duac Once Daily Gel to be only very slightly irritant.
Benzoyl peroxide: In animal toxicity studies, benzoyl peroxide was well tolerated when applied topically.
Although high doses of benzoyl peroxide have been shown to induce DNA strand breaks, the available data from other mutagenicity studies, carcinogenicity studies and a photo co-carcinogenicity study indicate that benzoyl peroxide is not a carcinogen or a photocarcinogen.
No reproductive toxicity data are available.
Clindamycin: In-vitro and in-vivo studies did not reveal any mutagenic potential of clindamycin. No long-term animal studies investigating the tumorigenic potential of clindamycin have been conducted.
Otherwise, preclinical data reveal no special hazard for humans based on conventional studies of single and repeat-dose toxicity and toxicity to reproduction.