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, including clindamycin, bind to the 23S subunit of the bacterial ribosome and inhibit the early stages of protein synthesis. Clindamycin is predominantly bacteriostatic, although at higher concentrations it may exert a bactericidal effect on susceptible strains.
Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts the compound into clindamycin, which has antibacterial activity. Clinical trials in patients with acne have shown that this action of clindamycin within acne comedones is sufficiently effective against most strains of Propionibacterium acnes. In vitro, clindamycin inhibited the growth of all tested cultures of Propionibacterium acnes (MIC 0.4 mcg/ml). Following application of clindamycin, the level of free fatty acids on the skin surface decreased from approximately 14% to 2%.
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 organism 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. Local information on resistance is desirable, especially when treating severe infections.
The presence of benzoyl peroxide reduces the likelihood of organisms developing resistance to clindamycin.
Combining both active substances in a single product is advantageous and improves patient adherence to treatment.
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 studies, 396 received Duac, 396 received benzoyl peroxide, 349 received clindamycin and 177 received vehicle. Treatment was applied once daily for 11 weeks, with patient assessments and lesion counts performed at 2, 5, 8 and 11 weeks after the start of treatment.
The mean percentage reduction in lesion counts after 11 weeks of treatment is shown in the following table.
Mean percentage reduction in lesion counts 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 total lesion count compared with clindamycin or vehicle. Duac demonstrated greater efficacy 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 clear trend towards greater efficacy compared with benzoyl peroxide alone.
The physician's global assessment of patient improvement concluded that Duac was significantly more effective than benzoyl peroxide alone and than clindamycin alone in three of the five studies.
The effect on inflammatory lesions was evident from week 2 of treatment. The effect on non-inflammatory lesions was more variable, with efficacy typically apparent after 2–5 weeks of treatment.
Warnings
Contact of the gel with the mouth, eyes, lips, other mucous membranes, or irritated or broken skin should be avoided. Application to sensitive areas of the skin should be performed with appropriate caution. In the event of accidental contact, rinse the affected area with water.
Duac should be used with caution in patients with a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
Duac should be used with caution in atopic patients, in whom further drying of the skin may occur.
During the first weeks of treatment, most patients may experience increased peeling and reddening of the skin. Depending on the severity of these adverse reactions, patients may use a non-comedogenic moisturiser, temporarily reduce the frequency of gel application, or temporarily discontinue use; however, the efficacy of the product when used less often than once daily has not been established.
Concomitant topical acne therapy should be used with caution, as a cumulative irritant effect of greater severity may occur, particularly with the concurrent use of peeling, desquamating or abrasive agents.
If marked local irritation occurs (e.g. severe erythema, intense skin dryness and pruritus, severe stinging/burning), application of Duac should be discontinued.
Because benzoyl peroxide may cause increased sensitivity to sunlight, patients should avoid the use of sunbeds and intentional or prolonged exposure to sunlight, which should be avoided or at least minimised. If strong sunlight cannot be avoided, patients should be advised to use a sunscreen and to wear protective clothing.
If a patient experiences sunburn, the skin should first be allowed to recover before initiating treatment with Duac.
If prolonged or severe diarrhoea or abdominal cramps occur, treatment with Duac should be discontinued immediately, as these symptoms may be indicative of antibiotic-associated colitis. In such cases, the patient should be evaluated using appropriate diagnostic methods to detect the presence of Clostridium difficile and its toxin, including colonoscopy, and alternative treatment options should be considered in light of the suspected colitis.
The product may bleach hair or coloured fabrics. Contact with hair, textiles, furniture or floor coverings should be avoided.
Resistance to clindamycin
Patients who have recently used clindamycin or erythromycin, either systemically or topically, are more likely to harbour pre-existing antimicrobial resistance in Propionibacterium acnes and commensal flora (see section 5.1).
Cross-resistance
With antibiotic monotherapy, cross-resistance to other antibiotics, such as lincomycin and erythromycin, may develop (see section 4.5).
