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 exerts antibacterial activity. Clinical trials in patients with acne have demonstrated 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). Free fatty acids on the skin surface decreased from approximately 14% to 2% following clindamycin application.
Benzoyl peroxide exhibits mild keratolytic activity against comedones at all stages of their development. It is an oxidising agent with bactericidal activity against Propionibacterium acnes, the organism implicated in the pathogenesis of acne vulgaris. Benzoyl peroxide also has a sebostatic effect, counteracting the excess sebum production associated with acne.
Duac combines mild keratolytic and antibacterial properties that enable it to act effectively, particularly against the inflamed skin lesions characteristic of 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, particularly when treating severe infections.
The presence of benzoyl peroxide reduces the likelihood of clindamycin-resistant organisms emerging.
Combining both active substances in a single product is advantageous and promotes better patient adherence to treatment.
Clinical efficacy and safety
Of 1318 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, and patients were assessed with 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
Across all five studies, Duac produced a significant reduction in the 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 five studies and than benzoyl peroxide alone in three of five studies. For non-inflammatory lesions, Duac was significantly more effective than clindamycin in four of five studies, with a trend toward better 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 five studies.
Activity against 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 skin should be performed with appropriate caution. In the event of accidental contact, rinse the affected areas 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 administered with caution to atopic patients, in whom further drying of the skin may occur.
During the first weeks of treatment, most patients may experience increased skin peeling and redness. Depending on the severity of these effects, 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.
Other concomitant topical acne treatments should be used with caution, as cumulative irritation of greater severity may occur, particularly with the concurrent use of peeling, desquamating or abrasive agents.
If marked local irritation develops (e.g. severe erythema, marked skin dryness and pruritus, marked stinging/burning), Duac should be discontinued.
Because benzoyl peroxide may cause increased sensitivity to sunlight, patients should avoid tanning beds and deliberate or prolonged exposure to sunlight, which should be avoided or, where this is not possible, kept to a minimum. If exposure to strong sunlight cannot be avoided, patients should be advised to use sunscreens for protection against UV radiation and to wear protective clothing.
If a patient is sunburned, the skin should be allowed to recover before initiating treatment with Duac.
If a patient experiences prolonged or severe diarrhoea or abdominal cramps, Duac should be discontinued immediately, as these symptoms may indicate antibiotic-associated colitis. In such cases, the patient should be evaluated using appropriate diagnostic methods to detect 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. Avoid contact with hair, textiles, furniture or floor coverings.
Resistance to clindamycin
In patients who have recently used clindamycin or erythromycin, whether systemically or topically, there is an increased likelihood of pre-existing antimicrobial resistance in Propionibacterium acnes and the commensal flora (see section 5.1).
Cross-resistance
The use of antibiotic monotherapy may give rise to cross-resistance to other antibiotics such as lincomycin and erythromycin (see section 4.5).
