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.
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 due 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 administered with caution in atopic patients, in whom further skin drying may occur.
During the first weeks of treatment, increased skin peeling and erythema may occur in most patients. Depending on the severity of these adverse 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 applied less frequently than once daily has not been established.
Concomitant topical acne therapy should be used with caution, as cumulative irritation of a more serious nature may occur, particularly with concurrent use of peeling, desquamating, or abrasive agents.
If marked local irritation occurs (e.g. severe erythema, marked skin dryness and pruritus, severe stinging/burning), Duac should be discontinued.
As benzoyl peroxide may increase sensitivity to sunlight, patients should avoid the use of sunlamps and deliberate or prolonged exposure to sunlight, or at least minimise sun exposure. Where strong sun exposure cannot be avoided, patients should be advised to use sunscreens and wear protective clothing.
If a patient is sunburned, the skin should be allowed to recover before Duac is started.
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 investigated using appropriate diagnostic methods to determine the presence of Clostridium difficile and its toxin, including colonoscopy, and alternative treatment options should be considered for the suspected colitis.
The product may bleach hair or coloured fabrics. Avoid contact with hair, fabrics, furniture, and floor coverings.
Resistance to clindamycin
In patients who have recently used clindamycin or erythromycin, whether systemically or topically, there is a greater likelihood of pre-existing antimicrobial resistance in Propionibacterium acnes and commensal flora (see section 5.1).
Cross-resistance
Antibiotic monotherapy may give rise to cross-resistance to other antibiotics, such as lincomycin and erythromycin (see section 4.5).
