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 inhibit the early stages of protein synthesis. Clindamycin is primarily bacteriostatic, although at higher concentrations it may act as a slow bactericidal agent against susceptible strains.
Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts the compound to clindamycin, which has 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 in vitro testing, clindamycin inhibited the growth of all tested cultures of Propionibacterium acnes (MIC 0.4 mcg/mL). The level of 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 development. It is an oxidising agent with bactericidal activity against Propionibacterium acnes, the microorganism implicated in the pathogenesis 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 against the inflammatory 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 the two 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 across five randomised, double-blind clinical studies, 396 patients received Duac, 396 received benzoyl peroxide, 349 received clindamycin and 177 received vehicle. Treatment was applied once daily for 11 weeks, and patients were evaluated and lesion counts recorded 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 showed greater efficacy than benzoyl peroxide, although the observed difference did not reach statistical significance in 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 greater efficacy compared with benzoyl peroxide alone.
The overall improvement in patients' condition was assessed by the physician, who concluded that Duac was significantly more effective than benzoyl peroxide alone and than 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 evident after 2 to 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. The product should be applied with appropriate caution to sensitive areas of the skin. 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 used with caution in atopic patients, in whom further drying of the skin may occur.
During the first few weeks of treatment, most patients may experience increased peeling and reddening of the skin. Depending on the severity of these effects, patients may apply a non-comedogenic moisturiser, temporarily reduce the frequency of gel application or temporarily discontinue use; however, efficacy with application less frequent than once daily has not been established.
Other concomitant topical acne treatments should be used with caution because of the potential for cumulative irritation, which may be more severe, particularly with concurrent use of peeling, desquamating or abrasive agents.
If marked local irritation occurs (e.g. severe erythema, pronounced skin dryness and itching, intense 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 likewise be avoided or at least minimised. Where strong sunlight cannot be avoided, patients should be advised to use sunscreen and protective clothing.
If a patient has sunburn, the skin should first 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 be indicative of antibiotic-associated colitis. In such cases, the patient should be evaluated using appropriate diagnostic methods, including colonoscopy, to detect Clostridium difficile and its toxin, and alternative treatment options for the suspected colitis should be considered.
The product may bleach hair or coloured fabrics. Avoid contact with hair, textiles, furniture and floor coverings.
Resistance to clindamycin
Patients who have recently used clindamycin or erythromycin, either systemically or topically, are more likely to have pre-existing antimicrobial resistance of Propionibacterium acnes and commensal flora (see section 5.1).
Cross-resistance
With antibiotic monotherapy, cross-resistance may develop to other antibiotics such as lincomycin and erythromycin (see section 4.5).
