Excessive application of Duac Once Daily Gel may result in severe irritation. In this event, discontinue use and wait until the skin has recovered.
Topically applied benzoyl peroxide is not generally absorbed in sufficient amounts to produce systemic effects.
Excessive application of topically applied clindamycin may result in absorption of sufficient amounts to produce systemic effects.
In the event of accidental ingestion of Duac Once Daily Gel, gastrointestinal adverse reactions similar to those seen with systemically administered clindamycin may be seen.
Appropriate symptomatic measures should be taken to provide relief from irritation due to excessive application.
Accidental ingestion should be managed clinically or as recommended by the National Poisons Centre, where available.
Adverse drug reactions (ADRs) are summarised below for Duac Once Daily Gel as a combination including any additional ADRs that have been reported for the single topical active ingredients, benzoyl peroxide or clindamycin. Adverse drug reactions are listed by MedDRA system organ class and by frequency. Frequencies are defined as: very common (>1/10); common (>1/100 and <1/10); uncommon (>1/1,000 and <1/100); rare (>1/10,000 and <1/1,000) and not known (cannot be estimated from the available data).
| MedDRA SOC | Very Common | Common | Uncommon | Not known** |
| Immune system disorders | Allergic reactions including hypersensitivity and anaphylaxis | |||
| Nervous system disorders* | Paraesthesia | |||
| Gastrointestinal disorders | Colitis (including pseudomembranous colitis), haemorrhagic diarrhoea, diarrhoea, abdominal pain | |||
| Skin and subcutaneous tissue disorders* | Erythema, peeling, dryness (Generally reported as 'mild' in severity) | Burning sensation | Dermatitis, pruritus, erythematous rash, worsening of acne | Urticaria |
| General disorders and Administration site conditions | Application site reactions including skin discoloration |
*At site of application. **Based on post-marketing reports. Since these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency however, systemic reactions are rarely seen.
In addition to the ADRs reported in the table above, in the pivotal trial conducted with topical clindamycin 1%/benzoyl peroxide 3% gel, application site photosensitivity reaction was also reported commonly.
Also in addition to the ADRs reported above, in studies conducted with topical clindamycin alone, headache and application site pain were reported commonly.
Local Tolerability
During the five clinical trials with Duac Once Daily Gel, all patients were graded for facial erythema, peeling, burning, and dryness on the following scale: 0 = absent, 1 = mild, 2 = moderate and 3 = severe. The percentage of patients that had symptoms present before treatment (at baseline) and during treatment were as follows:
Local Tolerability Assessments for Subjects (N=397) in the Duac Once Daily Gel Group during the Phase 3 Studies
| Before Treatment (Baseline) | During Treatment | |||||
| Mild | Moderate | Severe | Mild | Moderate | Severe | |
| Erythema | 28% | 3% | 0 | 26% | 5% | 0 |
| Peeling | 6% | <1% | 0 | 17% | 2% | 0 |
| Burning | 3% | <1% | 0 | 5% | <1% | 0 |
| Dryness | 6% | <1% | 0 | 15% | 1% | 0 |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Duac Once Daily Gel
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.
Pharmacotherapeutic group: Clindamycin, combinations
ATC Code: D10AF51
Clindamycin is a lincosamide antibiotic with 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 oxidising 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 resistant to clindamycin.
The presentation of both active ingredients in one product is more convenient and ensures patient compliance.
Clinical efficacy and safety
In five randomised 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. Mean percent reduction in number of lesions from baseline after 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 Once Daily Gel | 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 Once Daily Gel | 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 plus non-inflammatory lesions) | ||||||
| Duac Once Daily Gel | 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 highlighted in bold.
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 of 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.
In a maximised 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.
Not relevant
No special requirements.
