Stiefel Ireland

Duac Once Daily 10mg/g + 50mg/g Gel

1g of gel contains:

10mg clindamycin as clindamycin phosphate

50mg anhydrous benzoyl peroxide as hydrous benzoyl peroxide

For a full list of excipients, see section 6.1.

Gel

White to slightly yellow homogeneous gel

Mild to moderate acne vulgaris, particularly inflammatory lesions.

See section 5.1

For application to the skin. For external use only.

Adults and adolescents

Duac Once Daily Gel should be applied once daily in the evening, to affected areas after the skin has been thoroughly washed, rinsed with warm water and gently patted dry.

Use in Children

The safety and efficacy of Duac Once Daily Gel has not been established in prepubescent children (under 12 years of age), since acne vulgaris rarely presents in this age group.

Use in the Elderly

No specific recommendations.

Treatment with Duac Once Daily Gel should not exceed more than 12 weeks of continuous use.

Duac Once Daily Gel must not be administered to patients with known hypersensitivity to:

-clindamycin

-lincomycin

-benzoyl peroxide

-any of the excipients in the formulation.

Contact with the mouth, eyes and mucous membranes and with abraded or eczematous skin should be avoided. Application to sensitive areas of skin should be made with caution. In the event of accidental contact with the eyes, bathe with copious amounts of water.

Duac Once Daily Gel should be used with caution in patients with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis. It should also be used with caution in atopic patients, in whom further skin drying may occur.

The frequency of application should be reduced if excessive irritation or dryness develops.

If prolonged or significant diarrhoea occurs or the patient suffers from abdominal cramps, treatment with Duac Once Daily Gel should be discontinued immediately, as the symptoms may indicate antibiotic-associated colitis. Suitable diagnostic methods, such as the determination of Clostridium difficile and toxin and, if necessary, colonoscopy should be employed and treatment options for colitis considered.

The product may bleach hair or coloured fabrics.

It is recommended that exposure to sun or sunlamps should be minimised.

Patients should be advised that, in some cases, 4-6 weeks of treatment may be required before the full therapeutic effect is observed.

Cross-resistance may occur with other antibiotics such as lincomycin and erythromycin when using antibiotic monotherapy.

Local recommendations about antibiotic use and prevalence of acquired resistance should be taken into consideration.

Concomitant topical antibiotics, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol and/or astringents, should be used with caution as a cumulative irritant effect may occur.

Simultaneous application of Duac Once Daily Gel and topical acne preparations containing vitamin A derivatives should be avoided.

Potential synergism exists between clindamycin and gentamycin.

There are no adequate data from the use of Duac Once Daily Gel in pregnant women. Animal reproductive/ developmental studies have not been conducted with Duac Once Daily Gel or benzoyl peroxide. Data from a limited number of pregnancies exposed in the first trimester to clindamycin indicate no adverse effects of clindamycin on pregnancy or on the health of the foetus/new born child. Reproduction studies in rats and mice, using subcutaneous and oral doses of clindamycin, revealed no evidence of impaired fertility or harm to the foetus due to clindamycin.

The safety of Duac Once Daily Gel in human pregnancy is not established. Therefore, Duac Once Daily Gel should only be prescribed to pregnant women after careful risk/benefit assessment by the physician in charge.

Women of child-bearing potential

There are no contraindications in women of child-bearing potential who are practising adequate contraception. However, due to the lack of clinical studies in pregnant women, Duac Once Daily Gel should be used with caution when adequate contraception is not being practised.

Use during lactation

There is no restriction on the use of benzoyl peroxide during lactation.

It is not known whether clindamycin is excreted in human milk following the use of Duac Once Daily Gel, but oral and parenteral administration of clindamycin has been reported to result in the appearance of clindamycin in breast milk. For this reason, treatment of nursing mothers with Duac Once Daily Gel is not recommended.

Not relevant

Duac Once Daily Gel may cause:

Skin and Subcutaneous Tissue Disorders; erythema, peeling, dryness, and pruritus at the site of application.

Very rarely:

Nervous System Disorders; paraesthesia,

Skin and Subcutaneous Tissue Disorders; worsening of acne and contact dermatitis can occur.

These localised effects are typically mild to moderate. Reported frequencies in clinical trials are:

Very common (>1/10)

Skin and Subcutaneous Tissue Disorders; Erythema, Peeling, Dryness

Common (>1/100, <1/10)

Skin and Subcutaneous Tissue Disorders; Burning, Pruritus

Uncommon (>1/1000, <1/100)

Nervous System Disorder; Paraesthesia

Skin and Subcutaneous Tissue Disorders; Worsening of acne

Post marketing data have shown a much lower incidence of these localised effects.

In a few susceptible individuals there have been isolated reports of pseudomembraneous colitis or diarrhoea due to other topical treatments containing clindamycin. This is unlikely to occur with Duac Once Daily Gel, as plasma levels have been determined and the percutaneous absorption of clindamycin is clinically negligible.

With long term use of Duac Once Daily Gel resistance may occur.

Immune System Disorders

In the post-marketing environment there have been isolated instances of allergic reactions which can be sudden and severe.

No case of overdose has been reported.

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.

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

* 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.

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.

Duac Once Daily Gel

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. No other preclinical studies have been performed with Duac Once Daily Gel, but only for the single substances benzoyl peroxide and clindamycin.

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.

Carbomer (50000mPa.s)

Dimeticone (100mm².s^-1)

Disodium Lauryl Sulfosuccinate

Edetate Disodium

Glycerol

Silica, Colloidal Hydrated

Poloxamer 182

Purified Water

Sodium Hydroxide

Not applicable.

Shelf life of medicinal product as packaged for sale

18 months

Shelf life of medicinal product after dispensing

2 months

Store in a refrigerator (2°C-8°C). Do not freeze.

Storage conditions after dispensing

Do not store above 25°C.

Internally lacquered membrane-sealed aluminium tubes fitted with a polyethylene screw-cap, packed into a carton.

Pack sizes: 5, 6, 15, 25, 30, 50, 55, 60 and 70 grams.

Not all pack sizes may be marketed.

No special requirements.

GlaxoSmithKline (Ireland) Ltd

Stonemasons Way

Rathfarnham

Dublin 16

Ireland

Trading as Stiefel

PA 1077/120/001

Date of first authorisation: 22 July 2005

Date of last renewal: 16 September 2008

April 2012