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

to add , in adults and adolescents aged 12 years and above (see sections 4.4 and 5.1).

The following statement was added:

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

The wording was amended from:

For application to the skin. For external use only.

to:

For cutaneous use only.

The following section on Posology was updated from:

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.

Hands should be washed after application

To:

 Adults and Adolescents (aged 12 years and above)

Duac Once Daily Gel should be applied once daily in the evening, to the entire affected area.

Patients should be advised that excessive application will not improve efficacy, but may increase the risk of skin irritation. If excessive dryness or peeling occurs, frequency of application should be reduced or application temporarily interrupted (see section 4.4).

An effect on inflammatory and non-inflammatory lesions may be seen as early as week 2-5 of treatment (see section 5.1).

The safety and efficacy of Duac Once Daily Gel has not been studied beyond 12 weeks in acne vulgaris clinical trials. Treatment with Duac Once Daily Gel should not exceed more than 12 weeks of continuous use.

Paediatric population

The safety and efficacy of Duac Once Daily Gel has not been established in children under 12 years of age, therefore Duac Once Daily Gel is not recommended for use in this population.

Elderly patients

No specific recommendations.

Method of administration

Duac Once Daily Gel should be applied in a thin film after washing gently with a mild cleanser and fully drying. If the gel does not rub into the skin easily, too much is being applied.

Hands should be washed after application.

4.4       Special warnings and precautions for use

The following paragraph was updated to read:

Contact with the mouth, eyes, lips, other mucous membranes or areas of irritated or broken skin should be avoided. Application to sensitive areas of skin should be made with caution. In case of accidental contact, rinse well with water.

The following was deleted:

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.

The following was added:

Duac Once Daily Gel should be used with caution in atopic patients, in whom further skin drying may occur.

During the first weeks of treatment, an increase in peeling and reddening will occur in most patients. Depending upon the severity of these side effects, patients can use a non-comedogenic moisturiser, temporarily reduce the frequency of application of Duac Once Daily Gel or temporarily discontinue use however; efficacy has not been established for less than once daily dosing frequencies.

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy may occur, which sometimes may be severe, especially with the use of peeling, desquamating, or abrasive agents.

If severe local irritancy (e.g. severe erythema, severe dryness and itching, severe stinging/burning) occurs, Duac Once Daily Gel should be discontinued.

As benzoyl peroxide may cause increased sensitivity to sunlight, sunlamps should not be used and deliberate or prolonged exposure to sun should be avoided or minimised. When exposure to strong sunlight cannot be avoided, patients should be advised to use a sunscreen product and wear protective clothing.

If a patient has sunburn, this should be resolved before using Duac Once Daily Gel.

The following was deleted:

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.

The following was added:

Resistance to clindamycin

Patients with a recent history of systemic or topical clindamycin or erythromycin use are more likely to have pre-existing anti-microbial resistant Propionibacterium acnes and commensal flora (see section 5.1).

Cross-resistance

The following was deleted:

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

4.5       Interaction with other medicinal products and other forms of interaction

The following was added:

No formal drug-drug interaction studies have been performed with Duac Once Daily Gel.

Duac Once Daily Gel should not be used in combination with erythromycin-containing products due to possible antagonism to the clindamycin component.

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore caution should be exercised with concomitant use.

The following was updated from:

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

 to:

Concomitant application of Duac Once Daily Gel with tretinoin, isotretinoin and tazarotene should be avoided

The following was updated from:

Potential synergism exists between clindamycin and gentamycin.

to:

since benzoyl peroxide may reduce their efficacy and increase irritation. If combination treatment is required, the products should be applied at different times of the day (e.g. one in the morning and the other in the evening).

Using topical benzoyl peroxide-containing preparations at the same time as topical sulphonamide-containing products may cause skin and facial hair to temporarily change colour (yellow/orange).

4.6       Fertility, pregnancy and lactation

The following sentence was added to the paragraph on Pregnancy:

There are limited data on the use of clindamycin and benzoyl peroxide alone in pregnant women.

The following section on Breastfeeding was updated from:

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.

To:

Use of Duac Once Daily Gel has not been studied during breastfeeding.

Percutaneous absorption of clindamycin and benzoyl peroxide is low however; it is not known whether clindamycin or benzoyl peroxide is excreted in human milk following the use of Duac Once Daily Gel. Oral and parenteral administration of clindamycin has been reported to result in the appearance of clindamycin in breast milk. For this reason, Duac Once Daily Gel should be used during lactation only if the expected benefit justifies the potential risk to the infant.

To avoid accidental ingestion by the infant if used during lactation, Duac Once Daily Gel should not be applied to the breast area.

The following section on Fertility was added:

Fertility

There are no data on the effect of Duac Once Daily Gel on fertility in humans.

4.8       Undesirable effects

The following section was updated from:

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.

To:

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).

^*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

4.9       Overdose

This section was amended to :

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.

5.1       Pharmacodynamic properties

Additional paragraph added:

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.