SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Finacea 15% Gel

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

1 g Finacea Gel contains 150 mg (15%) azelaic acid.

Excipients with known effect:

1 mg Benzoic acid /g Gel 0.12 g Propylene glycol /g Gel

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Gel

White to yellowish-white opaque gel

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the relief of mild to moderate papular-pustular acne of the facial area. For the topical treatment of papulopustular rosacea.

4.2    Posology and method of administration

Finacea 15 % Gel is intended for cutaneous use only.

Posology

Finacea Gel should be applied to the affected skin areas twice a day (in the morning and in the evening) and rubbed in gently. Approximately 0.5 g = 2.5 cm (1 inch) of gel is sufficient for the entire facial area.

Pediatric population

Use in adolescents (12-18 years of age) for the treatment of acne vulgaris. Dose adjustment is not required when Finacea Gel is administered to adolescents aged 12-18 years.

The safety and efficacy of Finacea Gel for the treatment of acne vulgaris in children below the age of 12 years have not been established.

The safety and efficacy of Finacea Gel for the treatment of papulopustular rosacea in children below the age of 18 years have not been established.

Method of administration

Before Finacea Gel is applied, the skin should be thoroughly cleaned with plain water and dried. A mild skin-cleansing agent may be used.

Occlusive dressing or wrappings should not be used, and hands should be washed after applying the gel.

In the event of skin irritation (see section 4.8 Undesirable effects), the amount of gel per application should be reduced or the frequency of use of Finacea Gel should be reduced to once a day until the irritation ceases. If required, the treatment should be temporarily interrupted for a few days.

It is important to use Finacea Gel continuously over the entire period of treatment. The duration of use of Finacea Gel can vary from person to person and also depends on the severity of the skin disorder.

Acne: In general, a distinct improvement becomes apparent after 4 weeks. To obtain optimum results, Finacea Gel can be used over several months in accordance with the clinical outcome. In case of no improvement after 1 month or exacerbation of acne, Finacea Gel should be discontinued and other therapeutic options should be considered.

Rosacea: In general, a distinct improvement becomes apparent after 4 weeks of treatment. To obtain optimum results, Finacea Gel can be used over several months in accordance with the clinical outcome. In case of no improvement after 2 month or exacerbation of rosacea, Finacea Gel should be discontinued and other therapeutic options should be considered.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

For external use only.

Finacea Gel contains benzoic acid which is mildly irritant to the skin, eyes and mucous membranes and propylene glycol which may cause skin irritation. Care should be taken to avoid contact with the eyes, mouth and other mucous membranes, and patients should be instructed accordingly (see section 5.3 Preclinical safety data). In the event of accidental contact, the eyes, mouth

and/or affected mucous membranes should be washed with large amounts of water. If eye irritation persists, patients should consult a physician. The hands should be washed after each application of Finacea Gel.

It is advisable to avoid the concomitant use of alcoholic cleansers, tinctures and astringents, abrasives and peeling agents in patients using Finacea Gel for treatment of rosacea.

Worsening of asthma in patients treated with azelaic acid has been reported rarely during post-marketing surveillance.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. The composition of Finacea Gel gives no indication of any undesired interactions of the single components that could adversely affect the safety of the product. No drug-specific interactions were noted during any of the controlled clinical trials.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate and well-controlled studies of topically administered azelaic acid in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3 Preclinical safety data).

Caution should be exercised when prescribing azelaic acid to pregnant women. Lactation

It is not known if azelaic acid is secreted into human milk in vivo. However an in vitro equilibrium dialysis experiment demonstrated that passage of drug into maternal milk may occur. But the distribution of azelaic acid into maternal milk is not expected to cause a significant change from baseline azelaic acid levels in the milk.

Azelaic acid is not concentrated in milk and less than 4% of topically applied azelaic acid is systemically absorbed, not increasing endogenous azelaic acid exposure above physiological levels. However, caution should be exercised when Finacea Gel is administered to a nursing woman.

Infants must not come into contact with treated skin/breast.

4.7 Effects on ability to drive and use machines

Finacea Gel has no influence on the ability to drive and use machines.

4.8 Undesirable effects

From clinical studies and post-marketing surveillance, the most frequently observed side effects included application site pruritus, application site burning and application site pain.

Frequencies of side-effects observed in clinical studies and post-marketing surveillance and given in the table below are defined according to the MedDRA frequency convention:

Very common (>1/10),

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

Uncommon (>1/1,000; <1/100),

Rare (>1/10,000, <1/1,000),

Very rare (<1/10,000),

Not known (cannot be estimated from the available data).

System Organ Class	Very common	Common	Uncommon	Rare
Immune system disorders				drug hypersensitivity, worsening of asthma (see section 4.4)
Skin and subcutaneous tissue disorders			contact dermatitis, acne*
General disorders and administration site conditions	application site burning, application site pain, application site pruritus	application site rash, application site paraesthesia, application site dryness, application site oedema*	application site erythema, application site exfoliation**, application site warmth**, application site discolouration**, application site discomfort*, application site urticaria*

* for indication Rosacea ** for indication Acne

Generally, local skin irritation regresses in the course of the treatment.

Pediatric population

Treatment of acne vulgaris in adolescents 12-18 years of age:

In 4 clinical phase II and II/III studies involving adolescents 12-17 years of age (120/383; 31%), the overall incidence of adverse events for Finacea Gel was similar for the groups aged 12-17 years (40%), aged >18 years (37%) and for the entire patient population (38%). This similarity also applied to the group aged 12-20 years (40%).

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.

4.9 Overdose

Due to the very low local and systemic toxicity of azelaic acid intoxication is unlikely.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other anti-acne preparations for topical use, ATC

code: D10A X03

Acne:

An antimicrobial action and a direct influence on follicular hyperkeratosis are assumed to be the basis for the therapeutic efficacy of azelaic acid in acne.

In vitro and in vivo, azelaic acid inhibits the proliferation of keratinocytes and normalizes the disturbed terminal epidermal differentiation processes in acne. Clinically, a significant reduction of the colonization density of Propionibacterium acnes and a significant reduction in the fraction of free fatty acids in the skin surface lipids are observed.

In two double blind randomized clinical studies Finacea Gel was significantly superior to its vehicle in the median reduction of the sum of papules and pustules, and was 6 % less effective than benzoyl peroxide 5 % (p=0.056).

In these studies effectiveness of Finacea Gel on comedones has been evaluated as a secondary parameter. Finacea Gel was more effective than its vehicle in the median relative reduction of comedones, and was less effective in comparison to benzoyl peroxide 5 %.

Rosacea:

The mechanism by which azelaic acid interferes with the pathogenic events in rosacea is unknown. Several in vitro and ex vivo investigations indicate that azelaic acid may exert an anti-inflammatory effect by reducing the formation of pro-inflammatory, reactive oxygen species.

In the two vehicle controlled 12 week clinical studies in papulopustular rosacea, Finacea Gel was statistically significantly superior to its vehicle with regard to the reduction in inflammatory lesions, Investigator’s Global Assessment, overall rating of improvement and with regard to improvement of erythema.

In the clinical study with the active comparator metronidazole 0.75 % gel in papulopustular rosacea, Finacea Gel showed significant superiority with regard to lesion count reduction (72.7 % versus 55.8 %), overall rating of improvement and with regard to improvement of erythema (56 % versus 42 %). The rate of cutaneous adverse events, which in most cases were mild to moderate, was 25.8 % with Finacea Gel and 7.1 % with metronidazole 0.75 % gel.

There was no noticeable effect on the teleangiectasias in the three clinical studies.

5.2 Pharmacokinetic properties

Azelaic acid penetrates into all layers of the skin after topical application of the gel. Penetration is faster into damaged skin than into intact skin. A total of 3.6 % of the dose applied was absorbed percutaneously after a single topical application of 1 g azelaic acid (administered as 5 g Skinoren 20 % Cream). Clinical investigations in acne patients indicated similar absorption rates of azelaic acid from Finacea Gel and Skinoren Cream.

A portion of the azelaic acid absorbed through the skin is excreted in unchanged form with the urine. The remaining portion is broken down by P-oxidation into dicarboxylic acids with shorter chain length (C7, C5), which have likewise been found in the urine.

Steady-state plasma levels of azelaic acid in rosacea patients after 8 weeks twice daily treatment with Finacea Gel were within the range also observed in volunteers and acne patients on normal diets. This indicates that the extent of percutaneous absorption of azelaic acid following twice daily application of Finacea Gel does not alter the systemic burden of azelaic acid derived from dietary and endogenous sources.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

If azelaic acid came into contact with the eyes of monkeys and rabbits, signs of moderate to severe irritation became evident. Therefore, contact with the eyes should be avoided.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lecithin

Triglycerides (medium chain) Polysorbate 80

Propylene glycol Carbomer 980 Sodium hydroxide Disodium edetate Purified water Benzoic acid (E210)

6.2    Incompatibilities

Not applicable

6.3    Shelf life

3 years

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

Aluminium tube with internal epoxide coating and polyethylene screw cap.

Tubes of 5, 30, 50, 2 x 50 g.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Bayer plc Bayer House Strawberry Hill Newbury

Berkshire RG14 1JA United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 0010/0646

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

03/07/2007

10    DATE OF REVISION OF THE TEXT

27/06/2014