SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

BETESIL 2.250 mg medicated plaster.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 7.5 cm x 10 cm medicated plaster contains:

2.250 mg of betamethasone valerate (corresponding to 1.845 mg of betamethasone).

Excipients with known effect:

Methyl parahydroxybenzoate (2.250 mg)

Propyl parahydroxybenzoate (1.125 mg)

For the full list of excipients, see section 6.

3    PHARMACEUTICAL FORM

Medicated plaster.

Colourless plaster.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

BETESIL is indicated in adults.

Treatment of inflammatory skin disorders which do not respond to treatment with less potent corticosteroids, such as eczema, lichenification, lichen planus, granuloma annulare, palmoplantar pustulosis and mycosis fungoides.

Due to its particular pharmaceutical form, BETESIL is suitable for chronic plaque psoriasis localized in difficult to treat areas (e.g. knees, elbows and anterior face of the tibia on an area not greater than 5% of the body surface).

4.2    Posology and method of administration

Posology

Apply the medicated plaster to the skin area to be treated once a day. Do not exceed the maximum daily dose of six medicated plasters and the maximum treatment period of 30 days.

A new medicated plaster must be applied every 24 hours. It is also advisable to wait at least 30 minutes between one application and the next.

Once an appreciable improvement has been obtained, you can discontinue the application and possibly continue the treatment with a less potent corticosteroid.

Paediatric population

The safety and efficacy of BETESIL in children aged <18 years have not yet been established.

Method of administration

Precautions to be taken before handling or administering the medicinal product Cleanse and carefully dry the area to be treated before each application so that the medicated plaster adheres well to the skin.

Open the sachet containing the medicated plaster and cut the plaster, if necessary, so that it fits the area to be treated. Peel off the protective film and apply the adhesive medicated part to the area concerned.

Any unused part of the plaster should be put back into the sachet so that it keeps and can be used at the next application (see section 6.3).

The medicated plaster must not be removed and reused.

Once the medicated plaster has been applied, the skin must not come in contact with water. It is advisable to take a bath or have a shower between applications. Furthermore, if the medicated plaster is applied to particularly mobile parts (e.g. an elbow or knee) and its edges start to lift, it is advisable to apply the adhesive strips for securing dressings included in the medicinal product pack .

Never cover the medicated plaster completely with occlusive material or dressing.

4.3 Contraindications

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

Cutaneous tuberculosis and viral skin infections (including vaccinia pustules, herpes zoster and herpes simplex). Exudative lesions and primary skin infections caused by fungi or bacteria. Acne, acne rosacea, perioral dermatitis, skin ulcers, burns and frostbite.

Do not apply to face.

4.4 Special warnings and precautions for use

In general, use of topical corticosteroids on large areas of the body and for prolonged periods, as well as the use of occlusive dressing can cause a temporary suppression of the hypothalamus-pituitary-adrenal axis, leading to secondary hypoadrenalism and adrenal hypercorticism, including the Cushing’s syndrome. In these situations, treatment should be discontinued gradually and under strict control of a doctor due to the risk of acute adrenal insufficiency.

Sudden withdrawal of the treatment in psoriatic patients, may also lead to symptoms exacerbation or generalized pustular psoriasis.

Prolonged use of BETESIL in diffuse psoriasis (except for the treatment of isolated plaques) or diffuse eczema or application on lesions located in skin folds is not recommended, as these conditions may increase systemic absorption. The use of occlusive bandages, especially with plastic material, may increase this effect. The symptoms of this are: facial redness, weight changes (fat increase in body and face and loss in legs and arms), reddish streaks on stomach, headache, menstrual alterations, or an increase in unwanted face and body hair. In this regard, it is known that certain skin areas (face, eyelids, armpits, scalp and scrotum) absorb more easily than others (skin on the knees, elbows, palms of the hands and feet on soles).

Application of topical medicinal products, especially if prolonged, may give rise to hypersensitivity reaction. Skin atrophy has also been reported after three-week treatment periods.

In case of drug intolerance, for example if skin irritation or contact dermatitis occur during treatment, it is necessary to stop the medicated plaster application and start suitable treatment (see section 4.8 “Undesirable effects”).

Corticosteroids may affect the results of the nitroblue tetrazolium test (NBT) for diagnosing bacterial infections by producing false negatives.

Medicinal products containing corticosteroids must be used with caution in patients with impaired immune system function (T-lymphocytes) or in those being treated with immunosuppressive therapy.

The product contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause hypersensitivity reactions (possibly delayed).

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

At recommended doses, betamethasone valerate for topical use is not known to cause medically significant drug interactions. BETESIL did not show significant systemic absorption of betamethasone valerate.

4.6 Fertility, pregnancy and lactation

Pregnancy

Topical administration of corticosteroids to pregnant laboratory animals may cause impairment of foetal maturation. The importance of this preclinical data has not been evaluated in humans: however, topical steroids must not be used in pregnant women on large areas of skin and specifically, in large quantities or for long period of time. Therefore, this medicinal product must only be used in case of need and under direct medical control, after having assessed the real benefits for the mother against the possible risks for the foetus and having evaluated the treatment period and the size of the skin area to be treated.

Breast-feeding

Systemic corticosteroids are excreted in human milk.

It is unknown whether topical corticosteroids are excreted in human milk. Therefore topical corticosteroids should be used with caution also in nursing women and should not be applied to the breast.

4.7    Effects on ability to drive and use machines

BETESIL has no or negligible influence on the ability to drive and use machine.

4.8    Undesirable effects

The commonly reported adverse reactions are skin and subcutaneous tissue disorders, occurring in about 15% of patients treated. These undesirable effects are mainly due to the pharmacological effects of the medicinal product. They are local effects on the skin in the plaster application area. No systemic effects have been observed.

The following list of adverse reactions has been observed during controlled clinical trials.

Reported adverse reactions have been classified according to their frequency of observation using the following 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) and not known when cannot be estimated from the available data.

All cases reported were found to be common. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Skin and subcutaneous	Common	Skin atrophy
tissue disorders		Telangiectasia
		Pustules
		Papules
		Furuncle
		Erythema
		Pruritus
		Skin erosion

Other undesirable reactions not observed with BETESIL, but reported with topical corticosteroids are: contact dermatitis, hypersensitivity, oedema, purpura, striae atrophicae, dry skin, skin exfoliation, capillary fragility, skin irritation, hypertrichosis, hyperaesthesia, perioral dermatitis, burning or stretching sensation, folliculitis and skin hypopigmentation.

The use of topical corticosteroids on large areas of the body and for long periods, as well as the use of occlusive dressing can cause temporary suppression of the hypothalamus-pituitary-adrenal axis, leading to secondary hypoadrenalism and adrenal hypercorticism, including the Cushing’s syndrome. In these situations, treatment should be discontinued gradually and under strict control of a doctor due to the risk of acute adrenal insufficiency.

Sudden withdrawal of the treatment in psoriatic patients may also lead to symptoms exacerbation or generalized pustular psoriasis (see section 4.4 “Special warnings and precautions for use”).

Hypersensitivity reactions to occlusive plastic material have been observed rarely.

4.9 Overdose

No case of overdose has been reported.

Due to the product characteristics and the route of administration, the occurrence of symptoms and signs of corticosteroid overdose is unlikely.

However, prolonged use of topical corticosteroids may cause the temporary suppression of the hypothalamus-pituitary-adrenal axis, leading to secondary hypoadrenalism. Adrenal hypercorticism symptoms spontaneously reverse and their treatment is symptomatic. If necessary, act to restore the hydroelectrolytic balance. In the event of chronic toxicity, remove the corticosteroid from the organism slowly.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Corticosteroids, dermatological products: active corticosteroids (group III). ATC code: D07AC01.

Betamethasone valerate for topical application is active in the treatment of dermatosis, which responds to corticosteroids, due to its anti-inflammatory, antipruriginous and vasoconstrictor action.

5.2 Pharmacokinetic properties

Corticosteroids applied to the skin are mainly held back by the stratum corneum, and only a small part reaches the dermis where they can be absorbed. Several factors may however favour greater absorption: the location and area of the skin to be treated, the type of lesion, the treatment duration and any occlusive dressing.

In a comparative study conducted in healthy volunteers in whom 6 medicated plasters a day or an equivalent amount of cream were applied during 21 consecutive days, the levels of betamethasone (BM) measured in blood after 4 and 21 days were measurable in 11 out of 17 of the medicated plaster group and in 4 out of 10 in the cream group (LOQ= 50pg/mL). When measurable, BM blood levels in the subjects receiving the medicated plasters appeared to be slightly higher as compared to what measured in those treated with the cream. However, this difference in terms of systemic exposure had no impact on the HPA-axis function, since both the cortisol 24-h profile and the cortisol increase following ACTH stimulation test, evaluated in these same subjects, were not modified after 4 or 21 days of treatment as compared to baseline. Betamethasone valerate is mainly metabolized in the liver, where it is inactivated. It is then conjugated in the liver and kidneys with sulphate or glucuronic acid and excreted in urine.

5.3 Preclinical safety data

There are no significant data from preclinical trials, which may be relevant to physicians other than those already reported in other sections of the Summary of Product Characteristics.

6.1    List of excipients

Plaster: unwoven cloth (polypropylene/polyethylene and rayon fibres) laminated with an ethylene-methyl methacrylate copolymer film.

Adhesive layer: sodium hyaluronate, 1,3-butylene glycol, glycerol, disodium edetate, tartaric acid, aluminium glycinate, polyacrylic acid, sodium polyacrylate, hydroxypropylcellulose, carmellose sodium, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), purified water.

Protective film: polyethylene terephthalate film.

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

3 years.

After opening the sachet: 1 month.

6.4    Special precautions for    storage

Do not store above 25 °C.

Store the medicated plaster in its original sachet in order to preserve its integrity.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5    Nature and contents    of    container

Boxes: 4 medicated plasters / 8 medicated plasters / 16 medicated plasters Each medicated plaster is packed individually in a

paper/polyethylene/aluminium/ethylene-methacrylic acid copolymer sachet. Each box includes adhesive strips for securing dressings (medical device).

Not all pack sizes may be marketed

6.6 Special precautions for disposal

Used medicated plasters must not be flushed down toilets.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

IBSA Farmaceutici Italia S.r.I.

Via Martiri di Cefalonia 2, 26900 Lodi-Italy

8    MARKETING AUTHORISATION NUMBER

PL 21039 /0009

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorization: 12 /03/2007 Date of latest renewal: 09/10/2011

10 DATE OF REVISION OF THE TEXT

30/01/2013