BETESIL 2,250 mg Emplâtre médic 8Sach/1

Betamethasone valerate........................................................................................................2,250 mg

Equivalent to betamethasone...................................................................................................... 1,845 mg

For a medicated plaster of 7,5 cm x 10 cm

Excipients with known effect: methyl parahydroxybenzoate (E218) (2,250 mg), propyl parahydroxybenzoate (E216) (1,125 mg).

BETESIL is indicated in adults only.

Treatment of inflammatory dermatoses that do not respond to corticosteroids of lower activity level, such as eczema, lichenification, lichen planus, granuloma annulare, palmoplantar pustulosis, and mycosis fungoides.

Due to its particular pharmaceutical form, BETESIL is suitable for treating mild to moderate chronic plaque psoriasis localised to hard-to-treat sites (knees, elbows and anterior surface of the tibia). Overall, the area treated with BETESIL must not exceed 5 % of the body surface area.

Dosage

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

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

When a noticeable improvement is obtained, you may stop applications and continue treatment with a corticosteroid of lower activity level.

Paediatric population

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

As no data are available, BETESIL must not be used in children aged less than 18 years.

Method of administration

Precautions to take before handling or applying the plaster:

Carefully clean and 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 matches the area to be treated. Remove the protective film and apply the adhesive part of the plaster to the affected area.

Any unused part of the plaster must be returned to the sachet for storage and for use at the next application (see section Shelf life).

Once applied, the medicated plaster must not be removed and reused.

Once the patch has been applied, the skin must not be wet. It is advised to take a bath or shower between applications.

Furthermore, if the medicated patch is applied to particularly mobile areas (elbow or knee) and the edges begin to come loose, it is advised to place a small piece of adhesive plaster supplied in the packaging only on the detached parts.

Do not apply to the face.

Never cover the medicated patch completely with an occlusive material or a dressing.

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
• Cutaneous tuberculosis and viral skin infections (including vaccinia pustules, herpes zoster and Herpes simplex).
• Weeping lesions and primary skin lesions caused by fungal or bacterial infections (for example syphilitic skin lesions).
• Acne, acne rosacea, perioral dermatitis, skin ulcers, burns and chilblains.

In general, the use of topical corticosteroids over an extensive body surface area and for prolonged periods, as well as the use of an occlusive dressing, may cause temporary suppression of the hypothalamic-pituitary axis, leading to secondary hypoadrenalism and adrenal hypercorticism, including Cushing's syndrome. In these situations, treatment must be discontinued gradually and under strict medical supervision due to the risk of acute adrenal insufficiency.

Abrupt discontinuation of treatment in psoriasis patients may also lead to an exacerbation of symptoms or to generalised pustular psoriasis.

Prolonged use of BETESIL is not recommended in cases of widespread psoriasis (except treatment of isolated plaques) or widespread eczema, or application to lesions located in skin folds, as these situations may promote systemic absorption. The use of occlusive dressings, in particular with plastic material, may increase this effect. The corresponding symptoms are: facial redness, weight change (weight gain in the body and face and loss in the legs and arms), reddish striae on the stomach (stretch marks), headaches, menstrual cycle disorders, or an undesirable increase in hair growth on the face and body.

Thus, it is known that certain skin surfaces (face, eyelids, armpits, scalp and scrotum) absorb more readily than others (skin of the knees, elbows, palms of the hands and soles of the feet).

The application of topical products, particularly if prolonged, may cause hypersensitivity reactions. Skin atrophy has also been reported after periods of three weeks of treatment.

In case of intolerance to the medicine, for example if skin irritation or contact dermatitis occurs during treatment, it is necessary to stop applying the patch and start appropriate treatment (see section Adverse effects).

Topical steroid withdrawal syndrome:

Continuous long-term or inappropriate use of topical corticosteroids may lead to the occurrence of a rebound effect after discontinuation of treatment (topical steroid withdrawal syndrome). A severe form of rebound effect may occur and take the form of dermatitis with intense redness, tingling and/or burning sensation, itching, skin desquamation, weeping pustules that may spread beyond the initially treated area.

It is more likely to occur when sensitive skin sites such as the face and folds are treated. In case of relapse within days or weeks after discontinuation of treatment, a withdrawal reaction should be suspected. Re-application should be done with caution: the advice of a specialist is recommended and other treatment options should be considered, where appropriate.

Visual disturbances may occur with systemic or local corticosteroid therapy. In case of blurred vision or the appearance of any other visual symptom during corticosteroid therapy, an ophthalmological examination is required to look for cataract, glaucoma, or rarer lesions such as central serous chorioretinopathy, as described with systemic or local administration of corticosteroids.

Corticosteroids may disturb the results of the NBT (nitroblue tetrazolium test) used for the diagnosis of bacterial infections, by producing false negatives.

Medicines containing corticosteroids should be used with caution in immunocompromised patients (T lymphocytes) or in patients receiving immunosuppressive treatment.

This medicine contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (which may be delayed).

No interaction studies have been performed.

At the recommended doses, topical betamethasone valerate is not likely to cause clinically significant drug interactions

BETESIL has not resulted in significant systemic absorption of betamethasone valerate

Pregnancy

There are little or no data on the use of betamethasone valerate in pregnant women. Animal studies have shown reproductive toxicity (see section Preclinical safety). BETESIL is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Systemic corticosteroids are excreted in human milk.

The passage of topical corticosteroids into human milk is not known.

Therefore topical corticosteroids should also be used with caution in breast-feeding women and should not be applied to the breast.

BETESIL has no or negligible effect on the ability to drive vehicles and use machines.

Frequent adverse effects are skin and subcutaneous tissue disorders occurring in approximately 15 % of treated patients. These adverse effects are mainly due to the pharmacological effects of the medicinal product. They are local skin effects at the site of application of the medicated plaster. No systemic effects have been observed.

The list of adverse effects below was observed during controlled clinical studies.

Reported adverse effects were classified by frequency of occurrence according to 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, frequency not known (cannot be estimated from the available data).

All reported cases were common. Within each frequency group, adverse effects are presented in order of decreasing seriousness.

Other adverse effects not observed with BETESIL but reported with topical corticosteroids are: contact dermatitis, hypersensitivity, oedema, purpura, striae, dry skin, desquamation, capillary fragility, skin irritation, hypertrichosis, hyperaesthesia, perioral dermatitis, burning or tightening sensation, folliculitis and skin depigmentation.

Use of topical corticosteroids over an extensive body surface area and for prolonged periods, as well as the use of an occlusive dressing, may cause temporary suppression of the hypothalamic-pituitary axis, leading to secondary hypoadrenalism and adrenal hypercorticism including Cushing's syndrome. In these situations, treatment must be discontinued gradually and under strict medical supervision due to the risk of acute adrenal insufficiency.

Abrupt withdrawal of treatment in psoriatic patients may also lead to an exacerbation of symptoms or to generalised pustular psoriasis (see section Warnings and precautions).

Cases of hypersensitivity to the occlusive plastic material have rarely been observed.

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 national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr

No cases of overdose have been reported.

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

However, prolonged use of topical corticosteroids may cause temporary suppression of the hypothalamic-pituitary axis, causing secondary adrenal insufficiency. Symptoms of hypercorticism are spontaneously reversible and their treatment is symptomatic. If necessary, restore the fluid and electrolyte balance. In cases of chronic toxicity, slowly eliminate the corticosteroid from the body.

Pharmacotherapeutic class: Corticosteroids, dermatological preparations: corticosteroids (group III), ATC code: D07AC01.

Betamethasone valerate, classified as a strongly active corticosteroid, is active in the treatment of corticosteroid-responsive dermatoses, owing to its anti-inflammatory, antipruritic and vasoconstrictive activity.

Absorption

When applied to the skin, corticosteroids are mainly retained in the stratum corneum, and only small amounts reach the dermis where they can be absorbed. However, several factors can favour their absorption: the treated site and its surface area, the type of lesion, the duration of treatment and any use of occlusive dressing.

In a comparative study conducted in healthy volunteers to whom 6 medicated plasters per day or an equivalent quantity of cream were applied for 21 consecutive days, blood levels of betamethasone (BM) measured after 4 and 21 days were measurable in 11 patients out of 17 in the medicated plaster group and in 4 patients out of 10 in the cream group (LOQ = 50 pg/mL).

When measurable, the blood level of BM was slightly higher in patients who had applied the medicated plaster compared with those treated with cream. However, this difference in systemic exposure had no impact on the functioning of the hypothalamic-pituitary-adrenal axis: the cortisol profile over 24 h and the increase in cortisol after an ACTH stimulation test, assessed in these same subjects, were not modified after 4 or 21 days of treatment, compared with baseline values.

Biotransformation

Betamethasone valerate is metabolised mainly in the liver, where it is inactivated. It is then sulfo- or glucurono-conjugated in the liver and kidney.

Elimination

Betamethasone valerate is excreted in the urine.

Toxicity following repeated oral administration was studied in rats and showed a slight decrease in body weight as well as a decrease in the number of lymphocytes, eosinophils and neutrophils.

No reproductive toxicology study has been conducted with betamethasone valerate. However, betamethasone disodium phosphate has been shown to be teratogenic in rats and rabbits after systemic treatment administered parenterally: the most frequent malformation was palatoschisis, also observed with other corticosteroids in animals.

No mutagenicity or genotoxicity of betamethasone valerate has been observed. Alterations of the skin, in particular thinning of the dermis and epidermis, were observed after repeated cutaneous applications in animals.

3 years.

After opening the sachet: 1 month.

Store at a temperature not exceeding 25 °C.

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

For storage conditions of the medicine after first opening, see section Shelf life.

Used plasters must not be disposed of in the toilet.

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