SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Betamethasone Valerate 0.1%w/w Cream

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

0.1% betamethasone B.P. as the valerate ester

3.    PHARMACEUTICAL FORM

Cream.

4.    Clinical Particulars

4.1    Therapeutic indications

Severe inflammatory skin disorders such as eczema in patients unresponsive to less potent corticosteroids.

4.2 Posology and method of administration

Route of administration: Cutaneous

Creams are especially appropriate for moist or weeping surfaces.

Apply thinly and gently rub in using only enough to cover the entire affected area once or twice daily for up to 4 weeks until improvement occurs, then reduce the frequency of application or change the treatment to a less potent preparation.

Allow adequate time for absorption after each application before applying an emollient.

In the more resistant lesions, such as the thickened plaques of psoriasis on elbows and knees, the effect of betamethasone valerate can be enhanced, if necessary, by occluding the treatment area with polythene film. Overnight occlusion only is usually adequate to bring about a satisfactory response in such lesions; thereafter, improvement can usually be maintained by regular application without occlusion.

If the condition worsens or does not improve within 2-4 weeks, treatment and diagnosis should be re-evaluated.

Therapy with betamethasone valerate should be gradually discontinued once control is achieved and an emollient continued as maintenance therapy.

Rebound of pre-existing dermatoses can occur with abrupt discontinuation of betamethasone valerate.

Recalcitrant dermatoses

Patients who frequently relapse

Once an acute episode has been treated effectively with a continuous course of topical corticosteroid, intermittent dosing (apply once a day twice a week without occlusion) may be considered. This has been shown to be helpful in reducing the frequency of relapse.

Application should be continued to all previously affected sites or to known sites of potential relapse. This regimen should be combined with routine daily use of emollients. The condition and the benefits and risks of continued treatment must be re-evaluated on a regular basis.

Paediatric population

Betamethasone valerate is contraindicated in children under one year of age.

Children are more likely to develop local and systemic side effects of topical corticosteroids and, in general, require shorter courses and less potent agents than adults; therefore, courses should be limited to five days and occlusion should not be used.

Care should be taken when using betamethasone valerate to ensure the amount applied is the minimum that provides therapeutic benefit.

Elderly

Clinical studies have not identified differences in responses between the elderly and younger patients. The greater frequency of decreased hepatic or renal function in the elderly may delay elimination if systemic absorption occurs. Therefore the minimum quantity should be used for the shortest duration to achieve the desired clinical benefit.

Renal / Hepatic Impairment

In case of systemic absorption (when application is over a large surface area for a prolonged period) metabolism and elimination may be delayed therefore increasing the risk of systemic toxicity. Therefore the minimum quantity should be used for the shortest duration to achieve the desired clinical benefit.

4.3    Contraindications

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

The following conditions should not be treated with betamethasone valerate:

-Untreated cutaneous infections

-Rosacea

-Acne vulgaris

-Pruritus without inflammation -Perianal and genital pruritus -Perioral dermatitis

Betamethasone valerate is contraindicated in dermatoses in infants under one year of age, including dermatitis

4.4    Special Warnings And Special Precautions For Use

Hypersensitivity reactions

Betamethasone valerate should be used with caution in patients with a history of local hypersensitivity to other corticosteroids. Local hypersensitivity reactions (see section 4.8) may resemble symptoms of the condition under treatment.

Systemic effects

Long-term continuous topical therapy should be avoided where possible, particularly in infants and children, as reversible hypothalamic-pituitary-adrenal (HPA) suppression leading to glucocorticoid insufficiency, with or without clinical features of Cushing’s syndrome/hypercortisolism, can occur even without occlusion. In this situation, topical steroids should be discontinued gradually under medical supervision because of the risk of adrenal insufficiency (see sections 4.8 and 4.9).

Risk factors for increased systemic effects are:

-Potency and formulation of topical steroid -Duration of exposure -Application to a large surface area

-Use on occluded areas of skin e.g. on intertriginous areas or under occlusive dressings (in infants the nappy may act as an occlusive dressing)

-Increasing hydration of the stratum corneum -Use on thin skin areas such as the face

-Use on broken skin or other conditions where the skin barrier may be impaired -In comparison with adults, children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic adverse effects. This is because children have an immature skin barrier and a greater surface area to body weight ratio compared with adults.

Use in psoriasis

Topical corticosteroids should be avoided or given only under specialist supervision in psoriasis for a number of reasons including rebound relapses, development of tolerance, risk of generalised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin.

Application to the face or eyelids

Topical corticosteroids may cause skin atrophy, especially on thin skin areas such as the face or flexures, and may cause acne or perioral dermatitis when used on the face. Potent steroids such as betamethasone valerate 0.1% should not be applied to the face unless the patient is under specialist supervision.

If used on the face, courses should be limited to five days.

If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye, as glaucoma might result.

Paediatric population

If used in childhood, courses should be limited to five days and occlusion should not be used (see below). Long-term continuous topical corticosteroid therapy should be

avoided where possible as adrenal suppression can occur.

Use with occlusive dressings

Use of occlusive dressings, including nappies on infants, increase absorption of topical corticosteroids, with increased risk of systemic side effects (see also Concomitant infection).

Concomitant infection

Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions that have become infected. Any spread of infection requires withdrawal of topical corticosteroid therapy and systemic administration of antimicrobial agents. Bacterial infection is encouraged by the warm, moist conditions induced by occlusive dressings, and so the skin should be cleansed before a fresh dressing is applied.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat the dermatitis around chronic leg ulcers. However, this use may be associated with a higher incidence of local hypersensitivity reactions and an increased risk of local infection.

Potency

The least potent corticosteroid that will control the disease should be selected.

4.5 Interactions with other medicinal products and other forms of interaction

None known.

4.6 Pregnancy and lactation

There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intra-uterine growth retardation. There may be a very small risk of such effects in the human foetus, and it is therefore advisable to avoid the extensive use of betamethasone in pregnancy.

4.7 Effects on ability to drive and use machines

Not applicable.

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common ( > 1/10), common ( > 1/100 and < 1/10), uncommon ( > 1/1000 and < 1/100), rare ( > 1/10,000 and < 1/1000) and very rare ( < 1/10,000) including isolated reports.

Infections and infestations Very rare: Opportunistic infection

Immune system disorders:

Very rare: Hypersensitivity, generalised rash.

If signs of hypersensitivity appear, application should stop immediately.

Endocrine disorders:

Very rare: Features of Cushing’s syndrome (moon face, central obesity, delayed weight gain/growth retardation in children, osteoporosis, hyperglycaemia/glycosuria, glaucoma, cataract, hypertension, increased weight/obesity, decreased endogenous cortisol levels, alopecia, trichorrhexia).

As with other topical corticosteroids, prolonged use of large amounts or treatment of extensive areas can result in sufficient systemic absorption to produce suppression of the hypothalamic-pituitary-adrenal axis and the clinical features of Cushing’s syndrome (see section 4.4). These effects are more likely to occur in infants and children, and if occlusive dressings are used. In infants the nappy may act as an occlusive dressing.

Eye disorders:

Rare cases of glaucoma have been reported following the use of topical steroids in the periorbital region (see section 4.4).

Skin and subcutaneous tissue disorders:

Common: Local skin burning and pruritus.

Very rare: Local atrophic changes in the skin such as thinning, irreversible striae or telangiectasia may be caused by prolonged and intensive treatment with potent corticosteroid preparations, particularly when occlusive dressings are used or when skin folds are involved.

Allergic contact dermatitis/dermatitis, erythema, rash, urticaria, perioral dermatitis or acne, hypertrichosis, pigmentation changes and exacerbation of underlying symptoms have also been reported.

In rare instances, treatment of psoriasis with corticosteroids (or its withdrawal) is thought to have provoked the pustular form of the disease (see section 4.4).

Reporting of suspected 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

Acute overdose is very unlikely to occur. However, in the case of chronic overdose or misuse the features of Cushing’s syndrome may appear and in this situation topical

steroids should be discontinued gradually under medical supervision (see section 4.4).

5.1    Pharmacodynamic properties ATC code

D07AC Corticosteroids, potent (group III)

Mechanism of action

Topical corticosteroids act as anti-inflammatory agents via multiple mechanisms to inhibit late phase allergic reactions including decreasing the density of mast cells, decreasing chemotaxis and activation of eosinophils, decreasing cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibiting the metabolism of arachidonic acid.

Pharmacodynamic effects

Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties.

5.2    Pharmacokinetic properties Absorption

Topical corticosteroids can be systemically absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.

Distribution

The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary because circulating levels are well below the level of detection.

Metabolism

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.

Elimination

Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

5.3    Preclinical safety data Reproductive toxicity

Subcutaneous administration of betamethasone valerate to mice or rats at doses >0.1 mg/kg/day or rabbits at doses >12 micrograms/kg/day during pregnancy produced foetal abnormalities including cleft palate and intrauterine growth retardation.

The effect on fertility of betamethasone valerate has not been evaluated in animals.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Chlorocresol, liquid paraffin, cetostearyl alcohol, cetomacrogol 1000, propylene glycol, sodium phosphate, citric acid and purified water.

6.2    Incompatibilities

None.

6.3    Shelf life

Two (2) years.

6.4    Special precautions for storage

Do not store above 25°C. Store in the original container.

6.5    Nature and contents of container

Tubes containing 5g, 15g or 30g, or 100g Polypropylene jars containing 100 or 500g.

6.6    Special precautions for disposal

Not applicable.

7    MARKETING AUTHORISATION HOLDER

Manx Healthcare Limited Taylor Group House Wedgnock Lane Warwick CV34 5YA United Kingdom

8.    MARKETING AUTHORISATION NUMBER

PL 14251/0009

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

27 November 1998/21 December 2010

10 DATE OF REVISION OF THE TEXT

04/04/2014