Betnovate Cream

Betamethasone Valerate BP 0.122% ^W/_W

Aqueous Cream

Betamethasone valerate is an active topical corticosteroid which produces a rapid response in those inflammatory dermatoses that are normally responsive to topical corticosteroid therapy, and is often effective in the less responsive conditions such as psoriasis.

Betnovate preparations are indicated for the treatment of eczema in children and adults, including atopic and discoid eczemas, prurigo nodularis, psoriasis (excluding widespread plaque psoriasis); neurodermatoses, including lichen simplex, lichen planus; seborrhoeic dermatitis; contact sensitivity reactions; discoid lupus erythematosus and they may be used as an adjunct to systemic steroid therapy in generalised erythroderma.

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.

Children

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.

Hypersensitivity to the active substance or any of the excipients in the product.

The following conditions should not be treated with betamethasone valerate:

• Untreated cutaneous infections

o Rosacea

o Acne vulgaris

o Pruritus without inflammation

o Perianal and genital pruritus

o Perioral dermatitis

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

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.

Manifestations of hypercortisolism (Cushing's syndrome) and reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to glucocorticosteroid insufficiency, can occur in some individuals as a result of increased systemic absorption of topical steroids. If either of the above are observed, withdraw the drug gradually by reducing the frequency of application, or by substituting a less potent corticosteroid. Abrupt withdrawal of treatment may result in glucocorticosteroid insufficiency (see section 4.8).

Risk factors for increased systemic effects are:

o Potency and formulation of topical steroid

o Duration of exposure

o Application to a large surface area

o 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)

o Increasing hydration of the stratum corneum

o Use on thin skin areas such as the face

o Use on broken skin or other conditions where the skin barrier may be impaired

o 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.

Children

In infants and children under 12 years of age, treatment courses should be limited to five days and occlusion should not be used; long-term continuous topical corticosteroid therapy should be avoided where possible, as adrenal suppression can occur.

Infection risk with occlusion

Bacterial infection is encouraged by the warm, moist conditions within skin folds or caused by occlusive dressings. When using occlusive dressings, the skin should be cleansed before a fresh dressing is applied.

Use in Psoriasis

Topical corticosteroids should be used with caution in psoriasis as rebound relapses, development of tolerances, risk of generalised pustular psoriasis and development of local or systemic toxicity due to impaired barrier function of the skin have been reported in some cases. If used in psoriasis careful patient supervision is important.

Application to the face

Prolonged application to the face is undesirable as this area is more susceptible to atrophic changes; therefore, treatment courses should be limited to five days and occlusion should not be used.

Application to the eyelids

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

Concomitant infection

Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions which have become infected. Any spread of infection requires withdrawal of topical corticosteroid therapy and administration of appropriate antimicrobial therapy.

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 occurrence of local hypersensitivity reactions and an increased risk of local infection.

Co-administered drugs that can inhibit CYP3A4 (e.g. ritonavir, itraconazole) have been shown to inhibit the metabolism of corticosteroids leading to increased systemic exposure. The extent to which this interaction is clinically relevant depends on the dose and route of administration of the corticosteroids and the potency of the CYP3A4 inhibitor.

Fertility

There are no data in humans to evaluate the effect of topical corticosteroids on fertility.

Pregnancy

There are limited data from the use of betamethasone valerate in pregnant women.

Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development. (see section 5.3).

The relevance of this finding to humans has not been established; however, administration of betamethasone valerate during pregnancy should only be considered if the expected benefit to the mother outweighs the risk to the foetus. The minimum quantity should be used for the minimum duration.

Lactation

The safe use of topical corticosteroids during lactation has not been established.

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Administration of betamethasone valerate during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.

If used during lactation betamethasone valerate should not be applied to the breasts to avoid accidental ingestion by the infant.

There have been no studies to investigate the effect of betamethasone valerate on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated from the adverse reaction profile of topical betamethasone valerate.

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. Very common, common and uncommon events were generally determined from clinical trial data. The background rates in placebo and comparator groups were not taken into account when assigning frequency categories to adverse events derived from clinical trial data, since these rates were generally comparable to those in the active treatment group. Rare and very rare events were generally determined from spontaneous data.

Immune system disorders

If signs of hypersensitivity appear, application should stop immediately.

Endocrine disorders

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 HPA axis and the clinical features of Cushing's syndrome (see Section 4.4 Special Warnings and Precautions for use). These effects are more likely to occur in infants and children, and if occlusive dressings are used. In infants the napkin may act as an occlusive dressing.

Skin and subcutaneous tissue disorders

Symptoms and signs

Topically applied betamethasone valerate may be absorbed in sufficient amounts to produce systemic effects. Acute overdosage is very unlikely to occur, however, in the case of chronic overdosage or misuse the features of hypercortisolism may occur (see section 4.8).

Treatment

In the event of overdose, betamethasone valerate should be withdrawn gradually by reducing the frequency of application, or by substituting a less potent corticosteroid because of the risk of glucocorticosteroid insufficiency.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Betamethasone valerate is an active corticosteroid with topical anti-inflammatory activity.

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.

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.

None known.

Store below 25°C.

15gm, 30gm and 100gm collapsible aluminium tubes internally coated with an epoxy resin based lacquer and closed with a cap.

500mg opaque high density polythene pots with black urea formaldehyde screw caps having a steran faced wad.

Not all pack sizes may be marketed

No special instructions.

Glaxo Wellcome UK Ltd.,

T/A GlaxoSmithKline UK

Stockley Park West,

Uxbridge,

Middlesex UB11 1BT

PL10949/0014

24 October 1997

17^th April 2012