BETNOVATE OINTMENT

SUMMARY OF PRODUCT CHARACTERISTICS

NAME OF THE MEDICINAL PRODUCT

Betnovate Ointment

QUALITATIVE AND QUANTITATIVE COMPOSITION

Betamethasone Valerate B.P. 0.122% w/w

Equivalent to 0.1 w/w betamethasone

For the full list of excipients, see section 6.1

PHARMACEUTICAL FORM

Ointment

CLINICAL PARTICULARS

Therapeutic indications

Betamethasone valerate is a potent topical corticosteroid indicated for adults, elderly

and children over 1 year for the relief of the inflammatory and pruritic manifestations

of steroid responsive dermatoses. These include the following:

Atopic dermatitis (including infantile atopic dermatitis)

Nummular dermatitis (discoid eczema)

Prurigo nodularis

Psoriasis (excluding widespread plaque psoriasis)

Lichen simplex chronicus (neurodermatitis) and lichen planus

Seborrhoeic dermatitis

Irritant or allergic contact dermatitis

Discoid lupus erythematosus

Adjunct to systemic steroid therapy in generalised erythroderma

Posology and method of administration

Route of administration: Cutaneous

Ointments are especially appropriate for dry, lichenified, scaly lesions.

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.

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 (viral, fungal and bacterial)

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.

Special warnings and precautions for use

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

hypercortisolism

(Cushing’s

syndrome)

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:

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.

Paediatric population

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.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a

patient presents with symptoms such as blurred vision or other visual disturbances,

the patient should be considered for referral to an ophthalmologist for evaluation of

possible causes which may include cataract, glaucoma or rare diseases such as central

serous chorioretinopathy (CSCR) which have been reported after use of systemic and

topical corticosteroids.

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.

Healthcare professionals should be aware that if this product comes into contact with

dressings, clothing and bedding, the fabric can be easily ignited with a naked flame.

Patients should be warned of this risk and advised to keep away from fire when using

this product.

Interaction with other medicinal products and other forms of interaction

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, pregnancy and lactation

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).

relevance

this

finding

humans

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

produce

detectable

amounts

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.

Effects on ability to drive and use machines

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.

Undesirable effects

Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and

by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100

and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000) and

very rare (<1/10,000), including isolated reports.

Post-marketing data

Infections and Infestations

Very rare Opportunistic infection

Immune System Disorders

Very rare Hypersensitivity, generalised rash

Endocrine Disorders

Very rare Hypothalamic-pituitary adrenal (HPA) axis suppression

Cushingoid features (e.g. moon face, central obesity), delayed weight gain/growth retardation

in children,

osteoporosis, glaucoma, hyperglycaemia/glucosuria,

cataract, hypertension, increased weight/obesity, decreased

endogenous cortisol levels, alopecia, trichorrhexis

Skin and Subcutaneous Tissue Disorders

Common Pruritus, local skin burning /skin pain

Very rare

Allergic contact dermatitis /dermatitis, erythema, rash,

urticaria, pustular psoriasis, skin thinning* / skin atrophy*, skin

wrinkling*, skin dryness*, striae*, telangiectasias*,

pigmentation changes*,hypertrichosis, exacerbation of

underlying symptoms

General Disorders and Administration Site Conditions

Very rare Application site irritation/pain

*Skin features secondary to local and/or systemic effects of hypothalamic-pituitary adrenal (HPA) axis

suppression.

Eye disorders

Not known

Vision, blurred (see also section 4.4)

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.

Any suspected adverse events should be reported to the Ministry of Health

according to the National Regulation by using an online form

https://sideeffects.health.gov.il/

Additionally, you should also report to GSK Israel (

il.safety@gsk.com

Overdose

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.

PHARMACOLOGICAL PROPERTIES

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.

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.

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.

PHARMACEUTICAL PARTICULARS

List of excipients

Liquid Paraffin

White Soft Paraffin

Incompatibilities

None known

Shelf life

The expiry date of the product is indicated on the label and packaging.

Special precautions for storage

Store below 30°C

Nature and contents of container

Betnovate Ointment:

15gm, 30 gm and 100 gm collapsible aluminium tubes internally coated with an

epoxy resin based lacquer and closed with a polypropylene cap.

Not all pack sizes may be marketed

Special precautions for disposal

No special requirements.

MARKETING AUTHORISATION HOLDER

Glaxo Operations (UK) Limited, Barnard Castle, UK

License Holder and Importer

GlaxoSmithKline (Israel) Ltd., 25 Basel St., Petach Tikva

License Number

017-04-24760

The format of this leaflet was determined by the Ministry of Health and its content was checked and

approved in February 2014

and updated according to the guidelines of the Ministry of Health in

October 2017

Bet Oin DR V1

©2019 GSK group of companies or its licensor

Trade marks are owned by or licensed to the GSK group of companies.