SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Clobavate 0.05% w/w Ointment

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Contains clobetasone butyrate 0.05% w/w (0.5 mg/g)

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Ointment

Opaque ointment.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Clobavate is suitable for the treatment of corticosteroid sensitive dermatoses, including atopic eczema, photodermatitis, otitis externa, primary irritant and allergic dermatitis (including napkin rash), intertrigo, prurigo nodularis, seborrhoeic dermatitis and insect bite reactions.

Clobavate may be used as maintenance therapy between courses of one of the more active topical steroids.

4.2 Posology and method of administration

Method of administration: Topical application Adults, Elderly, Children and Infants Ointment

Ointments are especially appropriate for dry, lichenified or scaly lesions. Apply thinly and gently rub in using only enough to cover the entire affected area once or twice a day 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.

Therapy with topical corticosteroids 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 topical corticosteroids especially with potent preparations.

Duration of treatment for adults and elderly

Continuous daily treatment for longer than four weeks is not recommended. If the condition worsens or does not improve within four weeks, treatment and diagnosis should be re-evaluated.

Paediatric population

Children are more likely to develop local and systemic adverse reactions of topical corticosteroids and, in general, require shorter courses and less potent agents than adults.

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

Duration of treatment for children and infants

If the condition worsens or does not improve within 7 days, treatment should be withdrawn and the child re-evaluated. Once the condition has been controlled, the frequency of application should be reduced to the lowest effective dose for the shortest possible time.

Continuous daily treatment for longer than four weeks is not recommended.

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

Use in the presence of untreated infections of bacterial, tuberculous, treponemal, viral or fungal origin.

Use with occlusive covering in children under one year of age.

Hypersensitivity to the active ingredient or to any of the excipients.

Use in acne vulgaris, rosacea or in perioral dermatoses.

Use in pruritus without inflammation.

4.4 Special warnings and precautions for use

Although generally regarded as safe, even for long-term administration in adults, there is a potential for overdosage, and in infants and children this may result in adrenal suppression. Extreme caution is required in dermatoses in such patients and treatment should not normally exceed seven days. In infants, the napkin may act as an occlusive dressing, and increase absorption.

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 systemic administration of antimicrobial agents.

Application to the face

As with all corticosteroids, prolonged application to the face is undesirable as this area is more susceptible to atrophic changes.

Topical corticosteroids may be hazardous 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. If used in psoriasis, careful patient supervision is important.

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.

Clobavate 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:

•    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 and infants 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

When clobetasone is used in the treatment of dermatoses in children, extreme caution is required and treatment should not normally exceed seven days; shorter courses of treatment and less potent agents than those used for adults are required.

In infants and children under 12 years of age, long-term continuous topical corticosteroid therapy should be avoided where possible, as adrenal suppression is more likely to 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.

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.

Accidental ingestion

For external use only. This and all medication should be kept out of the reach of children. In case of accidental ingestion, professional assistance should be sought or a national poison control centre contacted immediately (see section 4.9).

4.5 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 duration of administration of the corticosteroids and the potency of the CYP3A4 inhibitor.

4.6 Fertility, pregnancy and lactation

Pregnancy:

There is inadequate evidence of safety in human pregnancy. Topical administration of corticosteroids to pregnant animals can cause abnormalities of fetal development including cleft palate and intra-uterine growth retardation. There might therefore be a very small risk of such effects in the human fetus.

This product should not be used during pregnancy, unless considered essential by the physician. The minimum quantity should be used for the minimum duration.

Lactation

It is unknown whether clobetasone butyrate is excreted in human breast milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from clobetasone butyrate therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

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

Fertility

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

4.7 Effects on ability to drive and use machines

There have been no studies to investigate the effect of clobetasone 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 clobetasone.

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), very rare (<1/10,000) and not known (cannot be estimated from the available data). 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 derived from spontaneous data.

Infections and Infestations Very rare : Opportunistic infection

Immune System Disorders

Very rare:    Hypersensitivity, generalised rash

Local hypersensitivity reactions such as erythema, rash, pruritus, urticaria, local skin burning and allergic contact dermatitis may occur at the site of application and may resemble symptoms of the condition under treatment.

In the unlikely event of signs of hypersensitivity appearing, application should stop immediately.

Endocrine Disorders

Very rare:    Hypothalamic-pituitary adrenal (HPA) axis suppression, adrenal

suppression (menstrual disorders, amenorrhoea, hirsutism, weight gain & increased appetite), Cushingoid features (moon face, central obesity, hirsutism, buffalo hump, flushing, ecchymoses, striae & acne), delayed weight gain/growth retardation in children, osteoporosis, glaucoma, hyperglycaemia/glucosuria, cataract, hypertension, increased weight/obesity, decreased endogenous cortisol levels

When large areas of the body are being treated with clobetasone 17-butyrate, it is possible that some patients will absorb sufficient steroid to cause transient adrenal suppression despite the low degree of systemic activity associated with clobetasone 17-butyrate.

Skin and Subcutaneous Tissue Disorders

Very rare: Allergic contact dermatitis, urticaria, skin atrophy*, pigmentation changes*, local skin burning, hypertrichosis, rash, pruritus, erythema

Local atrophic changes could possibly occur in situations where moisture increases absorption of clobetasone 17-butyrate, but only after prolonged use.

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

General Disorders and Administration Site Conditions

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 the national reporting system (see below):

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

Pharmacovigilence Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.img.ie

E-mail: imbpharmacovigilance@imb.ie

4.9 Overdose

Symptoms and signs

Topically applied clobetasone may be absorbed in sufficient amounts to produce systemic effects. Acute overdose is very unlikely to occur, however, in the case of chronic overdosage or misuse the features of hypercortisolism may appear.

Treatment

In the event of overdose, clobetasone 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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ATC Code: D07 AB01

Pharmacotherapeutic Group: Corticosteroid, moderately potent (group II)

Clobetasone butyrate is a topically active corticosteroid of moderate potency (UK Class II - 2-25 times as potent as hydrocortisone).

Clobetasone butyrate has little effect on hypothalamo-pituitary-adrenal function. This was so even when applied to adults in large amounts under whole body occlusion.

Clobetasone butyrate is less potent than other available corticosteroid preparations and has been shown not to suppress the hypothalamo-pituitary-adrenal axis in patients treated for psoriasis or eczema.

Pharmacological studies in man and animals have shown that clobetasone butyrate has a relatively high level of topical activity accompanied by a low level of systemic activity.

5.2 Pharmacokinetic properties

A single application of 30g clobetasone butyrate 0.05% ointment to eight patients resulted in a measurable rise in plasma clobetasone butyrate levels during the first three hours but then the levels gradually decreased. The maximum plasma level reached in the first three hours was 0.6ng/ml. This rise in levels was followed by a more gradual decline with plasma levels of clobetasone butyrate falling below 0.1ng/ml (the lower limit of the assay) after 72 hours. The normal diurnal variation in plasma cortisol levels was not affected by the application of clobetasone butyrate ointment.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber that are additional to those in other sections of the SmPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Liquid paraffin

White soft paraffin

6.2    Incompatibilities

Not applicable.

36 months

In-use shelf life: 3 months.

6.4 Special precautions for storage

Store in the original package in order to protect from light.

6.5    Nature and contents of container

Collapsible aluminum tubes internally coated with an epoxy resin based lacquer and closed with a polypropylene cap.

Pack sizes: 30g or 100g.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

Patients should be advised to wash their hands after applying Clobavate, unless it is the hands that are being treated.

7    MARKETING AUTHORISATION HOLDER

Auden Mckenzie (Pharma Division) Ltd

McKenzie House

Bury Street

Ruislip

Middlesex

HA4 7TL

UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 17507/0118

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DATE OF REVISION OF THE TEXT

10/02/2015