Cutivate Cream 0.05%.

Fluticasone Propionate (micronised) HSE 0.05% w/w.

Cream

Adults:

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses such as: eczema 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; an adjunct to systemic steroid therapy in generalised erythroderma; insect bite reactions; or prickly heat.

Children:

For children and infants aged three months and over who are unresponsive to lower potency corticosteroids Cutivate Cream is indicated for the relief of the inflammatory and pruritic manifestations of atopic dermatitis under the supervision of a specialist. Expert opinion should be sought prior to the use of Cutivate Cream in other corticosteroid responsive dermatoses in children.

Eczema/Dermatitis

For adults, children and infants aged three months and over, apply a thin film of Cutivate Cream to the affected skin areas once daily.

Other indications

Apply a thin film of Cutivate Cream to the affected skin areas twice daily

Duration of use :

Daily treatment should be continued until adequate control of the condition is achieved. Frequency of application should thereafter be reduced to the lowest effective dose.

When Cutivate is used in the treatment of children, if there is no improvement within 7 – 14 days, treatment should be withdrawn and the child re-evaluated. Once the condition has been controlled (usually within 7-14 days), frequency of application should be reduced to the lowest effective dose for the shortest possible time. Continuous daily treatment for longer than 4 weeks is not recommended

For topical administration.

Rosacea, acne vulgaris, perioral dermatitis, primary cutaneous viral infections (e.g. herpes simplex, chickenpox). Hypersensitivity to any of the ingredients. Perianal and genital pruritus. The use of fluticasone propionate skin preparations is not indicated in the treatment of primarily infected skin lesions caused by infection with fungi or bacteria. Dermatoses in infants under three months of age, including dermatitis and napkin eruptions.

Fluticasone propionate has a very low propensity for systemic absorption, nevertheless, prolonged application of high doses to large areas of body surface, especially in infants and small children, might lead to adrenal suppression. Children and infants have a greater surface area to body weight ratio compared with adults. Therefore, in comparison with adults, children and infants may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. Care should be taken when using Cutivate Cream to ensure the amount applied is the minimum that provides therapeutic benefit.

Long-term continuous use should be avoided in children and infants. The safety and efficacy of fluticasone propionate when used continuously for longer than 4 weeks has not been established.

The face, more than other areas of the body may exhibit atrophic changes after prolonged treatment with potent topical corticosteroids. This must be borne in mind when treating such conditions as psoriasis, discoid lupus erythematosus and severe eczema.

If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye so as to avoid the risk of local irritation or glaucoma.

Topical steroids 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 and referral to a dermatologist is required before using Cutivate Cream to treat psoriasis in children and infants.

Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions, which have become infected. Any 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 dressing, and so the skin should be cleansed before a fresh dressing is applied.

Cutivate Cream contains the excipient, imidurea, which releases traces of formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.

None known.

Pregnancy: Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development, but in humans there is no convincing evidence that systemic corticosteroids cause an increased incidence of congenital abnormalities. However, administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Lactation: The excretion of fluticasone propionate into human breast milk has not been investigated. When measurable, plasma levels were obtained in lactating laboratory rats following subcutaneous administration, there was evidence of fluticasone propionate in the breast milk. However plasma levels in patients following dermal application of fluticasone propionate at recommended doses are likely to be low.

When fluticasone propionate is used in breast feeding mothers, the therapeutic benefits must be weighed against the potential hazards to mother and baby.

None known.

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 derived from spontaneous data.

Infections and infestations

Very rare: Secondary infection.

Secondary infections, particularly when occlusive dressings are used or when skin folds are involved have been reported with corticosteroid use.

Immune system disorders

Very rare: Hypersensitivity.

If signs of hypersensitivity appear, application should stop immediately.

Endocrine disorders

Very rare: Features of hypercortisolism.

Prolonged use of large amounts of corticosteroids, or treatment of extensive areas, can result in sufficient systemic absorption to produce the features of hypercortisolism. This effect is more likely to occur in infants and children, and if occlusive dressings are used. In infants, the napkin may act as an occlusive dressing (See 4.4 Special Warnings and Special Precautions for Use).

Vascular disorders

Very rare: Dilation of superficial blood vessels.

Prolonged and intensive treatment with potent corticosteroid preparations may cause dilation of the superficial blood vessels.

Skin and subcutaneous tissue disorders

Common: Pruritus.

Uncommon: Local burning.

Very rare: Allergic contact dermatitis, exacerbation of signs and symptoms of dermatoses, pustular psoriasis. Prolonged and intensive treatment wih potent corticosteroid preparations may cause thinning, striae, hypertrichosis and hypopigmentation.

Treatment of psoriasis with a corticosteroid (or its withdrawal) may provoke the pustular form of the disease.

Acute overdosage is very unlikely to occur, however, in the case of chronic overdosage or misuse, the features of hypercortisolism may appear and in this situation, topical steroids should be discontinued gradually. However, because of the risk of acute adrenal suppression this should be done under medical supervision.

Fluticasone propionate is a glucocorticoid with high topical anti-inflammatory potency but low HPA-axis suppressive activity after dermal administration. It therefore has a therapeutic index which is greater than most of the commonly available steroids.

It shows high systemic glucocorticoid potency after subcutaneous administration but very weak oral activity, probably due to metabolic inactivation. In vitro studies show a strong affinity for, and agonist activity at, human glucocorticoid receptors.

Fluticasone propionate has no unexpected hormonal effects, and no overt, marked effects upon the central and peripheral nervous systems, the gastrointestinal system, or the cardiovascular or respiratory systems.

Pharmacokinetic data for the rat and dog indicate rapid elimination and extensive metabolic clearance. Bioavailability is very low after topical or oral administration, due to limited absorption through the skin or from the gastrointestinal tract, and because of extensive first-pass metabolism. Distribution studies have shown that only minute traces of orally administered compound reach the systemic circulation, and that any systemically-available radiolabel is rapidly eliminated in the bile and excreted in the faeces.

Fluticasone propionate does not persist in any tissue, and does not bind to melanin. The major route of metabolism is hydrolysis of the S-fluoromethyl carbothioate group, to yield a carboxylic acid (GR36264), which has very weak glucocorticoid or anti-inflammatory activity. In all test animal species, the route of excretion of radioactivity is independent of the route of administration of radiolabelled fluticasone propionate. Excretion is predominantly faecal and is essentially complete within 48 hours.

In man too, metabolic clearance is extensive, and elimination is consequently rapid. Thus drug entering the systemic circulation via the skin, will be rapidly inactivated. Oral bioavailability approaches zero, due to poor absorption and extensive first-pass metabolism. Therefore systemic exposure to any ingestion of the topical formulation will be low.

Reproductive studies suggest that administration of corticosteroids to pregnant animals can result in abnormalities of foetal development including cleft palate/lip. However, in humans, there is no convincing evidence of congenital abnormalities, such as cleft palate or lip.

Studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, fertility and general reproductive performance revealed no special hazard for humans, other than that anticipated for a potent steroid.

Liquid Paraffin

Cetostearyl Alcohol

Isopropyl Myristate

Cetomacrogol 1000

Propylene Glycol

Imidurea

Sodium Phosphate

Citric Acid Monohydrate

Purified Water

None reported.

24 months.

Store below 30°C.

15g, 30g, 50g and 100g collapsible internally-laquered, blind-end aluminium tubes, with latex bands and closed with polypropylene caps.

Not all pack sizes may be marketed

No special instructions.

Glaxo Wellcome UK Ltd T/A Glaxo Laboratories

and / or GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex, UB11 1BT.

PL 10949/0013.

30 May 2008

30 May 2008

POM.