SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Dermovate-NN Ointment

Clobetasol propionate/neomycin sulphate/nystatin 0.5mg/5mg/100,000 IU/g Ointment

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

The ointment contains clobetasol propionate 0.05% w/w, neomycin sulphate 0.5% w/w and nystatin 100,000 units per gram.

3    PHARMACEUTICAL FORM

Ointment.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Clobetasol propionate is a highly active topical corticosteroid which is of particular value when used in short courses for the treatment of recalcitrant eczemas, neurodermatoses, and other conditions which do not respond satisfactorily to less active steroids.

Clobetasol/neomycin/nystatin Ointment is indicated in more resistant dermatoses such as recalcitrant eczemas and psoriasis (excluding widespread plaque psoriasis) where secondary bacterial or candidal infection is present, suspected or likely to occur, as when using occlusive dressings.

4.2 Posology and method of administration

Adults and children over 2 years: Apply sparingly to the affected area once or twice daily until improvement occurs. As with other highly-active topical steroid preparations therapy should be discontinued when control is achieved. In the more responsive conditions this may be within a few days.

In very resistant lesions, especially where there is hyperkeratosis, the antiinflammatory effects of Clobetasol/neomycin/nystatin Ointment can be enhanced, if necessary, by occluding the treatment area with polythene. Overnight occlusion only is usually adequate to bring about a satisfactory response, thereafter improvement can be usually maintained by application without occlusion.

Treatment should not be continued for more than 7 days without medical supervision. If a longer course is necessary, it is recommended that treatment should not be continued for more than 4 weeks without the patient’s condition being reviewed.

Repeat short courses of Clobetasol/neomycin/nystatin Ointment may be used to control exacerbations. If continuous steroid treatment is necessary, a less potent preparation should be used.

Dosage in Renal Impairment: Dosage should be reduced in patients with reduced renal function (see Special Warnings and Precautions for Use).

Elderly: Clobetasol/neomycin/nystatin Ointment is suitable for use in the elderly. Caution should be exercised in cases where a decrease in renal function exists and significant systemic absorption of neomycin sulphate may occur (See Special Warnings and Precautions for Use).

Children: Clobetasol/neomycin/nystatin Ointment is suitable for use in children (2 years and over) at the same dose as adults. A possibility of increased absorption exists in very young children, thus this ointment is not recommended for use in neonates and infants (younger than 2 years) (see Contraindications and Special Warnings and Precautions for Use).

For topical administration.

4.3 Contraindications

Rosacea, acne vulgaris and perioral dermatitis.

Primary cutaneous viral infections (e.g. herpes simplex, chickenpox).

Hypersensitivity to the preparations.

Use of Clobetasol/neomycin/nystatin skin preparations is not indicated in the treatment of primary infected skin lesions caused by infection with fungi (e.g. candidiasis, tinea), bacteria (e.g. impetigo), or yeast; secondary infections due to Pseudomonas or Proteus species; perianal and genital pruritus, dermatoses in children under 2 years of age, including dermatitis and napkin eruptions.

Preparations containing neomycin should not be used for the treatment of otitis externa when the eardrum is perforated, because of the risk of ototoxicity. Due to the known ototoxic and nephrotoxic potential of neomycin sulphate the use of this medicinal product in large quantities or on large areas for prolonged periods is not recommended in circumstances where significant systemic absorption may occur.

A possibility of increased absorption exists in very young children, therefore Clobetasol/neomycin/nystatin Ointment is not recommended for use in neonates and infants (up to 2 years). In neonates and infants, absorption by immature skin may be enhanced, and renal function may be immature.

4.4 Special warnings and precautions for use

Long term continuous topical therapy should be avoided where possible, particularly in infants and children, as adrenal suppression can occur readily even without occlusion.

If used in childhood, or on the face, courses should be limited to 5 days and occlusion should not be used. It should be noted that the child’s napkin may act as an occlusive dressing.

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 and severe eczema.

If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye, as glaucoma might result. If the ointment does enter the eye, the affected eye should be bathed in copious amounts of water.

Topical corticosteroids may be hazardous in psoriasis for a number of reasons, including rebound relapses, development of tolerance, risk of generalized 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.

Extension of the infection may occur due to the masking effect of the steroid.

If infection persists, systemic chemotherapy is required. Any spread of infection requires withdrawal of topical corticosteroid therapy.

Bacterial infection is encouraged by the warm, moist conditions induced by occlusive dressings, and the skin should be cleansed before a fresh dressing is applied.

Following significant systemic absorption, aminoglycosides such as neomycin can cause irreversible ototoxicity; and neomycin has nephrotoxic potential.

In renal impairment, the plasma clearance of neomycin is reduced (see Dosage in Renal Impairment).

Extended or recurrent application may increase the risk of contact sensitization. Products which contain antimicrobial agents should not be diluted.

4.5 Interaction with other medicinal products and other forms of interaction

Neomycin sulphate can intensify and prolong the respiratory depressant effects of neuromuscular blocking agents following systemic absorption. However, if used in accordance with the recommendations systemic exposure to neomycin sulphate is expected to be minimal and drug interactions are unlikely to be significant. No hazardous interactions have been reported with use of clobetasol propionate or nystatin.

4.6 Pregnancy and lactation

There is little information to demonstrate the possible effect of topically applied neomycin in pregnancy and lactation. However, neomycin present in maternal blood can cross the placenta and may give rise to a theoretical risk of foetal toxicity, thus the use of Clobetasol/neomycin/nystatin Ointment is not recommended in pregnancy and lactation.

The safe use of clobetasol propionate during lactation has not been established.

4.7 Effects on ability to drive and use machines

Clobetasol/neomycin/nystatin Ointment is not expected to have any effect.

4.8 Undesirable effects

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.

As with other topical corticosteroids prolonged use of large amounts 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 if occlusive dressings are used. Provided the weekly dosage is less than 50g in adults, any suppression of the HTA axis is likely to be transient with a rapid return to normal values once the short course of steroid therapy has ceased. The same applies to children given a proportionate dosage.

Prolonged and intensive treatment with highly active corticosteroid preparations may cause local atrophic changes in the skin such as thinning, striae, and dilatation of the superficial blood vessels, particularly when occlusive dressings are used, or when skin folds are involved.

In rare instances, treatment of psoriasis with corticosteroids (or its withdrawal) is thought to have provoked the pustular form of the disease (see Special Warnings and Precautions for Use).

There are reports of pigmentation changes and hypertrichosis with topical steroids.

Clobetasol/neomycin/nystatin Ointment is usually well tolerated, but if signs of hypersensitivity appear, application should be stopped immediately.

Exacerbation of symptoms may occur.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

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 reduced or discontinued gradually under medical supervision because of the risk of adrenal insufficiency.

Also, consideration should be given to significant systemic absorption of neomycin sulphate (see Special warnings and precautions for use). If this is suspected, use of the product should be stopped and the patient’s general status, hearing acuity, renal and neuromuscular functions should be monitored.

Blood levels of neomycin sulphate should also be determined. Haemodialysis may reduce the serum level of neomycin sulphate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Clobetasol propionate is a highly active corticosteroid with topical antiinflammatory activity. The major effect of clobetasol propionate on skin is a nonspecific anti-inflammatory response, partially due to vasoconstriction and decrease in collagen synthesis.

The use of nystatin in the local treatment of candidal infections of the skin and of neomycin as a broad spectrum antibiotic is well known.

The principle action of the preparation is based on the anti-inflammatory activity of the corticosteroid. The broad spectrum antibacterial and anti-candidal activity provided by the combination of neomycin and nystatin allow this effect to be utilized

in the treatment of conditions which are or are likely to become infected.

5.2 Pharmacokinetic properties

Percutaneous penetration of clobetasol propionate varies among individuals and can be increased by the use of occlusive dressings, or when the skin is inflamed or diseased.

Mean peak plasma clobetasol propionate concentrations of 0.63ng/ml occurred in one study 8 hours after the second application (13 hours after an initial application) of 30g clobetasol propionate 0.05% ointment to normal individuals with healthy skin. Following the application of a second dose of 30g of clobetasol propionate cream 0.05% mean peak plasma concentrations were slightly higher than the ointment and occurred 10 hours after application.

In a separate study, mean peak plasma concentrations of approximately 2.3ng/ml and 4.6ng/ml occurred respectively in patients with psoriasis and eczema 3 hours after a single application of 25g clobetasol propionate 0.05% ointment. However, systemic metabolism of clobetasol has never been fully characterised or quantified. Following percutaneous absorption of clobetasol propionate the drug probably follows the metabolic pathway of systemically administered corticosteroids, i.e. metabolised primarily by the liver and then excreted by the kidneys.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Titanium dioxide (E171)

Liquid paraffin

Soft white paraffin

6.2 Incompatibilities

None known.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store below 25°C.

6.5 Nature and contents of container

Collapsible aluminum tube, with a polypropylene cap. Pack sizes: 25g or 30g.

6.6 Special precautions for disposal

Do not dilute.

Patients should be advised to wash their hands after applying Clobetasol/neomycin/nystatin Ointment unless it is the hands that are being treated.

7 MARKETING AUTHORISATION HOLDER

Chemidex Pharma Limited T/A Essential Generics Chemidex House,

Unit 7, Egham Business Village,

Crabtree Road,

Egham, Surrey TW20 8RB United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 17736/0101

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19 November 1999

10 DATE OF REVISION OF THE TEXT

05/04/2016