Dermovate Scalp Application
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dermovate Scalp Application
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 1 g contains 0.5 mg of clobetasol propionate (0.05% w/w).
3. PHARMACEUTICAL FORM
Scalp application
4.1. Therapeutic Indications
Clobetasol propionate is a highly active topical corticosteroid which is indicated for use in short courses for conditions which do not respond satisfactorily to less active steroids.
Steroid responsive dermatoses of the scalp such as:
- Psoriasis.
- Recalcitrant dermatoses.
4.2. Posology and Method of Administration
Route of administration: Topical, on the scalp.
Owing to the flammable nature of the product, Dermovate Scalp Application should be kept away from open fire and flames and all sources of ignition, including smoking, during and immediately after use.
Adults, Elderly and Children over 1 year
A small quantity of clobetasol should be applied to the scalp night and morning until improvement is noticeable. It may then be possible to sustain improvement by applying once a day, or less frequently.
Paediatric population
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.
Care should be taken when using clobetasol propionate to ensure the amount applied is the minimum that provides therapeutic benefit.
Duration of treatment for children and infants
Courses should be limited if possible to a few days and reviewed weekly.
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. Contra-Indications
Infections of the scalp.
Hypersensitivity to the active substance or any of the excipients listed in section 6.1.
Dermatoses in children under one year of age, including dermatitis.
4.4. Special Warnings and Precautions for Use
Care must be taken to keep the preparation away from the eyes. Patients should be advised to avoid:
• smoking whilst applying to the scalp
• fire, flame and heat including use of hair dryer after application
Clobetasol should be used with caution in patients with a history of local hypersensitivity to other corticosteroids or to any of the excipients in the preparation. 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)
• Increasing hydration of the stratum corneum
• Use on thin skin areas
• 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
In infants and children under 12 years of age, long-term continuous topical corticosteroid therapy should be avoided where possible, as adrenal suppression can occur.
Children are more susceptible to develop atrophic changes with the use of topical corticosteroids.
Duration of treatment for children and infants
Courses should be limited if possible to a few days and reviewed weekly.
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.
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.
4.5 Interaction with other Medicaments and other forms of Interaction
Co-administered drugs that can inhibit CYP3A4 (eg ritonavir and 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
4.6. Fertility, pregnancy and lactation Pregnancy
There are limited data from the use of clobetasol 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. Administration of clobetasol 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.
Breast-feeding
The safe use of topical corticosteroids during lactation has not been established.
It is not known whether the topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Administration of clobetasol during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.
If used during lactation clobetasol 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
Clobetasol administered subcutaneously to rats had no effect upon mating performance; however, fertility was decreased at the highest dose (see section 5.3).
4.7 Effect on Ability to Drive and Use Machines
There have been no studies to investigate the effect of clobetasol 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 clobetasol.
4.8. 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
Uncommon Skin atrophy*, striae*, telangiectasias*
Very rare Skin thinning*, skin wrinkling*, skin dryness*, pigmentation
changes*, hypertrichosis, exacerbation of underlying symptoms, allergic contact dermatitis/dermatitis, pustular psoriasis, erythema, rash, urticaria
General Disorders and Administration Site Conditions
*Skin features secondary to local and/or systemic effects of hypothalamic-pituitary adrenal (HPA) axis suppression.
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
Symptoms and signs
Topically applied clobetasol 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, clobetasol 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
D07AD Corticosteroids, very potent (group IV)
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.
5.2 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.
Mean peak plasma clobetasol propionate concentrations of 0.63 ng/ml occurred in one study eight hours after the second application (13 hours after an initial application) of 30 g clobetasol propionate 0.05% ointment to normal individuals with healthy skin. Following the application of a second dose of 30 g 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 2.3 ng/ml and 4.6 ng/ml occurred respectively in patients with psoriasis and eczema three hours after a single application of 25 g clobetasol propionate 0.05% ointment.
Distribution
The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that 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.
5.3 Preclinical Safety Data
Carcinogenesis / Mutagenesis Carcinogenesis
Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
Genotoxicity
Clobetasol propionate was not mutagenic in a range of in vitro bacterial cell assays.
Reproductive Toxicology Fertility
In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on mating, and fertility was only decreased at 50 micrograms/kg/day.
Pregnancy
Subcutaneous administration of clobetaol propionate to mice (>100 micrograms/kg/day), rats (400 micrograms/kg/day) or rabbits (1 to 10 micrograms/kg/day) during pregnancy produced foetal abnormalities including cleft palate and intrauterine growth retardation.
In the rat study, where some animals were allowed to litter, developmental delay was observed in the F1 generation at >100 micrograms/kg/day and survival was reduced at 400 micrograms/kg/day. No treatment-related effects were observed in F1 reproductive performance or in the F2 generation.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Carbomer Isopropyl Alcohol Sodium Hydroxide Purified Water
6.2 Incompatibilities
None known.
6.3 Shelf life
24 months
6.4 Special precautions for storage
Do not store above 30°C.
Keep container tightly closed when not in use. Contents are flammable. Keep away from fire, flame or heat. Do not leave Dermovate Scalp Application in direct sunlight.
6.5 Nature and contents of container
White opaque low density polyethylene squeeze bottle with a polyethylene nozzle and either a polystyrene or high density polyethylene cap or
White High Density Polyethylene (HDPE) Hostalen GF4750 and Remafin white CEG 020 container with a polyethylene nozzle and either a polystyrene or polyethylene cap.
Pack size: 25ml, 30ml, 100ml.
6.6 Special precautions for disposal and other handling
Patients should be advised to wash their hands after applying Dermovate Scalp Application.
For detailed instructions for use refer to the Patient Information Leaflet in every pack.
Do not use near a naked flame.
7 MARKETING AUTHORISATION HOLDER
Glaxo Wellcome UK Ltd trading as
GlaxoSmithKline UK Stockley Park West Uxbridge Middlesex UB11 1BT
8. MARKETING AUTHORISATION NUMBER
PL 10949/0046
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
24/02/2010
10
DATE OF REVISION OF THE TEXT
04/11/2014