Summary of medicine characteristics - CLARELUX 500MICROGRAMS / G CUTANEOUS FOAM IN PRESSURISED CONTAINER
1 NAME OF THE MEDICINAL PRODUCT
CLARELUX 500 micrograms/g cutaneous foam in pressurised container
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One gram of cutaneous foam contains 500 micrograms of clobetasol propionate.
500 micrograms of clobetasol propionate are equivalent to 440 micrograms of clobetasol.
Excipient(s) with known effect
One gram of cutaneous foam contains 604.3 mg of ethanol, 20.9 mg of propylene glycol, 11.5 mg of cetyl alcohol and 5.2 mg of stearyl alcohol.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Cutaneous foam in pressurised container.
White foam that breaks down upon contact with skin.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
CLARELUX 500 micrograms/g, cutaneous foam in pressurised container is indicated for a short-course treatment of steroid responsive dermatoses of the scalp such as psoriasis, which do not respond satisfactorily to less active steroids.
4.2 Posology and method of administration
Clobetasol propionate belongs to the most potent class of topical corticosteroids (group IV) and prolonged use may result in serious undesirable effects (see section 4.4). If
treatment with a local corticosteroid is clinically justified beyond 2 weeks, a less potent corticosteroid preparation should be considered. Repeated but short courses of clobetasol propionate may be used to control exacerbations (see details below).
Posology
Use in adults
CLARELUX 500 micrograms/g, cutaneous foam in pressurised container is a highly potent topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks and amounts greater than 50 g/week should not be used.
Route of administration: for cutaneous use.
CLARELUX 500 micrograms/g, cutaneous foam in pressurised container should be applied to the affected area twice daily. There are no data from clinical studies evaluating the efficacy of once daily application.
Paediatric population
CLARELUX is not recommended for use in children less than 12 years old (see section 5.1).
Method of administration
For cutaneous use
The foam application has been designed so that the preparation spreads easily without being too fluid and allows easy application direct to the affected area.
Note: for proper dispensing of foam, hold the container upside down and depress the actuator.
Invert the container and dispense a small amount (of the size of a walnut or one teaspoon) of CLARELUX directly on the lesions, or dispense a small amount into the cap of the container, onto a saucer or other cool surface, taking care to avoid contact with eyes, nose, and mouth. Dispensing directly onto hands is not recommended, as the foam will begin to melt immediately upon contact with warm skin. Gently massage into affected area until the foam disappears and is absorbed. Repeat until entire affected area is treated. Move the hair away from the affected area so that the foam can be applied to each affected area.
Avoid contact with eyes, nose and mouth. Do not use near a naked flame.
4.3 Contraindications
CLARELUX is contraindicated in patients with:
hypersensitivity to clobetasol propionate, to other corticosteroids, or to any of the excipients listed in section 6.1;
ulcerated lesions, burns;
rosacea;
acne vulgaris;
perioral dermatitis;
perianal and genital pruritus.
The use of CLARELUX is contraindicated in the treatment of primary infected skin lesions caused by infection with parasites, viruses, fungi or bacteria.
CLARELUX 500 micrograms/g, cutaneous foam in pressurised container:
must not be used on the face
is contra-indicated in infants under 2 years old (see section 4.3)
must not be applied to the eyelids (risk of glaucoma and cataract).
4.4 Special warnings and precautions for use
Special warnings
Long term use
Cases of osteonecrosis, serious infections (including necrotizing fasciitis), and systemic immunosuppression (sometimes resulting in reversible Kaposi’s sarcoma lesions) have been reported with long-term use of clobetasol propionate beyond the recommended doses (see section 4.2). In some cases, patients used concomitantly other potent oral/topical corticosteroids or immunosuppressors (e.g. methotrexate, mycophenolate mofetil). If treatment with local corticosteroids is clinically justified beyond 2 weeks, a less potent corticosteroid preparation should be considered.
Hypersensitivity
CLARELUX should be used with caution in patients with a history of local hypersensitivity to 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.
Stop using immediately if signs of hypersensitivity appear.
Infections and infestations
The use of CLARELUX® on wounds or ulcerations is not recommended.
Secondary infection may develop; bacterial infection is encouraged by the warm, moist conditions induced by occlusive dressings, and so the skin should be cleansed before a fresh dressing is applied.
Any spread of infection requires withdrawal of topical corticosteroid therapy and administration of appropriate antimicrobial therapy.
Adrenal suppression
Manifestations of hypercortisolism (Cushing’s syndrome) and reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to glucocorticosteroid insufficiency, can occur in some individuals, particularly in children 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).
Long-term continuous topical therapy should be avoided as adrenal suppression can occur readily even without use with an occlusive dressing. Upon clearing of lesions or after a maximum treatment period of two weeks, change to intermittent therapy or consider replacing with a weaker steroid.
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 (see Precautions for use) or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Precautions for use
Increased systemic absorption of topical steroids
Increased systemic absorption of topical steroids can lead to occurrence of systemic adverse reactions (i.e., adrenal suppression, immunosuppression). Increased systemic absorption of topical steroids can be facilitated by:
– long term exposure,
– application to a large surface area,
– use on occluded skin areas (e.g. on intertriginous areas or under occlusive dressings),
– use on thin areas (e.g. face),
– use on broken skin or other conditions where the skin barrier may be impaired,
– and increasing hydration of the stratum corneum.
Unless supervised by a physician, CLARELUX should not be used with occlusive dressings.
Rebound phenomenon
A rebound phenomenon in the form of flushing, stinging and burning of the skin may be seen in the event of sudden discontinuation after long-term use. This can be avoided by withdrawing treatment gradually.
Topical corticosteroids may be hazardous because rebound relapses can follow development of tolerance. Patients may also be exposed to the risk of developing generalised pustular psoriasis and local or systemic toxicity due to impaired barrier function of the skin. Careful patient supervision is important.
Eye disorders
Systemic corticosteroids therapy is associated with glaucoma and cataract formation. This risk has also been reported during ophthalmic treatment, and during regular local corticosteroid application to the eyelids. Additionally there have been reports of cataracts and glaucoma in patients following prolonged potent topical corticosteroid overuse on the face and/or the body. Although hypertensive effect of topical steroid is usually reversible after cessation of treatment, the visual defects resulting from glaucoma and cataracts are irreversible.
CLARELUX should not be applied on the eyelids.
Patients should wash their hands after each application to avoid eye contamination with CLARELUX. If CLARELUX becomes in contact with the eye, the affected eye should be bathed in copious amounts of water.
Patients on prolonged courses of potent topical steroids should be screened for cataract and glaucoma on a regular basis, especially patients with known risk factors for cataract (e.g. diabetes, smokers) or for glaucoma (e.g. personal or family history of glaucoma).
Paediatric population
CLARELUX is not recommended for use in children less than 12 years old (see section 5.1).
Excipients with known effect
This medicinal product contains:
□ 2145 mg of ethanol in each application, which may cause burning sensation on
damaged skin,
– 74 mg of propylene glycol in each application,
– cetyl alcohol and stearyl alcohol, which may cause local skin reactions (e.g. contact dermatitis).
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Fertility, pregnancy and lactation
Pregnancy
Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development (see 5.3). There are no adequate and well-controlled studies of clobetasol propionate in pregnant women. Epidemiological studies in pregnant women following use of oral corticosteroids have indicated little or no risk with regard to an association with cleft palate.
CLARELUX should not be used during pregnancy unless clearly necessary.
Breastfeeding
The safe use of clobetasol propionate during lactation has not been established.
Glucocorticosteroids are excreted in breast milk, therefore CLARELUX should not be used in breast-feeding women unless clearly necessary.
Fertility
No animal studies were conducted to evaluate the effect of clobetasol on male or female fertility.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
Summary of the safety profile
As with other topical corticosteroids, prolonged use of large amounts, or treatment of extensive areas can result in adrenocortical suppression. This is likely to be transient if the weekly dosage does not exceed 50g in adults.
Prolonged and intensive treatment with a highly active corticosteroid preparation may cause local changes in the skin such as skin atrophy, ecchymoses secondary to skin atrophy, skin fragility, telangiectasia, especially on the face, striae particularly affecting the proximal limbs.
Additional local adverse events associated with glucorticosteroids include perioral dermatitis, rosacea-like dermatitis, delayed wound healing, rebound phenomenon which can lead to dependence on corticosteroids, and effects on the eyes. Rise of intraocular pressure and increased risk for cataract are known side effects for glucocorticosteroids (see section 4.4).
In rare instances, treatment of psoriasis with corticosteroids (or its withdrawal) is thought to have provoked the pustular form of the disease (see section 4.4).
Secondary infection may develop; bacterial infection is encouraged by the warm, moist conditions induced by occlusive dressings, and so the skin should be cleansed before a fresh dressing is applied. If the product is not used properly, bacterial, viral, parasitic, and fungal infections may be masked and/or aggravated (see section 4.4). Folliculitis has also been reported.
Contact allergy to CLARELUX or one of the excipients may occur. If signs of hypersensitivity appear, applications should be stopped immediately. Exacerbation of symptoms may occur.
The most commonly observed adverse reactions associated with the use of clobetasol propionate cutaneous foam formulations in clinical trials were application site reactions including burning (5%) and other non-specified reactions (2%).
Tabulated list of adverse reactions
The adverse reactions are classified by System Organ Class and frequency, using the following convention: Very common (> 1/10), Common (> 1/100 to < 1/10), Uncommon (> 1/1,000 to < 1/100), Rare (> 1/10,000 to < 1/1,000), Very rare (<1/10,000), not known (cannot be estimated from the available data)”.
| SOC | Common | Very rare | Unknown |
| Infections and infestations | Secondary infections Folliculitis | ||
| Endocrine disorders | Pituitary adrenal system suppression | ||
| Nervous system disorders | Paraesthesia | ||
| Eye disorders | Eye irritation | Cataract Blurred vision | |
| Skin and subcutaneous tissue disorders | Vasodilatation Dermatitis NOS Contact dermatitis Psoriasis aggravated Skin irritation Skin tenderness Skin tightness | Pigmentation change Hypertrichosis | |
| General disorders and administration site conditions | Application site burning Application site reaction NOS | Application site erythema Application site pruritus Pain NOS | |
| Investigations | Blood urine present Mean cell volume increased Protein urine present Urine nitrogen |
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; Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
4.9 OverdoseNo overdoses have been reported. Topically applied CLARELUX in pressurised container can be absorbed in sufficient amounts to produce systemic effects. If features of hypercorticoidism appear topical steroids should be discontinued gradually and, because of the risk of acute adrenal suppression, this should be done under medical supervision (see section 4.4).
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteroids, very potent (group IV)
ATC code: D07A D01
Mechanism of action
Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
Pharmacodynamic effects
A vasoconstrictor study has shown that CLARELUX has a comparable potency, based upon skin blanching response, as other clobetasol propionate formulations.
Clinical efficacy and safety
The efficacy and safety of clobetasol propionate (CP) foam 0.05% has been demonstrated in a double-blind placebo and active comparator (CP solution) controlled study: 188 adult participants were treated for moderate to severe psoriasis of the scalp during 2 weeks. Products were applied twice a day over the entire scalp area. Pruritus, scaling, erythema and plaque thickness were evaluated after 2 weeks of treatment. 74% of participants using CP foam were rated completely clear or almost clear compared 6–10% of the placebo group and 61% of the CP solution group. All disease signs and symptoms were significantly improved after 2 weeks and also following 2 weeks off treatment.
Clinical data in children and adolescents established that Clobetasol foam is safe and effective for treatment of mild-to-moderate plaque-type psoriasis in patients aged 12 years or older. A double-blind randomised placebo vehicle-controlled trial was performed in 497 patients aged 12 years or older. (253 were given clobetasol EF foam, 123 received vehicle foam, and 121 received clobetasol ointment, each for two weeks). About 27% of the participants were adolescents. Compared with the vehicle foam, clobetasol foam was almost 4 times more effective in treating mild-to-moderate plaque-type psoriasis in the total population (47% vs 12%). Efficacy was similar between adolescents and adults and the incidence of AEs was comparable between clobetasol foam and vehicle foam for adults and paediatric participants as young as 12 years.
5.2 Pharmacokinetic properties
Absorption and distribution
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the carrier, the integrity of the epidermal barrier, the severity of the disease and the area treated. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
Topical corticosteroids can be absorbed from intact healthy skin.
Metabolism and elimination
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
In a controlled pharmacokinetic study, 3 of 13 subjects experienced reversible suppression of the adrenals at any time during the 14 days of CLARELUX therapy to at least 20% of the body surface area.
5.3 Preclinical safety data
5.3 Preclinical safety dataNon-clinical data reveal no special hazard for humans based on studies of repeated dose toxicity and genotoxicity. No topical studies were performed to assess the safety, pharmacology and the carcinogenic potential of clobetasol.
Parenteral administration of corticosteroids, including clobetasol propionate, to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. Animal studies have indicated that intrauterine exposure to corticosteroids may contribute to the development of cardiovascular and metabolic diseases in adult life, but there is a lack of evidence for the occurrence of such effects in humans (see section 4.6).
In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on male fertility. In females, increased embryofetal loss and growth suppression and thymic atrophy in the litters were observed at the highest dose.
6.1 List of excipients
Ethanol anhydrous
Purified water
Propylene glycol
Cetyl alcohol
Stearyl alcohol
Polysorbate 60
Citric acid anhydrous
Potassium citrate
Propellant: propane/n-butane/isobutane
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate. Store upright.
The canister contains a pressurised, flammable liquid. Do not use near a naked flame. Do not expose to temperatures higher than 50°C or to direct sunlight. Do not pierce or burn the canister, even when empty.
6.5 Nature and contents of container
6.5 Nature and contents of containerPressurised aluminium container closed with an inverted valve, containing 50g or 100g of foam. The inside of the can is lined with a double coated, clear epoxyphenolic lacquer. Each filled canister is fitted into a spout actuator with dust cap.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Pierre Fabre Limited
250 Longwater Avenue
Green Park
Reading
RG2 6GP
8 MARKETING AUTHORISATION NUMBER(S)
PL 00603/0248
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
29/03/2012