CLOBEX 500 µg/g Shampooing Fl/125ml

Clobetasol propionate.......................................................................................................500 micrograms

For 1 g of shampoo

Excipient with known effect:

One gram of shampoo contains 100 milligrams of ethanol.

Topical treatment of moderate scalp psoriasis in adults.

Clobetasol propionate belongs to the class of more potent topical corticosteroids (group IV) and prolonged use may cause serious adverse effects (see section Warnings and precautions). If treatment with a topical corticosteroid is clinically justified beyond 4 weeks, a less potent corticosteroid preparation should be considered. Repeated short-term courses of clobetasol propionate may be used to control exacerbations (see details below).

Dosage

CLOBEX should be applied once daily directly to the dry scalp, taking care to thoroughly cover and massage the lesions. An amount equivalent to about one ½ tablespoon (about 7,5 ml) per application is sufficient to cover the entire scalp.

The total dose must not exceed 50 g per week.

Method of administration

For cutaneous use on the scalp only.

After application, CLOBEX should remain on without being covered for 15 minutes. Wash hands thoroughly after application. After 15 minutes, the product should be rinsed thoroughly with water and/or the hair may be washed, adding if necessary an additional amount of normal shampoo to facilitate cleansing. Then the hair may be dried as usual.

The duration of treatment should not exceed 4 weeks. Once the expected clinical result is obtained, applications will be spaced out or replaced if needed by another treatment. If there is no visible improvement after 4 weeks, a re-evaluation of the diagnosis may be necessary.

Repeated treatments with CLOBEX may be used to treat psoriasis flares, provided the patient is under regular medical supervision.

Special populations

Elderly patients:

Safety and efficacy data for CLOBEX in geriatric patients aged 65 years and older have not been established.

Renal impairment:

CLOBEX has not been studied in patients with renal insufficiency.

Hepatic impairment:

Patients with severe hepatic dysfunction should be treated with particular caution and closely monitored for side effects.

Paediatric population :

Experience in children is limited. The use of CLOBEX is not recommended in children and adolescents under 18 years. Use is contraindicated in children under 2 years (see sections Contraindications and Warnings and precautions).

• hypersensitivity to the active substance or to any of the excipients listed in section Composition ;

• CLOBEX must not be applied to skin with an infection of bacterial, viral (chickenpox, herpes simplex, herpes zoster), fungal or parasitic origin, ulcerated wounds and specific skin diseases (cutaneous tuberculosis, skin diseases due to syphilis);

• CLOBEX must not be applied to the eyes and eyelids (risk of glaucoma, risk of cataract);

• children under 2 years.

Hypersensitivity to corticosteroids may be observed.

Therefore, clobetasol propionate is not recommended in patients with hypersensitivity to other corticosteroids.

Cases of serious infections, osteonecrosis (including necrotising fasciitis) and systemic immunosuppression (sometimes resulting in reversible lesions of Kaposi's sarcoma) have been reported with long-term use of clobetasol propionate at doses higher than those recommended (see section Dosage and administration). In some cases, patients concurrently used other high-potency oral/topical corticosteroids or immunosuppressants (for example, methotrexate, mycophenolate mofetil). If local corticosteroid treatment is clinically justified beyond 4 weeks, a lower-potency corticosteroid preparation should be considered.

Continuous long-term treatment with corticosteroids, use of an occlusive dressing, and treatment of large areas, especially in children, may promote absorption and lead to a higher risk of systemic effects. In such cases, medical monitoring should be reinforced and patients may be periodically evaluated for possible suppression of the hypothalamic-pituitary axis. Systemic absorption of topical corticosteroids induced by prolonged use, especially over large areas, has resulted in reversible adrenal suppression with the potential for glucocorticoid insufficiency, and manifestations of Cushing's syndrome in some patients. Such systemic effects resolve when treatment is stopped. However, abrupt interruption may lead to acute adrenal insufficiency, particularly in children.

A patient with severe diabetes mellitus must be treated with particular care and closely monitored for side effects.

Topical corticosteroids must be used with caution as the development of tolerance (tachyphylaxis) may occur as well as local toxicity, such as skin atrophy, infection and telangiectasia of the skin.

CLOBEX is intended solely for the treatment of scalp psoriasis and must not be used to treat other skin areas. In particular, CLOBEX is not recommended for use on the face, intertriginous areas (axillary and genito-anal regions) and other eroded skin surfaces, as this could increase the risk of adverse effects such as atrophic changes, telangiectasia, corticosteroid-induced dermatitis or secondary infection. The face, more than other body regions, may show atrophic changes after prolonged treatment with potent topical corticosteroids.

In rare cases, treatment of psoriasis with corticosteroids (or its withdrawal) may cause generalised pustular psoriasis with intensive and prolonged topical use.

Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.

There may be a risk of rebound effect after treatment or of relapse upon abrupt discontinuation of clobetasol propionate treatment. Medical monitoring should therefore continue in the post-treatment period.

If CLOBEX gets into the eye, the affected eye should be rinsed with plenty of water.

Patients should be advised to use CLOBEX for the minimum time necessary to achieve the desired results. If signs of local intolerance appear, application should be suspended until they disappear. If signs of hypersensitivity appear, application should be stopped immediately.

In order to avoid interaction with hair dyes, such as hair colourants, clobetasol propionate shampoo must be rinsed thoroughly.

Visual disorders

Visual disturbances may occur during systemic or topical corticosteroid therapy. In case of blurred vision or onset of any other visual symptom occurring during corticosteroid therapy, an ophthalmological examination is required to look especially for cataract, glaucoma or a rarer lesion such as central serous chorioretinopathy, described with systemic or topical administration of corticosteroids.

Paediatric population

In this age group, growth retardation may also be observed with systemic absorption of topical corticosteroids. CLOBEX must not be used in children and adolescents aged 2 to 18 years.

If CLOBEX is used in children and adolescents under 18 years, treatment should be reviewed weekly.

This medicine contains 100 mg of alcohol (ethanol) per gram, equivalent to 10% w/w.

This may cause a burning sensation on damaged skin.

No interaction studies have been performed.

Pregnancy

There is no sufficiently relevant data regarding the use of clobetasol propionate in pregnant women. Animal studies have demonstrated reproductive toxicity (see section Preclinical safety). The potential clinical risk is not known.

CLOBEX must not be used during pregnancy except when truly necessary.

Breast-feeding

Systemically administered corticosteroids pass into breast milk. No effects on children have been reported to date. Nevertheless, as there is insufficient data on the possible passage of topical clobetasol propionate into breast milk, as well as on the biological and clinical consequences, CLOBEX must not be prescribed to breastfeeding women except in cases of real necessity.

Fertility

No data available. See section Preclinical safety.

CLOBEX has no or negligible effect on the ability to drive vehicles and use machines.

Summary of the safety profile

During the clinical development of CLOBEX, out of a total of 558 patients treated with CLOBEX, the most frequently reported adverse reactions are skin burning sensations. Their incidence is approximately 2,8%. Most of these adverse reactions are considered mild to moderate and are related neither to race nor to gender. Clinical signs of skin irritation have infrequently been reported (0,2 %). No serious adverse events related to the product have been reported during clinical studies.

List of adverse effects

Adverse reactions are classified by System Organ Class and by frequency, using the following conventions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10 000 to < 1/1000), very rare (< 1/10 000), frequency not known (cannot be estimated from the available data), and have been reported for CLOBEX in clinical and post-marketing studies (see table 1).

Table 1 - Adverse effects

CLOBEX must be applied for only 15 minutes before being rinsed off, systemic absorption is rarely observed (see section Pharmacokinetics) and consequently the risk of suppression of the hypothalamic-pituitary axis is very low compared with potent corticosteroids that are not rinsed off. If suppression of the hypothalamic-pituitary axis occurs, it should be transient with a rapid return to normal values.

Cataract has been reported when corticosteroids have been applied to the eyes or eyelids.

Immunosuppression and opportunistic infections have been reported in rare cases with prolonged use of potent topical corticosteroids.

A growth delay may be observed in children in the event of systemic absorption of topical corticosteroids.

Although not observed with CLOBEX, prolonged and/or intensive treatment with a preparation containing potent corticosteroids may lead to striae, purpura and generalised pustular psoriasis.

Rebound effects may occur upon discontinuation of treatment.

When applied to the face, very potent corticosteroids may also cause perioral dermatitis or worsen rosacea.

Cases of pigmentation change, eruption of pustules and hypertrichosis have been reported with topical corticosteroids.

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr.

Acute overdose is very unlikely; however, in the event of chronic overdose or misuse, signs of hypercortisolism may appear, in which case treatment should be discontinued gradually. However, this gradual discontinuation should be carried out under medical supervision because of the risk of acute adrenal suppression.

Pharmacotherapeutic class: VERY STRONG CORTICOSTEROIDS (Group IV), ATC code: D07AD01

Mechanism of action

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, anti-pruritic and vasoconstrictive properties. In general, the mechanism of the anti-inflammatory activity of topical corticosteroids is not elucidated. However, corticosteroids would act by inducing phospholipase A inhibitory proteins2, termed 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.

Studies in vitro of skin penetration-release in human skin showed that only a small percentage (0,1%) of the applied dose of CLOBEX is found in the epidermis (stratum corneum included) after application for 15 minutes and rinsing. The very low local absorption of clobetasol propionate from CLOBEX, when applied according to the recommendations for clinical use (15 minutes before rinsing), resulted in negligible systemic exposure in animal and human studies.

Available clinical studies show that only 1 patient out of 126 has a quantifiable plasma concentration of clobetasol propionate (0,43 ng/ml).

Current pharmacokinetic data indicate that systemic effects due to clinical treatment with CLOBEX are highly unlikely given the low systemic exposure to clobetasol propionate after topical administration.

Non-clinical data from conventional safety pharmacology, single and repeated dose toxicology and genotoxicity studies revealed no particular risk for humans. The carcinogenicity of clobetasol has not been studied.

In rabbits, CLOBEX was found to be slightly irritating to the skin and eyes; no delayed hypersensitivity was observed on the skin of guinea pigs.

In congenital toxicity studies in rabbits and mice, clobetasol propionate was found to be teratogenic when administered subcutaneously at low doses. In an embryotoxicity study conducted in rats with topical clobetasol, fetal immaturity and skeletal and visceral malformations were observed at relatively low doses. In addition to malformations, studies in animals exposed to high systemic doses of glucocorticoids during pregnancy also showed other effects on litters, such as intrauterine growth retardation. The clinical relevance of the effects of clobetasol and other corticosteroids in animal developmental studies is unknown.

3 years.

After first opening, store for 6 months.

For storage conditions of the medicine after first opening, see section Shelf life.

Store in the original primary container in order to protect from light.

No special requirements.