DERMOVAL 0,05 % Cr T/15g

Cream.
Tube of 15 g.

For 100 g of cream :

Clobetasol propionate: 0,050 g

Excipients with known effect: propylene glycol (47,5 g for 100 g of cream), cetostearyl alcohol, chlorocresol.

• Limited and resistant plaques
  • of psoriasis, particularly in its palmo-plantar locations,
  • of discoid lupus erythematosus,
  • lichen.
• Hypertrophic scars
• Non-infected corticosteroid-sensitive lesions, having resisted a lower-category corticosteroid and limited in surface area.

Remark :

• After a generally brief initial treatment, the relay is possibly ensured by a lower-level corticosteroid.
• Each dermatosis must be treated with the most appropriate level corticosteroid, knowing that depending on the results, one may be led to substitute a product of stronger or weaker activity on all or part of the lesions.

The cream form is particularly intended for acute, weeping lesions.

Apply once or twice daily in a thin layer to the surface to be treated and work in with gentle massage, until the cream is fully absorbed. Wash hands after application.

An increase in the number of daily applications would risk worsening adverse effects without improving therapeutic effects.

Treatment of large areas requires monitoring of the number of tubes used.

It is advised to apply the product in spaced dabs, then spread it by massaging lightly until it is completely absorbed.

Certain dermatoses (psoriasis, atopic dermatitis...) make a gradual discontinuation of the topical corticosteroid desirable. It can be achieved by reducing the frequency of applications and/or by using a less potent or less concentrated corticosteroid.

In case of worsening or lack of improvement after 2 weeks, the treatment and diagnosis must be re-evaluated.

When an acute episode has been effectively treated with continuous topical corticosteroid therapy, intermittent treatment may be considered. In cases of chronic intermittent use, the function of the hypothalamic-pituitary-adrenal axis should be evaluated regularly.

Paediatric population

The use of clobetasol propionate at 0,05 % is not recommended in children under 12 years of age and, where applicable, must be subject to strict medical supervision (see section Warnings and precautions).

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition,
• untreated infections,
• ulcerated lesions,
• acne,
• rosacea,
• perioral dermatitis,
• infant.

Special warnings

Manifestations of hypercorticism (Cushing's syndrome) and reversible inhibition of the hypothalamic-pituitary-adrenal axis, leading to adrenocortical insufficiency, may occur in some subjects due to increased systemic absorption of topical corticosteroids. In either case, the medicine should be discontinued gradually by reducing the frequency of application, or by substituting a corticosteroid of lower potency. Abrupt cessation of treatment may lead to adrenal insufficiency (see Section Adverse effects).

Factors likely to increase systemic effects are as follows:

• Activity and formulation of the topical corticosteroid
• Duration of exposure
• Application over a large area
• Cutaneous application under occlusion (e.g., to intertriginous areas or under an occlusive dressing or under diapers
• Increased hydration of the stratum corneum of the skin
• Application on thin skin surfaces such as the face
• Application on skin lesions or other situations involving impaired skin barrier
• Compared with adults, children, particularly young children, may absorb proportionally larger amounts of topical corticosteroids and are therefore more exposed to systemic adverse effects (Cushingoid syndrome and growth retardation). This is because children have an immature skin barrier and a greater body surface area to weight ratio compared with adults. These effects disappear on cessation of treatment, but abrupt withdrawal may be followed by acute adrenal insufficiency.

Visual disorders

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

Precautions for use

Paediatric population

In children under 12 years of age, long-term topical corticosteroid therapy should be avoided as far as possible due to the risk of adrenocortical insufficiency.

Children are more exposed to the risks of skin atrophy with the use of topical corticosteroids. If the use of clobetasol propionate at 0,05 % proves necessary in children, it is strongly recommended that treatment be limited to a few days only and reassessed each week.

Risk of infection under occlusion

Bacterial infection is promoted by the heat and moisture present in skin folds or under an occlusive dressing or under diapers. When using an occlusive dressing, the skin should be cleaned before each change of dressing.

Use in psoriasis

Topical corticosteroids should be used with caution in psoriasis, as rebound effects, development of tolerance, a risk of generalised pustular psoriasis and local or systemic toxicity due to impaired skin barrier have been reported in some cases. Use in the treatment of psoriasis requires careful medical supervision.

Application on the face

Prolonged application to the face is not recommended, as this area is more prone to the risks of skin atrophy. Prolonged use on the face of very potent corticosteroids exposes to the occurrence of corticosteroid-induced and paradoxically corticosteroid-sensitive dermatitis with rebound after each cessation. A progressive, particularly difficult withdrawal is then necessary.

Application to the eyelids

Prolonged application to the eyelids is not recommended due to the risk of cataract and glaucoma. If applied to this area, care should be taken to ensure that the topical corticosteroid does not enter the eye.

Concomitant infection

An appropriate antimicrobial treatment should be used whenever the treated inflammatory lesions become infected. Spread of the infection requires discontinuation of local corticosteroid therapy and administration of appropriate antimicrobial treatment.

Osteonecrosis, serious infections and immunosuppression

Cases of osteonecrosis, serious infections (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 concomitantly used other potent oral/topical corticosteroids or immunosuppressants (for example, methotrexate, mycophenolate mofetil). If local corticosteroid treatment is clinically justified beyond 2 weeks, a less potent corticosteroid preparation should be considered.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat dermatitis surrounding chronic leg ulcers. This use may be associated with an increase in local hypersensitivity reactions and the risk of local infection.

Risk of flammability

DERMOVAL 0,05 % cream contains paraffin. Inform your patients not to smoke or approach naked flames due to the risk of serious burns. Fabrics (clothing, bedding, dressings, etc.) that have been in contact with this product burn more easily and may pose a fire risk. Washing clothing and bedding may reduce product accumulation, but cannot eliminate it completely.

Other

If local intolerance appears, treatment must be discontinued and the cause must be investigated.

Avoid any contact with the eyes and mucous membranes.

This medicine contains 47,5 g of propylene glycol per 100 g of cream. Propylene glycol may cause skin irritation.

This medicine contains chlorocresol and may cause allergic reactions.

This medicine contains cetostearyl alcohol and may cause local skin reactions (for example: eczema).

Metabolic disorders such as decreased glucose tolerance have been observed with concomitant use of topical corticosteroids and antidiabetic agents. Advise the patient and reinforce blood glucose and urine self-monitoring, especially at the start of treatment.

Pregnancy

Animal studies conducted with systemic administration have shown a teratogenic effect. However, a large number of pregnancies (more than 1 000 pregnancies) exposed systemically to corticosteroids have shown no malformative or toxic effect of clobetasol propionate on the fetus or newborn. Therefore, the use of clobetasol propionate at 0,05 % may be considered during pregnancy if necessary.

Breast-feeding

Corticosteroids pass into breast milk after systemic administration. By the topical route, transdermal passage and therefore the risk of excretion of the corticosteroid into milk will depend on the surface area treated, the degree of epidermal alteration and the duration of treatment.

Therefore, given topical use, application of clobetasol propionate at 0,05 % is possible during breastfeeding.

Prolonged contact of the infant with the treated skin area of the mother should be avoided.

In case of application to the breasts, the skin should be cleansed before each feed in order to avoid accidental ingestion by the infant.

Fertility

There are no human data available to assess the effect of topical corticosteroids on fertility. Subcutaneous administration of clobetasol propionate in rats had no effect on mating; however, fertility decreased at the highest dose (see section Preclinical safety).

The effects on the ability to drive vehicles and use machines have not been studied.

An adverse effect on these activities cannot be anticipated based on the adverse effect profile of topical clobetasol propionate.

Adverse effects are listed below according to the MedDRA system organ classification and by frequency. The frequencies are as follows: 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) and not known (cannot be estimated from the available data).

Infections and infestations

Frequency not known : infections

Immune system disorders

Frequency not known : local hypersensitivity

Endocrine disorders

Frequency not known Adrenal insufficiency on abrupt withdrawal of treatment due to suppression of the hypothalamic-pituitary-adrenal axis.

Cushingoid syndrome (which notably manifests as a moon face and central obesity), and whose skin disorders are: skin atrophy, skin thinning, dry skin, striae, telangiectasia.

Skin and subcutaneous tissue disorders

Frequency not known : pruritus, local skin burning, changes in pigmentation, hypertrichosis, allergic contact dermatitis/dermatitis, pustular psoriasis, erythema, skin eruptions, urticaria, acne.

Prolonged use of very strong dermocorticoids may lead to ecchymotic purpura secondary to skin atrophy, as well as skin fragility.

When applied to the face, dermocorticoids may cause perioral dermatitis or worsen rosacea (see sections Contraindications and Warnings and precautions)

Folliculitis and worsening of rosacea have been reported.

A delay in healing of atonic wounds, bedsores, and leg ulcers may be observed (see section Contraindications).

General disorders and administration site conditions

Frequency not known : Irritation at the application site

Eye disorders

Frequency not known : Blurred vision, central serous chorioretinopathy (see section Warnings and precautions)

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

Signs and symptoms

Absorption of locally applied clobetasol propionate may be sufficient to cause systemic effects. Acute overdose is unlikely but, in cases of chronic overdose or misuse, symptoms of hypercorticism may appear (see section Adverse effects).

Treatment

In case of overdose, clobetasol propionate should be discontinued gradually by reducing application frequency or by substituting a dermocorticoid of lower potency, due to the risk of adrenal insufficiency.

Pharmacotherapeutic class: Very strong corticosteroid (group IV), ATC code: D07AD01

Topical corticosteroids are classified into 4 levels of activity according to skin vasoconstriction tests: very strong, strong, moderate, weak activity.

Clobetasol propionate, the active substance of DERMOVAL 0,05 % cream, is of very strong potency.

Active on certain inflammatory processes (for example: contact hypersensitivity) and the associated pruritic effect. Vasoconstrictor. Inhibits cell proliferation.

Mechanism of action

Topical corticosteroids have anti-inflammatory properties based on multiple mechanisms; they inhibit the late phase of allergic reactions, notably reduce mast cell density, chemotaxis and eosinophil activation, reduce cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibit arachidonic acid metabolism.

Pharmacodynamic effects

Topical corticosteroids have anti-inflammatory, antipruritic and vasoconstrictive properties.

The extent of transdermal passage and systemic effects depends on the size of the treated area, the degree of epidermal alteration, and the duration of treatment.

These effects are all the more to be feared the longer the treatment is prolonged.

Absorption

Topical corticosteroids may be absorbed through healthy skin and pass into the general circulation. The extent of percutaneous absorption of topical corticosteroids depends on various factors, such as the vehicle and the integrity of the epidermal barrier.

Application under occlusion, inflammation and/or other pathological skin processes may also increase percutaneous absorption.

Certain factors are likely to increase systemic effects (see section Warnings and precautions).

In 8 healthy volunteers, after 2 applications of 30 g of clobetasol propionate 0,05 %, ointment, the mean peak plasma concentration was 0,63 ng/mL. This mean peak plasma concentration obtained after application of clobetasol propionate 0,05 %, ointment, was slightly lower than that obtained after application of clobetasol propionate 0,05 %, cream.

Three hours after application of 25 g of clobetasol propionate 0,05 %, ointment in 9 patients with atopic dermatitis or psoriasis, the peak plasma concentration was between 0,6 and 15,8 ng/mL.

Biotransformation

Once absorbed through the skin, topical corticosteroids follow the same pharmacokinetic pathways as corticosteroids administered systemically. They are metabolised mainly by the liver.

Elimination

Topical corticosteroids are excreted by the kidneys.

No long-term animal study has been performed to evaluate the carcinogenic potential of clobetasol propionate, its genotoxic potential, or the effect of clobetasol propionate on fertility.

Subcutaneous administration of clobetasol propionate to mice and rats at doses ≥ 0,1 mg/kg/day, and to rabbits at doses of 1 to 10 μg/kg/day during gestation resulted in fetal abnormalities, including cleft palate and intrauterine growth retardation.

In a study in rats, in which some animals were allowed to reproduce, a developmental delay was observed for the F1 generation at a dose ≥ 0,1 mg/kg/day and a decreased survival rate at the dose of 0,4 mg/kg/day. No treatment-related effect was observed on reproductive capacity for the F1 generation or for the following generation (F2).

2 years.

Store at a temperature not exceeding 30 °C.

No special requirements.