Dermovate

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DERMOWAYT (DERMOVATE)

Composition:

Active substance: clobetasol propionate;

1 g of cream contains 0.5 mg clobetasol propionate;

Excipients: glycerol monostearate, Arlacel 165 (glycerol monostearate and polyethylene glycol (100) stearate), cetyl stearyl alcohol, chlorocresol, sodium citrate, citric acid monohydrate, beeswax substitute 6621, propylene glycol, purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: homogeneous white cream or white with a slight shade.

Pharmacotherapeutic group. Corticosteroids for topical use. Highly potent corticosteroids. ATC code D07A D01.

Pharmacological properties.

Pharmacodynamics.

The primary effect of clobetasol propionate on the skin is a non-specific anti-inflammatory action due to vasoconstriction and reduced collagen synthesis.

Pharmacokinetics.

Skin penetration of clobetasol propionate varies among individuals and may increase when occlusive dressings are used or when skin is inflamed or damaged. In individuals with healthy skin, mean peak plasma concentrations of clobetasol propionate of 0.63 ng/mL were observed in one study 8 hours after the second application (13 hours after the first application) of 30 g of 0.05% clobetasol propionate ointment. After application of a second dose of 30 g of 0.05% clobetasol propionate cream, mean peak plasma concentrations were slightly higher than with ointment and were observed at 10 hours. In another study, mean peak concentrations (approximately 2.3 ng/mL and 4.6 ng/mL, respectively) were observed in patients with psoriasis and eczema 3 hours after a single application of 25 g of 0.05% clobetasol propionate ointment. After absorption through the skin, the drug is likely metabolized via the same pathway as corticosteroids administered systemically. However, the systemic metabolism of clobetasol has not been fully characterized.

Clinical characteristics.

Indications.

Clobetasol is a highly potent topical corticosteroid indicated for short-term treatment in adults, elderly patients, and children over 1 year of age, for relatively more resistant inflammatory and pruritic manifestations of steroid-responsive dermatoses that are unresponsive to less potent corticosteroids.

Such conditions include:

• Psoriasis (except generalized plaque psoriasis)
• Dermatoses that are difficult to treat
• Lichen planus
• Discoid lupus erythematosus
• Other skin disorders unresponsive to less potent corticosteroids.

Contraindications.

Hypersensitivity to any component of the product.

Untreated skin infections.

Rosacea.

Common acne.

Pruritus without inflammation.

Perianal and genital pruritus.

Perioral dermatitis.

Dermovate is not intended for the treatment of dermatoses in children under 1 year of age, including diaper dermatitis and diaper rash.

Interaction with other medicinal products and other forms of interaction.

Concomitant use with agents that may inhibit CYP3A4 (e.g., ritonavir, itraconazole) has been shown to inhibit corticosteroid metabolism, potentially leading to increased systemic effects. The clinical significance of such an interaction depends on the dose of the corticosteroid, the route of administration, and the potency of the CYP3A4 inhibitor.

Special precautions for use.

Cases of serious osteonecrotic infections (including necrotizing fasciitis) and systemic immunosuppression (sometimes leading to reversible Kaposi's sarcoma lesions) have been reported following prolonged use of clobetasol propionate at doses exceeding those recommended (see section "Dosage and administration"). In some cases, patients were concurrently using other potent oral/topical corticosteroids or immunosuppressants (e.g., methotrexate, mycophenolate mofetil). If treatment with topical corticosteroids lasting more than 4 weeks is clinically justified, consideration should be given to using a less potent corticosteroid.

The product should be used with caution in patients with a history of local hypersensitivity to corticosteroids or any of the excipients. Local hypersensitivity reactions (see section "Adverse reactions") may mimic symptoms of the disease being treated.

Manifestations of hypercorticism (Cushing's syndrome) and reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis with adrenal insufficiency in some individuals may result from increased systemic absorption of topical steroids. If any of the above symptoms occur, treatment should be gradually discontinued by reducing the frequency of application or switching to a less potent corticosteroid. Abrupt discontinuation of therapy may lead to glucocorticoid insufficiency (see section "Adverse reactions").

Dermovate cream contains:

• 475 mg of propylene glycol per 1 g of product; propylene glycol may cause skin irritation;
• cetostearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis);
• chlorocresol, which may cause allergic reactions.

Risk factors for systemic effects include:

• potency and formulation of the topical corticosteroid;
• duration of treatment;
• application over a large skin surface area;
• use on skin folds or under occlusive dressings (in infants, diapers may act as occlusive dressings);
• increased hydration of the stratum corneum;
• application to areas with thin skin, such as the face;
• application to damaged skin or under other conditions involving impaired skin barrier function;
• relatively higher absorption of topical corticosteroids in children compared to adults, making them more susceptible to systemic adverse effects. This is due to children having an underdeveloped skin barrier and a larger skin surface area relative to body weight compared to adults.

Children

Prolonged use of topical corticosteroids in infants and children under 12 years of age should be avoided whenever possible, as they are at higher risk of developing adrenal suppression.

Children are more susceptible to developing atrophic changes when using topical corticosteroids.

Treatment of children with Dermovate should not exceed 5 days, if possible. The need for continued treatment should be reviewed weekly. Dermovate should not be used under occlusive dressings in children.

Risk of infection with occlusive dressings

The risk of bacterial infections increases in warm and moist environments, such as skin folds or under occlusive dressings. Therefore, the skin should be thoroughly cleaned each time before applying a new occlusive dressing.

Psoriasis treatment

Topical corticosteroids should be used with caution in the treatment of psoriasis, as in some cases, relapses, development of tolerance, risk of generalized pustular psoriasis, and symptoms of local or systemic toxicity due to impaired skin barrier function have been reported. When used for psoriasis treatment, the patient should be under close medical supervision.

Concomitant infections

When treating inflammatory skin lesions with infection, appropriate antibacterial therapy should always be prescribed. If infection spreads, topical corticosteroids should be discontinued and appropriate antibacterial treatment initiated.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat dermatitis occurring around chronic leg ulcers. However, such use is associated with an increased incidence of local hypersensitivity reactions and a higher risk of local infections.

Application of cream to the face

Application of the cream to facial skin is undesirable, as this area is more susceptible to atrophic changes. If necessary, use should be limited to 5 days.

Application to eyelids

When applying the cream to the eyelids, care should be taken to avoid contact with the eyes, as repeated exposure may lead to cataract and glaucoma.

Visual disturbances

Visual disturbances may occur with both systemic and topical use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported following the use of systemic and topical corticosteroids.

Dermovate cream contains paraffin. Patients should be warned not to smoke or be near open flames due to the risk of severe burns. If the product comes into contact with fabric (clothing, bed linen, dressings, etc.), the material may ignite easily and cause a serious fire. Washing clothes and bed linen reduces accumulation of the product in fabric but does not completely remove it.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of Dermovate in pregnant women are limited.

Topical administration of corticosteroids to pregnant animals has resulted in developmental abnormalities. The relevance of these findings to humans is unknown. Clobetasol may be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. The minimum effective amount for the shortest possible duration should be used.

Breastfeeding

The safety of clobetasol propionate during breastfeeding has not been established. It is unknown whether topical corticosteroids can be systemically absorbed to an extent that measurable levels of the drug appear in breast milk. Dermovate should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant. If treatment is necessary during breastfeeding, the cream should not be applied to the breasts to avoid accidental oral exposure of the infant.

Effect on ability to drive or operate machinery.

No studies have been conducted to assess this effect. Given the adverse reaction profile, no effect on reaction speed during driving or operating machinery is expected.

Method of Administration and Dosage.

Clobetasol propionate belongs to the class of the most potent topical corticosteroids (Group IV), and prolonged use may lead to serious adverse effects (see section "Special Warnings and Precautions for Use"). If treatment with a topical corticosteroid remains clinically justified after 4 weeks of use, consideration should be given to switching to a less potent corticosteroid. Repeated, but short-term, courses of clobetasol propionate therapy may be used to control flare-ups (see details below).

The cream is particularly suitable for the treatment of moist and weeping skin areas.

The cream should be gently applied in a thin layer, covering all affected skin areas, once or twice daily until clinical improvement is observed (with adequate response to treatment, improvement is usually achieved within a few days). Thereafter, the frequency of application should be reduced or the treatment should be switched to a less potent corticosteroid. After each application, wait for a certain period to allow complete absorption of the cream before applying an emollient. If the condition worsens or no improvement is observed within 2–4 weeks, the diagnosis and treatment should be re-evaluated.

Repeated short-term courses of Dermovate may be used to control flare-ups. Treatment should not last longer than 4 weeks. If long-term continuous therapy is required, less potent corticosteroid preparations should be used.

The maximum weekly dose should not exceed 50 g.

In cases of more resistant lesions, particularly those with hyperkeratosis, the effect of Dermovate may be enhanced, if necessary, by covering the affected skin area with an occlusive polyethylene dressing. Usually, applying the occlusive film only overnight is sufficient to achieve a satisfactory response. The improvement achieved is typically maintained by applying the cream without occlusive dressing.

Once disease control is achieved, clobetasol should be gradually withdrawn, and continued use of an emollient should be maintained as supportive therapy.

Recurrence of symptoms of previous dermatoses may occur following abrupt discontinuation of clobetasol.

For topical use only.

Dermatoses that are difficult to treat. Patients with frequent disease flare-ups.

Once the desired effect has been achieved during the acute phase of the disease with continuous topical corticosteroid therapy, intermittent application (once daily, twice weekly, without occlusive dressing) should be considered. This regimen has been shown to effectively reduce the frequency of flare-ups.

The medication should continue to be applied to all previously affected skin areas or to known sites of potential flare-up. This treatment regimen should be combined with daily regular use of emollients. The patient’s clinical condition, as well as the benefit and risk of continued treatment, should be regularly assessed.

Children.

The medication is contraindicated for the treatment of dermatoses, including dermatitis, in children under 1 year of age.

Overdose.

Symptoms.

With normal use, Dermovate may be absorbed in amounts sufficient to produce systemic effects. The likelihood of acute overdose is very low; however, with chronic overdose or improper use, signs of hypercortisolism may occur.

Treatment.

In case of overdose, Dermovate should be gradually discontinued by reducing the frequency of cream application or by replacing it with a less potent corticosteroid, due to the risk of glucocorticoid insufficiency.

Further treatment should be based on the patient’s clinical condition or according to national guidelines for the management of poisoning, if applicable.

Side effects

The adverse reactions listed below are classified by system organ class and frequency of occurrence: very common ≥ 1/10, common ≥ 1/100 and < 1/10, uncommon ≥ 1/1000 and < 1/100, rare ≥ 1/10,000 and < 1/1000, very rare < 1/10,000, including isolated cases.

Infections and infestations

Very rare: opportunistic infections.

Immune system

Very rare: local hypersensitivity.

Endocrine system

Very rare: suppression of the hypothalamic-pituitary-adrenal (HPA) axis: Cushingoid features (e.g., moon face, central obesity), suppression of weight gain/growth in children, osteoporosis, hyperglycemia/glycosuria, arterial hypertension, increased body weight/obesity, decreased levels of endogenous cortisol, alopecia, hair fragility.

Skin and subcutaneous tissue

Common: pruritus, sensation of local burning/pain in the skin.

Uncommon: local skin atrophy*, atrophic striae*, telangiectasia*.

Very rare: skin thinning*, skin wrinkling*, skin dryness*, pigmentary changes*, hypertrichosis, exacerbation of underlying symptoms, allergic contact dermatitis/dermatitis, pustular psoriasis, erythema, rash, urticaria, acne.

*Skin lesions secondary to local and/or systemic hypothalamic-pituitary-adrenal suppression.

General disorders and administration site conditions

Very rare: irritation/pain at the application site.

Eye disorders

Very rare: glaucoma, cataract.

Not known: visual blurring.

Shelf life.

2 years.

Storage conditions.

Store below 30 °C. Keep out of reach of children.

Packaging.
25 g of cream in an aluminum tube with a polypropylene cap, 1 tube per cardboard box.

Prescription category.
Prescription only.

Manufacturer.
Delpharm Poznan S.A., Poland.

Manufacturer's address.

189, Grunwaldzka Street, 60-322 Poznan, Poland.