Dermovate

INSTRUCTIONS for medical use of the medicinal product DERMOWAIT (DERMOVATE)

Composition:

active substance: clobetasol propionate;

1 g of ointment contains 0.5 mg of clobetasol propionate;

excipients: propylene glycol, white soft paraffin, and sorbitan sesquioleate.

Pharmaceutical form. Ointment.

Main physicochemical properties: a homogeneous white semi-transparent ointment, free from undispersed particles and foreign inclusions.

Pharmacotherapeutic group. Corticosteroids for topical use. High-potency 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.

The penetration of clobetasol propionate through the skin varies among individuals and may increase with the use of occlusive dressings or in the presence of inflamed or damaged skin. In individuals with healthy skin, the mean peak plasma concentration of clobetasol propionate was 0.63 ng/mL in one study, observed 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, the mean peak plasma concentration was slightly higher than with the ointment and was observed at 10 hours. In another study, mean peak concentrations (approximately 2.3 ng/mL and 4.6 ng/mL) were observed in patients with psoriasis and eczema, respectively, 3 hours after a single application of 25 g of 0.05% clobetasol propionate ointment. After absorption through the skin, the drug most likely follows the same metabolic 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 use in adults, elderly patients, and children aged 1 year and older, for the short-term treatment of relatively more resistant inflammatory and pruritic manifestations of steroid-responsive dermatoses that are unresponsive to less potent corticosteroids.

Such conditions include:

• psoriasis (excluding 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 itching.

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 increasing 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 with 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 agent.

The drug should be used with caution in patients with a history of local hypersensitivity reactions to corticosteroids or any of the excipients. Local hypersensitivity reactions (see section "Side effects") 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 gland suppression in some individuals may result from increased systemic absorption of topical steroids. If any of the above symptoms occur, the drug should be gradually discontinued by reducing the frequency of application or switching to a less potent corticosteroid. Abrupt discontinuation of treatment may lead to glucocorticoid insufficiency (see section "Side effects").

Risk factors for systemic effects include:

• Potency and formulation of the topical steroid;
• Duration of use;
• Application over a large skin surface area;
• Use on skin surfaces in contact (e.g., in intertriginous areas) 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 areas of damaged skin or other conditions involving impaired skin barrier function;
• Children may absorb a proportionally greater amount of topical corticosteroid compared to adults and are therefore more susceptible to systemic side effects. This is due to children having an underdeveloped skin barrier and a larger skin surface area relative to body mass 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 have a higher risk of developing adrenal suppression.

Children are more susceptible to developing atrophic changes with topical corticosteroid use. Treatment of children with Dermovate should last no more than 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 conditions, particularly under occlusive dressings. Therefore, the skin should be thoroughly cleaned before each application of an 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

Appropriate antibacterial agents should always be prescribed when treating inflammatory skin lesions with secondary infection. If infection spreads, topical corticosteroids should be discontinued and appropriate antibacterial therapy 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 frequency of local hypersensitivity reactions and a higher risk of local infections.

Application to the face

Application of the ointment to facial skin is not recommended, as this area is more prone to atrophic changes. If necessary, use should be limited to 5 days.

Application to the eyelids

When applying the ointment 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 have been observed 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 for evaluation of possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after use of systemic and topical corticosteroids.

Dermovate ointment contains 475 mg of propylene glycol per 1 g of product. Propylene glycol may cause skin irritation.

Dermovate ointment 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 clothing and bed linen reduces accumulation of the product in fabric but does not completely eliminate 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 in the fetus. 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 smallest effective amount should be used for the shortest possible duration.

Breastfeeding

The safety of clobetasol propionate during breastfeeding has not been established. It is unknown whether topical corticosteroids can be absorbed systemically to an extent that measurable amounts 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 prescribed during breastfeeding, the ointment should not be applied to the breasts to avoid accidental oral exposure of the infant.

Ability to influence the speed of reactions when driving or operating machinery.

No studies have been conducted to evaluate this effect. Given the side effect profile, no influence 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 courses of clobetasol propionate therapy may be used to control exacerbations (see details below).

The ointment is particularly suitable for the treatment of skin lesions associated with dryness, lichenification, or scaling.

The ointment should be applied gently in a thin layer, covering all affected areas of the skin, 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 product should be replaced with a less potent corticosteroid. After each application, wait for the ointment to be fully absorbed before applying a moisturizer.

If the condition worsens or fails to improve within 2–4 weeks, the diagnosis and treatment should be re-evaluated.

Repeated short courses of Dermovate may be used to manage disease exacerbations. 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.

Once disease control is achieved, clobetasol should be gradually discontinued, and continued use of a moisturizer should be maintained as supportive therapy.

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

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

For topical use only.

Dermatoses that are difficult to treat. Patients with frequent disease exacerbations.

Once the acute phase of the disease has responded to continuous topical corticosteroid therapy, intermittent application (once daily, twice weekly, without occlusive dressing) should be considered. Such treatment has been shown to effectively reduce the frequency of exacerbations.

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

Children.

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

Overdose.

Symptoms.

With regular 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 withdrawn by reducing the frequency of ointment application or by switching to a less potent corticosteroid, due to the risk of glucocorticosteroid insufficiency.

Further management should be based on the patient's clinical condition or according to national guidelines for the treatment of poisoning (if available).

Adverse Reactions

The adverse reactions listed below are classified by organ systems and by frequency of occurrence: very common ≥ 1/10, common ≥ 1/100 and < 1/10, uncommon ≥ 1/1000 and < 1/100, rare ≥ 1/10000 and < 1/1000, very rare < 1/10000, including isolated cases.

Infections and infestations

Very rare: opportunistic infections.

Immune system

Very rare: hypersensitivity, generalized rash.

Endocrine system

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

Skin and subcutaneous tissue

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

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

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

*Skin disorders 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 ointment in an aluminum tube with a polypropylene cap, 1 tube per cardboard package.

Prescription category. Prescription only.

Manufacturer. Delpharm Poznan S.A., Poland.

Manufacturer's address.

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