Clobeskin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT KLOBESKIN (CLOBESKINE)

Composition:

Active substance: clobetasol;

1 g of the preparation contains micronized clobetasol propionate 0.5 mg;

Excipients: propylene glycol, sorbitan sesquioleate, white soft paraffin.

Pharmaceutical form. Ointment.

Main physicochemical properties: white ointment of uniform consistency.

Pharmacotherapeutic group. Corticosteroids for dermatological use. Highly potent corticosteroids (Group IV). Clobetasol. ATC code D07AD01.

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 with the use of occlusive dressings or in the presence of inflamed or damaged skin. 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 administration of a second dose of 30 g of 0.05% clobetasol propionate cream, mean peak plasma concentrations were slightly higher than with the ointment and were 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 following systemic administration. 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, and children aged 1 year and older, for relatively 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 itching, perioral dermatitis. The product is not intended for 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 systemic effects. The clinical significance of such interaction depends on the dose of the corticosteroid, the route of administration, and the potency of the CYP3A4 inhibitor.

Special precautions for use

The drug should be used with caution in patients with a history of local hypersensitivity reactions to corticosteroids or any excipients of the drug. Local hypersensitivity reactions (see section "Adverse reactions") may resemble the 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 patients may result from increased systemic absorption of topical corticosteroids. 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 "Adverse 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, 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 with impaired skin barrier function.

Compared to adults, children may absorb a proportionally greater amount of topical corticosteroid and are therefore 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 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 when using topical corticosteroids. Treatment of children with this drug should, if possible, not exceed 5 days. The need for continued treatment should be reviewed weekly. The drug should not be used under occlusive dressings in children.

Infection risk with occlusive dressings. The risk of bacterial infections increases in warm and moist conditions, which may develop under occlusive dressings. Therefore, the skin should be thoroughly cleaned each time before applying a new 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 using this drug for psoriasis treatment, the patient should be under close medical supervision.

Concomitant infections. Appropriate antibacterial agents should always be prescribed when treating infected inflammatory lesions. 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 incidence of local hypersensitivity reactions and a higher risk of local infections.

Application to the face. Applying ointment to facial skin is undesirable, as this area is more vulnerable to atrophic changes. If application to facial skin is necessary, the duration of use should be limited to 5 days.

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

The medicinal product contains propylene glycol, which may cause skin irritation.

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 after use of systemic and topical corticosteroids.

Cases of serious necrotizing infections (including necrotizing fasciitis) and systemic immunosuppression (sometimes leading to reversible Kaposi's sarcoma lesions) have been reported with prolonged use of clobetasol propionate exceeding recommended doses (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 is clinically justified for longer than 4 weeks, consideration should be given to switching to a less potent corticosteroid.

Healthcare providers should be aware that if this drug comes into contact with bandages, clothing, or bed linens, the fabric may become highly flammable. Patients should be warned of this risk and advised to avoid open flames while using the drug.

Use during pregnancy or breastfeeding.

Topical use of corticosteroids in pregnant animals has been shown to cause developmental abnormalities. Relevance of these findings to humans has not been established. The drug should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. The minimum effective amount should be used for the shortest possible duration.

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 amounts of the drug appear in breast milk. The drug 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 ointment should not be applied to the breasts to avoid accidental oral exposure of the infant.

Ability to affect reaction speed when driving or operating machinery.

No studies on this effect have been conducted. 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 topical corticosteroids remains clinically justified after 4 weeks, a less potent corticosteroid should be considered. Repeated but short courses of clobetasol propionate 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 occurs (with adequate response to treatment, improvement is usually seen within a few days). Thereafter, the frequency of application should be reduced, or the medication should be switched to a less potent corticosteroid. After each application, wait for a certain period to allow complete absorption of the ointment before applying an emollient.

If there is no improvement or worsening of symptoms within 2–4 weeks, the diagnosis and treatment should be re-evaluated.

Repeated short courses of treatment may be used to manage exacerbations. Treatment should not last longer than 4 weeks. If continuous long-term therapy is required, less potent corticosteroids 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 an emollient should be maintained as supportive therapy.

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

In cases of more resistant lesions, especially those associated with hyperkeratosis, the effect of the medication may be enhanced, if necessary, by covering the affected skin area with an occlusive polyethylene dressing. Usually, application of the occlusive film overnight is sufficient to achieve satisfactory results. The improvement achieved is typically maintained by applying the ointment without an occlusive dressing.

For topical use.

Chronic dermatoses that are difficult to treat. Patients with frequent exacerbations. 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 exacerbations.

The medication should continue to be applied to all previously affected skin areas or known sites of potential flare-ups. This treatment regimen should be combined with daily, continuous use of emollients. The patient's clinical condition, as well as the benefits and risks of continued therapy, 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 regular use, clobetasol 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, the medication should be gradually discontinued by reducing the frequency of ointment application or by switching to a less potent corticosteroid, due to the risk of glucocorticoid insufficiency.

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

Adverse reactions.

Infections and infestations: Opportunistic infections.

Immune system disorders: Local hypersensitivity.

Endocrine system disorders: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis: Cushingoid signs (e.g., moon face, central obesity), delayed increase in body weight/growth in children, osteoporosis, glaucoma, hyperglycemia/glucosuria, cataract, arterial hypertension, increased body weight/fat accumulation, decreased endogenous cortisol levels, alopecia, brittle hair.

Skin and subcutaneous tissue disorders: Itching, local sensation of burning/pain in the skin, local skin atrophy*, skin atrophic striae*, telangiectasia*, skin thinning*, skin wrinkling*, skin dryness*, pigmentary changes*, hypertrichosis, exacerbation of underlying symptoms, allergic contact dermatitis/dermatitis, pustular form of psoriasis, erythema, rash, urticaria, acne.

General disorders and administration site conditions: Irritation/pain at the application site.

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

Eye disorders: Visual blurring.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 25 g in a tube in a carton.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business.

Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.

(all stages of manufacturing, quality control, batch release)

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka Street, building 100, letter B-II (corpus 4).

(all stages of manufacturing, batch release)