Clobeskin

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

Composition:

Active substance: clobetasol;

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

Excipients: glycerol monostearate; white wax; cetostearyl alcohol; polyethylene glycol stearate; propylene glycol; citric acid monohydrate; sodium citrate; chlorocresol; purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: opaque cream of white or almost white color, of uniform consistency.

Pharmaco-therapeutic group. Corticosteroids for dermatological use. Highly potent corticosteroids (Group IV). ATC code D07AD01.

Pharmacological properties.

Pharmacodynamics.

The primary effect of clobetasol propionate on the skin is 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 inflammation or skin damage. 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 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 within 3 hours after a single application of 25 g of 0.05% clobetasol propionate ointment in patients with psoriasis and eczema, respectively. After absorption through the skin, the drug most likely undergoes 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 individuals, and children aged 1 year and older, for 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.
• The cream 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 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.

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 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 gland dysfunction 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 glucocorticosteroid insufficiency (see section "Side effects").

Risk factors for systemic effects include:

• Potency and formulation of the topical steroid;
• Duration of treatment;
• 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 under conditions involving impaired skin barrier function.

Compared to adults, children may absorb a proportionally greater amount of topical corticosteroid and are therefore more susceptible to systemic side effects. This is due to children's underdeveloped skin barrier and 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 treated with topical corticosteroids. Treatment of children with the cream should, if possible, not exceed 5 days. The need for continued treatment should be reviewed weekly. The drug must not be used under occlusive dressings in children.

Infection risk with occlusive dressings. The risk of bacterial infections increases in warm and moist conditions, 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. Appropriate antibacterial agents should always be prescribed when treating inflammatory lesions that are infected. If infection spreads, topical corticosteroids should be discontinued and appropriate antibacterial therapy initiated.

Chronic leg ulcers. Topical corticosteroids may occasionally be 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. Application of the cream to facial skin is undesirable, as this area is more vulnerable to atrophic changes. If necessary, use should be limited to 5 days.

Application to the 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.

Cases of severe osteonecrotic infections (including necrotizing fasciitis) and systemic immunosuppression (sometimes resulting in regression of Kaposi's sarcoma lesions) have been reported following 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.

Excipients. The medicinal product contains: cetostearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis); propylene glycol, which may cause skin irritation; and chlorocresol, which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of the drug in pregnant women are limited.

Topical application of corticosteroids to pregnant animals may cause disturbances in fetal development. The relevance of these findings to humans has not been established. Clobetasol may be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. The minimum amount necessary 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 systemically absorbed to an extent that results in measurable levels in breast milk. The cream 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 cream 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 have been conducted to evaluate such effects. 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 topical corticosteroids remains clinically justified beyond 4 weeks, consideration should be given to switching to a less potent corticosteroid. Repeated but short courses of clobetasol propionate may be used to control flare-ups (see details below).

The cream is particularly suitable for treating moist and weeping skin areas.

Apply the cream gently in a thin layer, covering all affected skin areas, once or twice daily until clinical improvement occurs, then gradually reduce the frequency of application or switch to a less potent corticosteroid. With adequate response to treatment, improvement is usually achieved within a few days. After each application, wait for a certain period to allow complete absorption of the cream before applying an emollient.

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

Repeated short courses of treatment may be used to manage 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, especially those with hyperkeratosis, the effect of the drug may be enhanced 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 an occlusive dressing.

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

Recurrence of previous dermatoses may occur with 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, consider switching to intermittent application (once daily, twice weekly, without occlusive dressing). This regimen has been shown to effectively reduce the frequency of flare-ups.

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

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

Overdose.

Symptoms. With normal use, the cream 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 drug should be gradually withdrawn by reducing the frequency of cream application or by replacing it with 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

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 ≥ 1/1,000 and < 1/100, rare ≥ 1/10,000 and < 1/1,000, very rare < 1/10,000, including isolated cases.

Infections and infestations

Very rare: opportunistic infections

Immune system disorders

Very rare: local hypersensitivity

Endocrine system disorders

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

Skin and subcutaneous tissue disorders

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

Uncommon: local skin atrophy*, striae atrophicae*, telangiectasia*

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

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

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 25 g in a tube in a carton.

Prescription category. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVYA".

Manufacturer's address and place of business.

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

(all manufacturing stages, quality control, batch release)

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

(all manufacturing stages, batch release)