DERILIFE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DERYLIFE (DERYLIFE)

Composition:

Active substance: clobetasol;

1 g of cream contains clobetasol propionate 0.5 mg;

Excipients: white wax; propylene glycol; chlorocresol; polyethylene glycol (macrogol) cetylstearyl ether; polyoxyl hydrogenated castor oil; polyethylene glycol (macrogol) hydroxystearate; cetylstearyl alcohol; purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: a homogeneous white or almost white cream.

Pharmacotherapeutic group. Topical corticosteroids. High-potency corticosteroids.

ATC code D07AD01.

Pharmacological Properties

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

Pharmacokinetics. Skin penetration of clobetasol 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 maximum plasma concentration (Cmax) of clobetasol 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 ointment. After administration of a second dose of 30 g of 0.05% clobetasol cream, the mean Cmax was slightly higher than with the ointment and was reached after 10 hours. In another study, mean Cmax (approximately 2.3 ng/mL and 4.6 ng/mL) was observed in patients with psoriasis and eczema, respectively, 3 hours after a single application of 25 g of 0.05% clobetasol ointment. Following absorption through the skin, clobetasol most likely undergoes the same metabolic pathway as corticosteroids after systemic administration. However, the systemic metabolism of clobetasol has not been fully characterized.

Clinical characteristics

Indications

The medicinal product is a highly active topical corticosteroid used in adults, elderly patients, 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 (except generalized plaque psoriasis).
• Dermatoses that are difficult to treat.
• Lichen planus.
• Discoid lupus erythematosus.
• Other skin diseases unresponsive to less potent corticosteroids.

Contraindications

• Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.
• Untreated skin infections.
• Rosacea.
• Acne vulgaris.
• Pruritus without inflammation.
• Perianal and genital pruritus.
• Perioral dermatitis.
• 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 can inhibit CYP3A4 (e.g., ritonavir, itraconazole) has been shown to inhibit corticosteroid metabolism, potentially leading to increased systemic effects. The clinical significance of such interaction depends on the dose, route of administration of the corticosteroid, 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 contained in the medicinal product. Local hypersensitivity reactions (see section "Side effects") 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 individuals 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. Sudden discontinuation of treatment may lead to glucocorticosteroid insufficiency (see section "Side effects").

The medicinal product contains:

• propylene glycol, which may cause skin irritation;
• cetyl stearyl 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 surfaces in contact with each other, such as 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 damaged skin or under other conditions involving impaired skin barrier function;

• pediatric age: 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 having an underdeveloped skin barrier and a larger skin surface area relative to body weight compared to adults.

Cases of serious osteonecrotic infections (including necrotizing fasciitis) and systemic immunosuppression (sometimes leading to reversible Kaposi's sarcoma-like lesions) have been reported following prolonged use of clobetasol propionate at doses exceeding the recommended (see section "Method of administration and dosage"). 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.

Use in children

The medicinal product is contraindicated in children under 1 year of age (see section "Contraindications").

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.

The use of the medicinal product in children should not exceed 5 days, if possible. The need for continued treatment should be reviewed weekly. The medicinal product must not be used under occlusive dressings in children.

Risk of infection with occlusive dressings

The risk of developing 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.

Use in psoriasis

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 the medicinal product for psoriasis treatment, the patient should be under close medical supervision.

Use in concomitant infections

Whenever treating inflammatory lesions with secondary infection, appropriate antibacterial therapy should be administered. If infection spreads, the use of the medicinal product should be discontinued and appropriate antibacterial treatment initiated.

Use in 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

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 the eyelids

When applying the cream to the eyelids, care should be taken to avoid the medicinal product entering the eyes, as repeated exposure may lead to cataracts and glaucoma.

If clobetasol gets into the eye, the affected eye should be rinsed thoroughly with large amounts of water.

Risk of visual disturbances

Visual disturbances may occur with both systemic and topical use of corticosteroids. If blurred vision or other visual disturbances develop, the patient should be referred to an ophthalmologist to evaluate possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and topical corticosteroid use.

Topical steroid withdrawal syndrome

Prolonged use of topical corticosteroids may lead to recurrent inflammation after discontinuation (topical steroid withdrawal syndrome). In severe cases, this manifests as dermatitis with intense redness, stinging, and burning, which may spread beyond the original treatment area. The risk increases with treatment of sensitive skin areas such as the face and skin folds. If the condition recurs days or weeks after successful treatment, withdrawal reaction should be suspected. Re-administration of the drug requires caution. In such cases, patients are advised to consult a specialist to reassess the therapeutic approach.

Warnings regarding excipients

The medicinal product contains: propylene glycol, which may cause skin irritation; chlorocresol, which may cause allergic reactions; polyoxyl 40 hydrogenated castor oil, which may cause skin reactions; cetyl stearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis).

The medicinal product contains paraffin. Patients should be warned about the risk of severe burns when smoking or being near open flames. Fabric (clothing, bed linen, dressings, etc.) that has come into contact with the medicinal product is more flammable and poses a serious fire hazard. Washing clothing and bed linen may reduce accumulation of the medicinal product but will not completely remove it.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of topical clobetasol in pregnant women are limited.

Topical application of corticosteroids in pregnant animals has resulted in fetal developmental abnormalities. The relevance of these findings to humans is unknown. The medicinal product 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 of treatment.

Period of breastfeeding

The safety of clobetasol use during breastfeeding has not been established. It is unknown whether topical corticosteroids may be systemically absorbed to an extent that measurable quantities appear in breast milk. The medicinal product may be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant. If used during breastfeeding, the cream should not be applied to the breasts to avoid accidental exposure of the infant’s mouth to the cream.

Effect on ability to drive and use machines

No studies have been conducted on the effect of the medicinal product on the ability to drive or operate machinery. Based on the adverse reaction profile of clobetasol, such effects are not expected.

Dosage and Administration

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 "Use in Specific Populations"). If treatment with a topical corticosteroid is clinically justified for longer than 4 weeks, consideration should be given to using a less potent corticosteroid.

Repeated, but short-term, courses of clobetasol propionate may be used to control exacerbations (see details below).

The medicinal product is intended for topical (cutaneous) use.

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

Apply the cream 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 achieved within a few days). Thereafter, reduce the frequency of application or switch to a less potent preparation. After each application of the cream, wait a certain period for complete absorption before applying an emollient. If the condition worsens or no improvement in clinical signs is observed within 2–4 weeks, the diagnosis and treatment should be re-evaluated.

Repeated short courses of treatment may be used to control exacerbations. Treatment should not last longer than 4 weeks. If continuous long-term treatment is required, less potent agents 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 cream 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 result. The improvement achieved is usually maintained by applying the cream without using an occlusive dressing.

Once control of the disease is achieved, the use of the medicinal product 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.

Dermatoses difficult to treat. Patients with frequent exacerbations

As soon as the 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. Such treatment has been shown to effectively reduce the frequency of exacerbations.

Continue to apply the cream to all previously affected skin areas or to known sites of potential exacerbation. This regimen should be combined with daily continuous use of emollients. The clinical condition, as well as the benefits and risks of continued treatment, should be regularly evaluated.

Use in elderly patients

Clinical studies have not revealed differences in response between elderly patients and younger patients. However, the higher prevalence of impaired liver or kidney function in elderly individuals may slow down the elimination of the drug in case of systemic absorption. Therefore, the minimum amount of the medicinal product for the shortest duration should be used to achieve the desired clinical effect.

Use in patients with renal/hepatic impairment

In case of systemic absorption (e.g., when applied over a large surface area for prolonged periods), metabolism and elimination may be slowed, increasing the risk of systemic toxicity. Therefore, the minimum amount of the medicinal product for the shortest duration should be used to achieve the desired clinical effect.

Children. The medicinal product 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, signs of hypercortisolism may occur in cases of chronic overdose or improper use.

Treatment

In case of overdose, the medicinal product should be gradually withdrawn by reducing the frequency of cream application or replacing it with a less potent corticosteroid, due to the risk of glucocorticosteroid insufficiency.

Further treatment should be carried out according to the patient's clinical condition or in accordance with current guidelines for the management 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 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000, including isolated cases), frequency not known (cannot be estimated based on available data).

Infections and infestations:

very rare – opportunistic infections.

Immune system disorders:

very rare – hypersensitivity, local hypersensitivity, generalized rash.

Endocrine system disorders:

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

Eye disorders:

very rare – glaucoma, cataract, central serous chorioretinopathy.

frequency not known – visual blurring.

Skin and subcutaneous tissue disorders:

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 psoriasis, erythema, rash, urticaria, acne;

frequency not known – withdrawal reaction: skin redness which may spread beyond the initial treated area, burning or prickling sensation, pruritus, skin desquamation, oozing pustules (see section "Special precautions for use").

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

General disorders and administration site conditions:

very rare – irritation/pain at the application site.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

After opening the tube, the medicinal product should be used within 3 months.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of the reach of children.

Packaging. 50 g in a tube; 1 tube per cardboard box.

Prescription status. Prescription only.

Manufacturer

WORLD MEDICINE ILAC SAN. VE TIC. A.S. /
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and place of business

COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey /
COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey.

Marketing Authorization Holder

WORLD MEDICINE, LLC, Ukraine /
WORLD MEDICINE, LLC, Ukraine.