Dermovate^® (Ointment, Cream) Instructions for Use

ATC Code

D07AD01 (Clobetasol)

Active Substance

Clobetasol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Topical corticosteroids for external use

Pharmacotherapeutic Group

Corticosteroids used in dermatology; very high-potency corticosteroids (group IV)

Pharmacological Action

Mechanism of action

Clobetasol is a topical corticosteroid that acts as an anti-inflammatory agent through several mechanisms of inhibiting the late phase of allergic reactions, including reducing mast cell density, reducing eosinophil chemotaxis and activation, reducing cytokine production by lymphocytes, monocytes, mast cells, and eosinophils, as well as suppressing arachidonic acid metabolism.

Pharmacodynamic effects

Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties.

Pharmacokinetics

Absorption

Topical corticosteroids can be systemically absorbed through intact healthy skin. The degree of percutaneous absorption of topical corticosteroids is determined by a number of factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation, and/or other pathological processes of the skin can also increase percutaneous absorption.

The mean C_max of clobetasol in plasma is reached 13 hours after the first application and 8 hours after repeated application of 30 g of clobetasol as 0.05% ointment to healthy skin and is 0.63 ng/ml. Ten hours after the application of the second dose (30 g) of clobetasol cream, its C_max slightly exceeds that of the ointment. In a separate study, 3 hours after a single application of 25 g of 0.05% clobetasol ointment in patients with psoriasis and eczema, C_max was 2.3 ng/ml and 4.6 ng/ml, respectively.

Metabolism

After absorption through the skin, topical corticosteroids are metabolized by the same pharmacokinetic pathways as systemic corticosteroids. They are metabolized mainly in the liver.

Excretion

Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Indications

Clobetasol is a highly active topical corticosteroid indicated for the short-term treatment of symptoms of inflammation and pruritus in dermatoses responsive to corticosteroid therapy and resistant to less active corticosteroids (for adults, elderly patients, and children over 1 year of age)

• Psoriasis (excluding widespread plaque psoriasis);
• Difficult-to-treat dermatoses;
• Lichen planus;
• Discoid lupus erythematosus;
• Other skin conditions resistant to therapy with less active corticosteroids.

ICD codes

Dosage Regimen

Cream

The drug is for external use.

The cream is recommended for skin lesions accompanied by weeping.

Adults, elderly patients, and children over 1 year of age

The drug should be applied in a thin layer and gently rubbed in, using the minimum amount sufficient to cover the entire affected area, once daily or twice daily until improvement occurs, then the frequency of application should be reduced or the drug should be replaced with a less potent one. After each application, the drug should be left on for a sufficient time to be absorbed before applying an emollient.

To prevent exacerbations of skin diseases, short (intermittent) courses of treatment with Dermovate^® are conducted.

For more resistant lesions, especially in the presence of hyperkeratosis, the effect of Dermovate^® topical cream can be enhanced, if necessary, by applying an occlusive dressing made of polyethylene film to the treatment site. Usually, applying an occlusive dressing overnight is sufficient to obtain a satisfactory response. Subsequently, improvement can usually be maintained by applying the drug without a dressing.

If the condition worsens or does not improve within 2-4 weeks, the diagnosis and treatment should be re-evaluated. Treatment should not continue for more than 4 weeks. If continuation of treatment is necessary, a less potent drug should be used.

The maximum dose should not exceed 50 g of cream per week.

Treatment with Dermovate^® should be gradually discontinued after disease control is achieved, and treatment with an emollient should be continued as maintenance therapy.

Abrupt withdrawal of Dermovate^® may lead to a recurrence of previously existing dermatoses.

Difficult-to-treat dermatoses (patients with frequent disease recurrences)

In case of acute disease, once the effect of a continuous course of treatment with Dermovate^® is achieved, the possibility of intermittent use of the drug (once daily, twice a week, without an occlusive dressing) may be considered. Such treatment has been shown to effectively reduce the frequency of relapse development.

Application of the drug should be continued to all previously affected areas of the skin or to known areas of potential exacerbation. This regimen should be combined with routine daily use of emollients. Regular assessment of the condition, as well as the benefits and risks of continuing treatment, should be carried out.

Use on the face

Use on the face is undesirable because this area is more susceptible to atrophic changes.

The course of treatment should be limited, if possible, to 5 days.

Occlusive dressings should not be used.

Special patient groups

Children

Dermovate^® topical cream is contraindicated in children under 1 year of age.

Children are more likely to develop local and systemic side effects during therapy with topical corticosteroids and generally require shorter courses of treatment using less potent agents than adults.

Caution should be exercised when using Dermovate^® in children to ensure the drug is applied in the minimum amount providing a therapeutic effect. The course of treatment in children should be limited, if possible, to 5 days; medical supervision is required at least once a week.

Occlusive dressings should not be used.

Elderly patients

Clinical studies have not revealed any differences in the efficacy of the drug in elderly and younger patients. The higher prevalence of reduced liver or kidney function in elderly patients may lead to slower elimination of the drug in case of its systemic absorption.

Consequently, the drug should be used in the minimum amount and for the shortest possible period, until the necessary clinical effect is achieved.

Patients with impaired renal and/or hepatic function

In case of systemic absorption of the drug (when applied to large skin surfaces for a prolonged period), its metabolism and excretion may slow down, leading to an increased risk of systemic side effects. Consequently, the drug should be used in the minimum amount and for the shortest possible period, until the necessary clinical effect is achieved.

Ointment

The drug is for external use.

The ointment is recommended for skin lesions accompanied by dryness, hyperkeratosis, and skin thickening.

Adults, elderly patients, and children over 1 year of age

The drug should be applied in a thin layer and gently rubbed in, using the minimum amount sufficient to cover the entire affected area, once daily or twice daily until improvement occurs, then the frequency of application should be reduced or the drug should be replaced with a less potent one. After each application, the drug should be left on for a sufficient time to be absorbed before applying an emollient.

To prevent exacerbations of skin diseases, short (intermittent) courses of treatment with Dermovate^® are conducted.

For more resistant lesions, especially in the presence of hyperkeratosis, the effect of Dermovate^® topical ointment can be enhanced, if necessary, by applying an occlusive dressing made of polyethylene film to the treatment site. Usually, applying an occlusive dressing overnight is sufficient to obtain a satisfactory response. Subsequently, improvement can usually be maintained by applying the drug without a dressing.

If the condition worsens or does not improve within 2-4 weeks, the diagnosis and treatment should be re-evaluated. Treatment should not continue for more than 4 weeks. If continuation of treatment is necessary, a less potent drug should be used.

The maximum dose should not exceed 50 g of ointment per week.

Treatment with Dermovate^® should be gradually discontinued after disease control is achieved, and treatment with an emollient should be continued as maintenance therapy.

Abrupt withdrawal of Dermovate^® may lead to a recurrence of previously existing dermatoses.

Difficult-to-treat dermatoses (patients with frequent disease recurrences)

In case of acute disease, once the effect of a continuous course of treatment with Dermovate^® is achieved, the possibility of intermittent use of the drug (once daily, twice a week, without an occlusive dressing) may be considered. Such treatment has been shown to effectively reduce the frequency of relapse development.

Application of the drug should be continued to all previously affected areas of the skin or to known areas of potential exacerbation. This regimen should be combined with routine daily use of emollients. Regular assessment of the condition, as well as the benefits and risks of continuing treatment, should be carried out.

Use on the face

Use on the face is undesirable because this area is more susceptible to atrophic changes.

The course of treatment should be limited, if possible, to 5 days.

Occlusive dressings should not be used.

Special patient groups

Children

Dermovate^® topical ointment is contraindicated in children under 1 year of age.

Children are more likely to develop local and systemic side effects during therapy with topical corticosteroids and generally require shorter courses of treatment using less potent agents than adults.

Caution should be exercised when using Dermovate^® in children to ensure the drug is applied in the minimum amount providing a therapeutic effect. The course of treatment in children should be limited, if possible, to 5 days; medical supervision is required at least once a week.

Occlusive dressings should not be used.

Elderly patients

Clinical studies have not revealed any differences in the efficacy of the drug in elderly and younger patients. The higher prevalence of reduced liver or kidney function in elderly patients may lead to slower elimination of the drug in case of its systemic absorption.

Consequently, the drug should be used in the minimum amount and for the shortest possible period, until the necessary clinical effect is achieved.

Patients with impaired renal and/or hepatic function

In case of systemic absorption of the drug (when applied to large skin surfaces for a prolonged period), its metabolism and excretion may slow down, leading to an increased risk of systemic side effects. Consequently, the drug should be used in the minimum amount and for the shortest possible period, until the necessary clinical effect is achieved.

Adverse Reactions

The adverse events listed below are presented according to the affected organ systems and frequency of occurrence. Frequency is defined as follows: 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). Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance.

Post-marketing surveillance data

Infections and infestations very rare – opportunistic infections.

Immune system disorders very rare – hypersensitivity, generalized rash.

Endocrine disorders very rare – suppression of the hypothalamic-pituitary-adrenal system, Cushing’s syndrome (hypercortisolism syndrome) (e.g., moon face, central obesity), impaired weight gain and/or growth retardation in children, osteoporosis, glaucoma, hyperglycemia and/or glucosuria, cataract, increased blood pressure, weight gain or obesity, decreased endogenous cortisol concentration, alopecia, brittle hair.

Skin and subcutaneous tissue disorders common – itching, burning sensation and/or pain; uncommon – local skin atrophy*, striae*, telangiectasia*; very rare – skin thinning*, skin wrinkling*, dry skin*, pigmentation changes*, hypertrichosis, exacerbation of disease symptoms, allergic contact dermatitis and/or dermatitis, pustular psoriasis, erythema, rash, urticaria, acne.

Other: very rare – irritation and/or pain at the application site.

* Skin manifestations are secondary to local and/or systemic effects of hypothalamic-pituitary-adrenal system suppression.

Contraindications

• Untreated skin infections;
• Rosacea;
• Acne;
• Perioral dermatitis;
• Pruritus without inflammation;
• Perianal and genital pruritus;
• Children under 1 year of age;
• Breastfeeding period;
• Hypersensitivity to clobetasol or any other component of the drug.

With caution increased local sensitivity to corticosteroids or to any excipient in the drug; psoriasis; children from 1 year to 18 years of age.

Use in Pregnancy and Lactation

Fertility

There are no data to assess the effect of topical corticosteroids on human fertility.

When administered subcutaneously to rats, Clobetasol did not affect mating ability, but when the drug was used at the highest dose, a decrease in fertility was noted.

Pregnancy

Data on the use of clobetasol in pregnant women are limited. Topical application of corticosteroids in pregnant animals may cause fetal developmental disorders. The significance of these data for humans has not been established.

The use of clobetasol during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.

The minimum amount of the drug should be used for the minimum period of time.

Breastfeeding period

The use of the drug during breastfeeding is contraindicated.

Use in Hepatic Impairment

In patients with impaired liver function, the drug should be used in the minimum amount and for the shortest possible period, while ensuring the necessary clinical effect is achieved.

Use in Renal Impairment

In patients with impaired renal function, the drug should be used in the minimum amount and for the shortest possible period, while ensuring the necessary clinical effect is achieved.

Pediatric Use

The use of the drug is contraindicated in children under 1 year of age.

Geriatric Use

In elderly patients, the drug should be used in the minimum amount and for the shortest possible period, while ensuring the necessary clinical effect is achieved.

Special Precautions

Since the drug in the form of an ointment helps retain moisture in the skin, Dermovate^® topical ointment is recommended for skin lesions accompanied by dryness, hyperkeratosis, and thickening.

Local hypersensitivity reactions may resemble the symptoms of the underlying disease.

In some individuals, as a result of increased systemic absorption of topical corticosteroids, manifestations of hypercortisolism (Cushing’s syndrome) and reversible suppression of the hypothalamic-pituitary-adrenal system may occur, leading to the development of glucocorticoid deficiency. If any of the above disorders are observed, the drug should be discontinued by gradually reducing the frequency of its application, or replaced with a less potent corticosteroid. Abrupt cessation of treatment may lead to the development of glucocorticoid deficiency.

Risk factors for increased systemic effects include: the potency of the topical corticosteroid and the composition of the topical medicinal product, the duration of use, application to large areas of the skin, use on occluded areas of the skin (for example, on areas with diaper rash or under an occlusive dressing (diapers and nappies in infants can act as an occlusive dressing)), increased hydration of the stratum corneum, use on areas with thin skin such as the face, application to damaged skin or in other conditions that may be accompanied by impaired skin barrier integrity. Compared to adults, children and infants may exhibit a greater degree of absorption of topical corticosteroids, making this patient category more susceptible to the risk of developing systemic side effects. This is due to the fact that children have an immature skin barrier and a larger body surface area to body weight ratio compared to adults.

Use in children

Compared to adults, infants and older children may absorb a proportionally greater amount of topical corticosteroids, as a result of which patients in this group may be more susceptible to systemic adverse effects.

Long-term treatment with topical corticosteroids in children under 12 years of age should be avoided whenever possible, as prolonged topical use of corticosteroids can cause suppression of adrenal function.

Atrophic skin changes occur more frequently in children than in adults with topical corticosteroid use. If clobetasol propionate is prescribed to children, the course of treatment should be limited to 5 days, and medical supervision is required at least once a week. Occlusive dressings should not be used.

Use in psoriasis

Topical corticosteroids should be used with caution in the treatment of psoriasis, as in some cases, recurrence of the disease, development of tolerance to the drug, risk of generalized pustular psoriasis, and development of local or systemic toxic reactions due to impaired skin barrier function have been reported. Careful patient monitoring is important when used for the treatment of psoriasis.

Concomitant infection

If a secondary infection occurs, appropriate antibacterial therapy should be administered. If any signs of infection spreading appear, topical corticosteroid use should be discontinued and appropriate treatment with antibacterial drugs should be initiated.

Risk of infection development under occlusion

Warm, moist conditions in skin folds, as well as conditions created by the application of an occlusive dressing, promote the development of bacterial infection. When using an occlusive dressing, the skin should be cleaned before applying a new dressing.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat dermatitis around chronic leg ulcers. However, such use may be accompanied by an increased frequency of local hypersensitivity reactions and an increased risk of developing local infections.

Application to facial skin

Application to facial skin is undesirable because this area is more prone to the development of atrophic changes. If application to facial skin is necessary, treatment should be limited to 5 days.

Application to eyelids

If application to the eyelids is necessary, care must be taken to prevent the product from getting into the eyes, as repeated exposure may lead to the development of cataracts and glaucoma. If the product accidentally gets into the eyes, they should be rinsed thoroughly with water.

Effect on ability to drive and operate machinery

Studies on the effect of clobetasol on the ability to drive vehicles or operate machinery have not been conducted. Based on the side effect profile of topical clobetasol, no adverse effect on such activities is expected.

Overdose

Symptoms: Dermovate^® may be absorbed in sufficient amounts upon topical application to cause systemic effects. The development of acute overdose is unlikely. However, in case of chronic overdose or improper use of Dermovate^®, symptoms of hypercorticism may develop.

Treatment: In case of overdose, the product should be gradually withdrawn, by reducing the frequency of application or substituting it with a less potent corticosteroid, under medical supervision due to the risk of adrenal insufficiency. Further treatment should be carried out according to the clinical situation or as recommended by poison control centers if available.

Drug Interactions

Concomitant use of drugs that can inhibit the CYP3A4 isoenzyme (e.g., ritonavir and itraconazole) has been shown to inhibit the metabolism of corticosteroids, leading to an increase in their systemic exposure. The degree of clinical significance of this interaction depends on the dose and route of administration of the corticosteroid and the potency of the CYP3A4 isoenzyme inhibitor.

Storage Conditions

The product should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life is 2 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The product is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.