Metizolon

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MЕТИЗОЛОН (METIZOLONE)

Composition:

Active substance: methylprednisolone;

1 g of the preparation contains micronized methylprednisolone acetonide 1 mg;

Excipients: butylhydroxyanisole (E 320), isopropyl myristate, white soft paraffin, peach oil, glycerol monostearate, cetyl stearyl alcohol, polyethylene glycol stearate, disodium edetate, glycerin, benzyl alcohol, purified water.

Pharmaceutical form. Topical cream.

Main physicochemical properties: opaque white cream of homogeneous consistency with a faint odor.

Pharmacotherapeutic group. Dermatological corticosteroids.

ATC code D07A C14.

Pharmacological properties.

Pharmacodynamics.

Methylprednisolone aceponate (6α-methylprednisolone aceponate) is a non-halogenated synthetic corticosteroid molecule characterized by a high degree of dissociation between its local and systemic effects.

The 6α-methyl group provides a potentiating effect, while the lipophilic ester groups ensure better skin penetration.

The local anti-inflammatory effect, confirmed by pharmacological and clinical-pharmacological studies, is comparable to that of more potent corticosteroids. Systemic effects of methylprednisolone aceponate following topical application are minimal, according to study data.

Pharmacokinetics.

• The active ingredient of the medicinal product rapidly penetrates through the skin, but absorption is weak (<1% of the applied dose within 24 hours on intact skin without occlusion; 3% with occlusion).
• Transdermal absorption during treatment using higher doses in patients with atopic dermatitis and psoriasis amounts to 2.5% in adults and 0.5–2% in children.
• In human skin, the active ingredient undergoes hydrolysis, forming a highly active metabolite with increased affinity for intracellular receptors. This metabolite is rapidly inactivated via glucuronic conjugation immediately after absorption. In humans, following intravenous administration, excretion of inactive metabolites occurs in a ratio of 1:5 between urinary and fecal elimination. The elimination half-life is approximately 16 hours, and plasma protein binding is 90%.
• Any possibility of accumulation is excluded.

Clinical characteristics.

Indications.

Atopic dermatitis (neurodermatitis, endogenous eczema); true (actual) eczema; simple contact dermatitis and allergic contact dermatitis; dyshidrotic eczema, infantile eczema, seborrheic dermatitis (and eczema), including on the scalp; nummular eczema, inflammatory scalp dermatoses associated with pruritus.

Contraindications.

• Hypersensitivity to methylprednisolone aceponate or to any other component of the medicinal product;
• tuberculous or syphilitic processes in the area of application; viral infections (e.g., varicella, herpes zoster), rosacea, perioral dermatitis, skin ulcers, acne vulgaris, atrophic dermatitis, or skin reactions following vaccination at the site of application.

Interaction with other medicinal products and other forms of interaction. No data available.

Due to absorption, treatment of large skin areas or prolonged therapy may potentially lead to interactions similar to those observed during systemic therapy. However, such interactions have not been reported to date.

If concomitant use of any other medicinal products is necessary, consult a physician.

Special precautions for use

When treating a pathological process over a large skin area, the duration of therapy should be strictly defined by a physician.

In bacterial infections of the skin and/or in case of fungal involvement, additional specific treatment with antibacterial and/or antifungal agents is required.

The drug should be avoided from contact with eyes and application on deep open wounds or mucous membranes.

When methylprednisolone aceponate in the form of a hydrophobic cream was applied over 60% of the body surface under occlusive dressing for 22 hours in healthy adults, a decrease in plasma cortisol levels and disruption of its circadian rhythm were observed. However, when the drug was applied over a large skin area (40–90% of body surface) without occlusion in children (in newborns, diapers may act as occlusive dressing), no impairment of adrenal cortex function was observed. Nevertheless, when applying the drug over a large skin area, the treatment duration should be kept as short as possible.

The risk of adverse effects significantly increases when topical corticosteroids are applied over large body areas or for prolonged periods, especially under occlusive dressings.

If excessive skin dryness occurs during prolonged use of the drug, it is recommended to switch to another dosage form of methylprednisolone aceponate with a higher fat content.

As with systemic corticosteroids, topical corticosteroids may also lead to glaucoma (e.g., after high-dose use or prolonged application over large areas, use of occlusive dressings, or application around the eyes).

Prolonged use of topically applied drugs may lead to sensitization. In such cases, therapy should be discontinued and appropriate treatment initiated.

The drug contains cetyl stearyl alcohol and butylated hydroxyanisole, which may cause local skin reactions (e.g., contact dermatitis); butylated hydroxyanisole may also cause irritation of eyes and mucous membranes.

Use during pregnancy or breastfeeding. This drug should not be used during pregnancy or breastfeeding unless clearly needed and under strict medical supervision. Prolonged use or application over large body areas should be avoided.

During the first trimester of pregnancy, topical use of corticosteroid-containing drugs should be avoided. Throughout pregnancy, treatment of large skin areas, prolonged use of the drug, or its use under occlusive dressings should be avoided.

Some epidemiological studies suggest a possible increased risk of cleft palate in newborns whose mothers received corticosteroid treatment during the first trimester of pregnancy. Cleft palate is a very rare condition. Considering the possible teratogenic effect of systemic corticosteroids, their impact may be estimated as an increase of 1–2 cases per 1000 women exposed to such treatment during pregnancy.

There are currently no reliable data on the use of this drug during pregnancy; however, a minimal risk is expected due to the very low likelihood of systemic effects of topically applied corticosteroids.

This drug should be prescribed to pregnant women only after careful assessment of the benefit-risk ratio.

Animal studies have shown that methylprednisolone aceponate does not penetrate into breast milk. However, it is unknown whether methylprednisolone aceponate passes into human breast milk, as systemically administered corticosteroids have been detected in women's breast milk. It is also unknown whether topical application of the drug may lead to systemic absorption of methylprednisolone aceponate in amounts detectable in human breast milk. Therefore, the drug should be used with caution in women who are breastfeeding.

During breastfeeding, the drug should not be applied to the breasts. Prolonged use, application over large skin areas, or use under occlusive dressings should be especially avoided.

There is no information available on the effects of methylprednisolone aceponate on fertility.

Ability to affect reaction speed when driving or operating machinery. Not established.

Dosage and Administration

The product should usually be applied once daily as a thin layer to the affected skin areas, unless otherwise directed by a physician.

The formulation of the product (1 g of cream contains 1 mg of methylprednisolone aceponate), due to its increased water content, facilitates exudate drainage and is therefore particularly suitable for the treatment of weeping eczematous lesions in the acute phase, as well as skin areas with maceration, whether hairy or non-hairy.

The duration of treatment in ordinary cases should not exceed 12 weeks in adults and 4 weeks in children. There are no data on the safety of using the product in children under 4 months of age.

When treating children aged 4 months and older, no dose adjustment is required.

Children. There are no data on the safety of using the product in children under 4 months of age.

When treating children aged 4 months and older, no dose adjustment is necessary.

The duration of treatment in children should not exceed 4 weeks in ordinary cases.

Overdose.

In cases of cutaneous atrophoderma associated with overdose during topical application of the product, treatment should be discontinued. Symptoms usually regress within 10–14 days.

Adverse reactions.

General disorders and application site reactions: burning and itching at the application site, dryness, erythema, vesicles, follicular inflammation (folliculitis), rash, paraesthesia at the application site.

Skin and subcutaneous tissue disorders: pyoderma, skin fissures, telangiectasia, skin atrophy (thinning of the skin), fungal infections, acne.

Immune system disorders: hypersensitivity to the medicinal product.

Rarely, when using this medicinal product, the following adverse reactions may occur: bacterial cellulitis and skin infections.

As with topical application of other corticosteroids, the following adverse effects may also be observed: development of striae at the application site, excessive hair growth (hypertrichosis), perioral dermatitis, skin discoloration, contact dermatitis, and allergic skin reactions to any of the components of the medicinal product.

In individual cases, systemic effects of corticosteroids may occur due to their absorption.

If any adverse reactions occur, use of the medicinal product should be discontinued and medical advice must be sought immediately.

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. 15 g in a tube in a carton.

Supply classification. Over-the-counter (without prescription).

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.

(all manufacturing stages, quality control, batch release)

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

(all manufacturing stages, batch release)