Betazon ultra

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BETAZONE ULTRA (BETAZONE ULTRA)

Composition:

Active substances: betamethasone, clotrimazole, gentamicin;

1 g of the preparation contains micronized betamethasone dipropionate equivalent to betamethasone 0.5 mg, clotrimazole 10 mg, gentamicin sulfate equivalent to gentamicin 1 mg;

Excipients: mineral oil, white soft paraffin.

Pharmaceutical form. Ointment.

Main physicochemical properties: ointment from white to light yellow in color, of uniform consistency.

Pharmacotherapeutic group. Corticosteroids for dermatological use. Corticosteroids in combination with antibiotics. Betamethasone and antibiotics. ATC code D07C C01.

Pharmacological properties.

Pharmacodynamics. The drug combines the anti-inflammatory effect of betamethasone dipropionate with the antibacterial activity of gentamicin sulfate and the antifungal action of clotrimazole.

Betamethasone dipropionate is a potent (class III) corticosteroid with anti-inflammatory, antiallergic, and antipruritic effects.

Gentamicin is an antibiotic from the aminoglycoside group with bactericidal activity. It inhibits protein synthesis in antibiotic-sensitive microorganisms. Gentamicin is active against many aerobic gram-negative and a few gram-positive bacteria. In vitro, gentamicin at concentrations of 1–8 mcg/mL inhibits most sensitive strains of Escherichia coli, Haemophilus influenzae, Moraxella lacunata, Neisseria, indole-positive and indole-negative strains of Proteus, Pseudomonas (including most strains of Pseudomonas aeruginosa), Staphylococcus aureus, Staphylococcus epidermidis, and Serratia. Different species and strains of the same species may show significant differences in in vitro sensitivity. Moreover, in vitro sensitivity does not always correlate with in vivo sensitivity. Gentamicin is ineffective against most anaerobic bacteria, fungi, and viruses. Gentamicin has only minimal efficacy against streptococci. Resistance to gentamicin may develop in both gram-negative and gram-positive bacteria.

Clotrimazole is a synthetic antifungal agent from the imidazole derivatives group. Its spectrum of activity includes a range of fungi pathogenic to humans and animals. Clotrimazole provides effective action against dermatophytes, yeasts, and molds. In vitro studies have demonstrated clotrimazole's efficacy against Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, and Candida (including Candida albicans). Based on current knowledge, the antifungal effect of clotrimazole is due to inhibition of ergosterol synthesis. Ergosterol is an essential component of the fungal cell membrane.

Pharmacokinetics. Studies on penetration or absorption of this medicinal product have not been conducted.

Betamethasone. Under normal conditions, only a portion of topically applied betamethasone is systemically available. The extent of its penetration depends on the site of application, skin condition, pharmaceutical formulation used, patient's age, and method of application.

Gentamicin. Absorption can be disregarded when gentamicin is applied to intact skin. However, increased transdermal absorption should be considered in cases of loss of the keratin layer, inflammatory conditions, and when applied under occlusive dressing or over large skin areas.

Clotrimazole. After application, systemic absorption is low, with most of the clotrimazole remaining in the stratum corneum. Such concentrations were observed 6 hours after application of 1% radiolabeled clotrimazole to intact skin and skin with acute inflammation: stratum corneum – 100 mcg/cm³, reticular layer – 0.5–1 mcg/cm³, subcutaneous layer – 0.1 mcg/cm³.

Clinical characteristics.

Indications. Treatment of dermatoses sensitive to corticosteroids, when (or suspected of) bacterial and/or fungal infections caused by microorganisms sensitive to the components of the drug.

Contraindications. Contraindications for topical use of corticosteroids include skin infections [viral, bacterial (including tuberculosis), and fungal origin], skin reactions following vaccination, skin ulcers, and acne. The ointment should not be applied in cases of rosacea or perioral dermatitis. The drug is contraindicated in patients with hypersensitivity to the active substances or to any other component of the drug, other aminoglycoside antibiotics (cross-allergic reactions to gentamicin), or imidazole derivatives (cross-allergic reactions to clotrimazole).

The drug is not indicated for use under occlusive dressings.

The drug should not be applied to mucous membranes, eyes, or the area around the eyes.

Interaction with other medicinal products and other forms of interaction. When the ointment is used on genital skin and the anal area, the presence of soft paraffin or liquid paraffin (excipients in the drug formulation) may reduce the tensile strength of latex condoms, thereby decreasing their reliability during use.

Topically applied clotrimazole may act as an antagonist to amphotericin and other polyene antibiotics.

Special precautions for use.

The ointment is particularly suitable for application to dry or thickened skin. The product is not intended for ophthalmic use.

If skin irritation or signs of hypersensitivity develop during treatment with the ointment, the use of the product should be discontinued and appropriate therapy should be initiated for the patient.

With topical application, systemic absorption of active ingredients may be increased when the product is applied over large skin areas, with prolonged use, or on damaged skin. In such cases, adverse effects typical of systemic exposure to the active ingredients may occur. When aminoglycoside antibiotics are administered systemically concomitantly, the possibility of cumulative toxic effects (ototoxicity/nephrotoxicity) should be considered in case of increased absorption.

Particular attention should be paid to potential cross-allergic reactions with other aminoglycoside antibiotics.

Prolonged topical use of antibiotics may occasionally lead to the overgrowth of resistant microorganisms. In such cases, as well as in the event of superinfection, appropriate treatment should be initiated.

The use of the medicinal product in high doses, over large body surface areas, or the use of potent or very potent corticosteroids should be performed only under regular medical supervision, particularly regarding suppression of the hypothalamic-pituitary-adrenal (HPA) axis and possible metabolic effects.

Application of the product to open wounds or damaged skin should be avoided.

Continuous treatment for longer than 2–3 weeks is not recommended.

Very potent, potent, and moderately potent corticosteroids should be used with caution when applied to facial or genital skin. In such cases, the treatment course should not exceed 1 week.

Corticosteroids may mask symptoms of an allergic reaction to one of the components of the product. The patient should be instructed to use the product only for personal treatment of the existing skin condition and not to share it with others.

When using systemic and topical corticosteroids (including intranasal, inhaled, and intraocular administration), visual disturbances may occur. If symptoms such as blurred vision or other visual disturbances occur, the patient should undergo an ophthalmological examination to evaluate possible causes of visual impairment, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and topical corticosteroid use.

Children. Pediatric patients may demonstrate greater sensitivity to hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing's syndrome caused by topical corticosteroids compared to adult patients, due to a higher skin surface area to body weight ratio.

In children treated with topical corticosteroids, suppression of HPA axis function, Cushing's syndrome, growth retardation, inadequate weight gain, and increased intracranial pressure have been reported.

Signs of adrenal cortex function suppression include low plasma cortisol levels and lack of response to adrenocorticotropic hormone (ACTH) stimulation tests. Increased intracranial pressure may manifest as bulging fontanelle, headache, and bilateral optic disc swelling.

Use during pregnancy or breastfeeding. It is known from animal experimental studies that topically applied corticosteroids have teratogenic effects. There are no data on the use of this product during pregnancy in humans.

Aminoglycosides cross the placental barrier and may cause harm to the fetus when administered to pregnant women. Cases of complete, irreversible, bilateral congenital deafness in children whose mothers received aminoglycosides (including gentamicin) during pregnancy have been reported. There is insufficient data on the topical use of gentamicin in pregnant women. There is insufficient data on the use of clotrimazole in pregnant women.

Animal studies have not demonstrated any risk of adverse effects of the product on the fetus.

The product should be used only if clearly needed. It should not be used in large doses, over large skin areas, or for prolonged periods.

It is unknown whether gentamicin, clotrimazole, and corticosteroids can penetrate into breast milk following topical application. However, systemic corticosteroids are known to be excreted in breast milk.

The ointment should not be applied to the breasts during breastfeeding.

Ability to influence reaction speed when driving or operating machinery. The effect on the ability to drive or operate machinery has not been studied.

Dosage and Administration

For adults, apply a thin layer to the entire affected area and surrounding skin twice daily, in the morning and evening, and rub in gently. The duration of treatment depends on the patient's clinical response as well as clinical and microbiological findings.

In cases of athlete's foot, a longer treatment course may be required (2–4 weeks).

Children. Not recommended for use in children, as there is no experience with the use of the drug in this age group.

Overdose. Prolonged or excessive use of topical glucocorticosteroids may lead to suppression of the hypothalamic-pituitary-adrenal system, resulting in secondary adrenal insufficiency and symptoms of hypercorticism, including Cushing's syndrome.

It cannot be excluded that a single overdose of gentamicin may lead to symptoms of overdose.

Excessive and prolonged use of gentamicin may result in overgrowth of antibiotic-resistant microorganisms at the site of skin infection.

Treatment. Administer appropriate symptomatic therapy. Symptoms of acute hypercorticism are usually reversible. If necessary, correct the electrolyte balance. In cases of chronic toxic effects, gradual withdrawal of corticosteroids is recommended.

In case of overgrowth of resistant microorganisms, discontinue treatment with the drug and initiate appropriate antifungal or antibacterial therapy.

Adverse Reactions

At the beginning of treatment, the following undesirable effects may occur:

Skin reactions: skin irritation, burning sensation, itching, dryness of the skin, hypersensitivity reactions to one of the components of the drug, and changes in skin color.

When applied over large areas of skin, under occlusive dressings and/or for prolonged periods, local skin changes may occur. Systemic reactions (adrenal suppression) may occur when applied over large skin areas.

One should bear in mind the increased risk of secondary infections due to reduced local resistance to infection.

Skin reactions: localized skin changes such as skin atrophy (especially on the face), telangiectasia, striae, stretch marks, subcutaneous hemorrhages, purpura, steroid-induced acneiform eruptions, rosacea-like/perioral dermatitis, hypertrichosis, and changes in skin color. It is unknown whether these skin color changes are reversible. Contact sensitization to gentamicin may occur.

In some patients, possible photosensitization has been observed; however, this effect does not recur upon repeated application of gentamicin followed by ultraviolet radiation exposure.

Endocrine system: suppression of endogenous corticosteroid synthesis, adrenal hyperactivity with edema.

Metabolic effects: development of latent diabetes mellitus.

Eye disorders: blurred vision.

Ear, inner ear/kidney disorders: when used concomitantly with systemic aminoglycoside antibiotics, combined ototoxicity/nephrotoxicity may occur when the ointment is applied over large body surfaces or over areas of damaged skin.

Musculoskeletal system: osteoporosis, growth retardation (in children).

Shelf life: 3 years.

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

Packaging: 15 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 activity:

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

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

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

(all stages of manufacturing, batch release)