Belogent

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BELOGENT (BELOGENT®)

Composition:

Active substances: betamethasone dipropionate, gentamicin sulfate;

1 g of ointment contains 0.640 mg betamethasone dipropionate, equivalent to 0.500 mg betamethasone; 1.66 mg gentamicin sulfate, equivalent to 1.00 mg gentamicin;

Excipients: mineral oil, white soft paraffin.

Pharmaceutical form. Ointment.

Main physicochemical properties: white, semitransparent, homogeneous ointment.

Pharmacotherapeutic group. Corticosteroids for dermatological use. Potent corticosteroids in combination with antibiotics. ATC code D07C C01.

Pharmacological Properties

Pharmacodynamics

Betamethasone dipropionate is a synthetic fluorinated derivative of hydrocortisone. It readily penetrates the skin, exerting potent local anti-inflammatory, antipruritic, and antiallergic effects. It eliminates the causes of inflammatory processes, inhibits histamine release, and prevents the development of local allergic symptoms. Due to its local vasoconstrictive action, it reduces exudative reactions.

Gentamicin is an aminoglycoside antibiotic with pronounced bactericidal activity. It belongs to broad-spectrum antibiotics and exhibits antibacterial activity against Gram-negative bacteria (e.g., Proteus, Escherichia coli) and certain Gram-positive bacteria, including penicillin-resistant staphylococci.

Cross-resistance between gentamicin and other aminoglycosides has been observed.

Pharmacokinetics

Betamethasone dipropionate is not biotransformed in the skin. After penetration through the skin into the body (absorption not exceeding 1%) it is metabolized in the liver and primarily excreted via urine, with a smaller amount eliminated through bile. Absorption of betamethasone dipropionate through the skin increases when applied to delicate skin, skin folds, or skin with damaged epidermis or inflammation. Furthermore, absorption increases with more frequent application and after application over large skin areas. Transdermal absorption of betamethasone dipropionate is more pronounced in younger individuals compared to adults.

Gentamicin sulfate is not absorbed through intact skin following topical application. However, systemic absorption may occur when applied to skin damaged by trauma, burns, or ulcers. Gentamicin sulfate is not biotransformed in the body and is excreted unchanged in urine.

Clinical characteristics.

Indications.

Dermatoses amenable to treatment with glucocorticosteroids complicated by, or suspected of being complicated with, secondary infection caused by gentamicin-sensitive microorganisms: eczema (atopic, nummular), anogenital and senile pruritus, contact dermatitis, seborrheic dermatitis, neurodermatitis, intertriginous dermatitis, solar dermatitis, exfoliative dermatitis, stasis dermatitis, and psoriasis.

Contraindications.

Belogent is contraindicated in patients with hypersensitivity to betamethasone dipropionate, gentamicin, or any other component of the medicinal product, as well as in patients with hypersensitivity to other glucocorticoids or aminoglycoside antibiotics.

The drug is contraindicated during pregnancy.

Belogent ointment is also contraindicated in the following cases:

• viral infections, including post-vaccination reactions and varicella;
• cutaneous tuberculosis and syphilis;
• widespread plaque psoriasis;
• varicose veins;
• perioral dermatitis;
• skin neoplasms;
• viral skin infections (e.g., herpes simplex, herpes zoster);
• acne rosacea and rosacea-like dermatitis;
• dermatomycoses;
• other bacterial and fungal skin infections in the absence of appropriate antibacterial and antifungal therapy;
• ophthalmological diseases;
• concomitant systemic therapy with aminoglycoside antibiotics — risk of achieving toxic plasma levels;
• progressive renal insufficiency;
• children under 1 year of age.

Belogent ointment must not be applied into the auditory canal, eyes, or onto mucous membranes.

Due to the potential for absorption of the active substance, prolonged treatment, application over large skin areas, and use under occlusive dressings should be avoided.

Interaction with other medicinal products and other types of interactions.

No interactions have been observed with topical application of glucocorticosteroids. However, vaccination against smallpox and other types of immunization (especially during prolonged treatment over large skin areas) are not recommended during treatment due to the possible lack of an adequate immunological response, such as production of specific antibodies.

Belogent may enhance the effect of immunosuppressive agents and reduce the effect of immunostimulatory drugs.

Concomitant use with other dermatological products is not recommended, as it may reduce the efficacy of Belogent.

Gentamicin interacts with amphotericin B, heparin, sulfadiazine, and beta-lactam antibiotics (e.g., cephalosporins).

Special precautions for use.

Do not use continuously for more than 2 weeks. If skin irritation or signs of hypersensitivity develop during treatment, the ointment should be discontinued and appropriate therapy should be selected for the patient.

Medicinal products containing gentamicin should be selected cautiously for specific therapy. They should be used only if there is no rapid response to antiseptic measures, if such response is insufficient, or if antiseptic therapy is contraindicated.

Prolonged use of the drug on large areas of skin increases the frequency of adverse reactions and the possibility of developing bacterial resistance to gentamicin sulfate.

Cross-allergic reactions with aminoglycoside antibiotics have been observed.

Caution is required when using this medicinal product because it contains gentamicin. Prior to use, hypersensitivity to antibiotics should be assessed, and situations in which antibiotic therapy is contraindicated should be identified. Any adverse effects observed during systemic use of glucocorticoids, including suppression of adrenal cortex function, may also occur with topical application of glucocorticoids following systemic absorption, especially in children.

Systemic absorption of topical glucocorticoids generally increases with higher glucocorticoid doses, longer duration of treatment, and larger treated body surface area. Therefore, patients using high doses of potent glucocorticoids over large body areas should be closely monitored for early detection of signs of hypothalamic-pituitary-adrenal (HPA) axis suppression. If HPA axis suppression develops, Belogent ointment should be discontinued, the frequency of application reduced, or the patient switched to a less potent glucocorticoid. In rare cases, withdrawal symptoms may develop, requiring the addition of systemic glucocorticoid therapy.

The use of gentamicin in treating skin infections carries a risk of allergic reactions. Gentamicin is a contact allergen with a sensitization rate of approximately 1.4%. The risk of allergy increases with the duration of therapy. An allergic reaction resulting from topical application of gentamicin is a contraindication for systemic use of gentamicin and other aminoglycosides.

If infection develops at the site of ointment application, appropriate antibacterial or antifungal treatment should be initiated.

If infection symptoms do not resolve, the use of the drug should be discontinued during the period of infection treatment.

Do not apply the medicinal product to facial skin due to the risk of adverse effects (e.g., telangiectasia, perioral dermatitis), even after short-term use. The ointment is not intended for ophthalmic use.

Use with caution in patients with psoriasis, as topical application of glucocorticoids to psoriatic lesions may lead to exacerbation of relapse due to tolerance development, generalized pustular psoriasis, and systemic toxicity caused by impaired skin barrier function.

Use in the groin and genital areas only when strictly necessary, as increased absorption and the development of adverse effects (e.g., telangiectasia, perioral dermatitis) are possible, even after short-term use.

Use with caution in patients with pre-existing atrophic subcutaneous tissue conditions, especially in elderly individuals.

Do not apply the ointment under occlusive dressings, as this may lead to epidermal atrophy, striae formation, and secondary infection.

Prolonged topical use of antibiotics may occasionally lead to overgrowth of resistant microorganisms, including fungi. In such cases, as well as in the event of skin irritation, sensitization, or superinfection, treatment with the drug should be discontinued and appropriate therapy initiated.

Systemic absorption of gentamicin during topical application may be higher when treating large body surfaces, particularly during prolonged use or in the presence of skin damage. In such cases, adverse effects associated with systemic gentamicin use may occur. Under these conditions, gentamicin should be used cautiously, especially in children.

Due to the potential for neuromuscular blockade with systemically absorbed aminoglycosides, the medicinal product should be used with caution in patients with myasthenia gravis, Parkinson’s disease, other conditions associated with muscle weakness, and in patients concurrently receiving other medicinal products that may cause neuromuscular blockade.

Due to the presence of white soft paraffin and mineral oil in the ointment formulation, application in the anogenital area may damage the structure of latex condoms and reduce their effectiveness during treatment.

Visual disturbances

Visual disturbances may occur with systemic and topical use of corticosteroids (including intranasal, inhaled, and intraocular administration). 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 use of corticosteroids.

Use during pregnancy or breastfeeding.

Pregnancy.

The medicinal product is contraindicated during pregnancy. There are no data on the topical use of betamethasone and gentamicin in pregnant women. Gentamicin can cross the placental barrier and accumulate in fetal tissues. Reproductive toxicity has been demonstrated in animal studies. Some studies have shown embryotoxic and teratogenic effects after systemic and topical use of betamethasone. There may be an increased risk of congenital malformations with systemic use of corticosteroids, particularly during the first trimester of pregnancy.

Breastfeeding.

It is unknown whether the drug passes into breast milk after topical application; therefore, it is not recommended for use during breastfeeding. Contact between the treated skin area and the infant should be avoided.

Ability to affect reaction speed when driving or operating machinery.

The drug does not affect reaction speed when driving or operating machinery.

Dosage and Administration.

Apply the ointment as a thin layer to the entire affected skin area twice daily – in the morning and in the evening.

The frequency of application is determined individually depending on the severity of the disease. In mild cases, apply once daily; in more severe cases, more frequent application may be required.

The duration of treatment depends on the size and location of the lesion, as well as on the patient's response to therapy.

If no clinical improvement is observed within 3–4 weeks, the physician should reconsider the diagnosis.

Children.

There are no clinical data on the use of this medicinal product in children; therefore, its use in this age group is not recommended.

In children, the body surface area to body weight ratio is higher than in adults, resulting in more intensive absorption of the drug. Children are more susceptible to hypothalamic-pituitary-adrenal (HPA) axis suppression and the development of exogenous corticosteroid effects.

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

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

Overdose.

With prolonged or excessive use over large skin areas, high doses, or use under occlusive dressings, overdose symptoms may occur, manifested by an increase in systemic adverse effects typical of corticosteroids (hyperglycemia, glucosuria, Cushing's syndrome) or of gentamicin sulfate (ototoxic and nephrotoxic effects, which may be particularly dangerous in renal impairment).

Single overdoses of gentamicin have not led to overdose symptoms. However, excessive or prolonged use of gentamicin may result in overgrowth of antibiotic-resistant microorganisms.

Treatment. Initiate appropriate symptomatic therapy. Symptoms of acute hypercortisolism are usually reversible. If necessary, correct electrolyte imbalances. 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 therapy.

Adverse reactions.

Skin and subcutaneous tissue disorders.

Acne, steroid purpura, epidermal growth suppression, subcutaneous atrophy, folliculitis, erythema, hypertrichosis, secondary infection, urticaria or maculopapular rash, allergic contact dermatitis, miliaria, pruritus, burning sensation, irritation or exacerbation of pre-existing lesions, dry skin, skin maceration, stinging, skin irritation, skin dryness, scaling, focal desquamation, depigmentation or hyperpigmentation, skin discoloration, dilation of small superficial blood vessels, rosacea-like (perioral) dermatitis, redness, skin atrophy and striae when the product is used longer than recommended. Application to facial skin may cause perioral dermatitis.

Vascular disorders.

Prolonged use beyond the recommended duration may lead to dilatation of small blood vessels (telangiectasia).

Aural disorders.

Application to mucous membranes or large areas of skin, especially damaged skin, or under occlusive dressing, may cause ototoxic effects due to the presence of gentamicin sulfate in the ointment.

Endocrine system disorders.

Signs of hypercortisolism. Prolonged use of the ointment on large areas of skin or under occlusive dressing, or in children, taking into account the increased absorption of betamethasone dipropionate, may result in significant systemic corticosteroid effects, manifested as edema, arterial hypertension, decreased immunity, growth and developmental suppression in children, hyperglycemia, glucosuria, and development of Cushing's syndrome.

Eye disorders.

Topical application to the eyelid skin may occasionally lead to the development of glaucoma or accelerated progression of cataract.

Immune system disorders.

Hypersensitivity to corticosteroids may occur; in such cases, the use of the product must be discontinued immediately.

Renal and urinary disorders.

Application to large areas of skin, especially damaged skin, or under occlusive dressing may cause nephrotoxic effects due to the presence of gentamicin sulfate in the ointment.

Infections and infestations.

Secondary infections.

Belogent ointment is generally well tolerated. In very rare cases, skin irritation may occur, possibly related to individual hypersensitivity to gentamicin.

Local application of gentamicin may delay wound healing. In addition, topical use of gentamicin may occasionally cause ototoxicity, vestibular toxicity, and nephrotoxicity, particularly with repeated application to large wounds.

Cases of blurred vision (see also section "Special precautions for use") have been reported with corticosteroid use (frequency unknown).

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after marketing authorization. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.

Shelf life.

4 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 15 g or 30 g of ointment in a tube, 1 tube per cardboard box.

Prescription category.

Prescription only.

Manufacturer.

Belupo, Pharmaceuticals and Cosmetics, d.d.

Manufacturer's name and address.

Danicica 5, 48000 Koprivnica, Croatia.