Triacutan®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRICUTAN® (TRIACUTAN)

Composition:

Active substances: betamethasone, clotrimazole, gentamicin;

1 g of the ointment contains: betamethasone dipropionate equivalent to 100% substance 0.64 mg, gentamicin sulfate equivalent to gentamicin 1 mg, clotrimazole equivalent to 100% substance 10 mg;

Excipients: phenoxyethanol, octyldodecanol, mineral oil, white soft paraffin.

Pharmaceutical form. Ointment.

Main physicochemical characteristics: white or almost white ointment.

Pharmacotherapeutic group. Corticosteroids for dermatological use. Corticosteroids in combination with antibiotics. Betamethasone and antibiotics.

ATC code D07CC01.

Pharmacological properties.

Mechanism of action.

Triakutan® combines three actions: the anti-inflammatory effect of betamethasone dipropionate, the antibacterial activity of gentamicin sulfate, and the antifungal effect of clotrimazole.

Pharmacodynamics.

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

Gentamicin is an aminoglycoside antibiotic 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 efficacy. Gentamicin is ineffective against most anaerobic bacteria, fungi, and viruses. Gentamicin has minimal activity against streptococci.

Resistance to gentamicin may develop in both gram-negative and gram-positive bacteria.

Clotrimazole is a synthetic antifungal agent belonging to the imidazole derivatives. Its spectrum of activity includes various fungi pathogenic for humans and animals. Clotrimazole exerts 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 species (including Candida albicans). Based on current knowledge, the antifungal action of clotrimazole is attributed to inhibition of ergosterol synthesis. Ergosterol is a vital 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 penetration depends on the site of application, skin condition, pharmaceutical formulation used, patient age, and method of administration.

Gentamicin

Systemic absorption can be disregarded when gentamicin is applied to intact skin. However, increased transdermal absorption should be considered in cases of compromised stratum corneum, inflammatory skin conditions, or when used under occlusive dressings or over large skin areas.

Clotrimazole

After topical application, systemic absorption is low, with most of the clotrimazole remaining in the stratum corneum. Concentrations observed 6 hours after application of 1% radiolabeled clotrimazole on intact and acutely inflamed skin were as follows: stratum corneum – 100 mcg/cm³, dermal 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 application of corticosteroids include skin infections [viral, bacterial (including tuberculosis) and fungal origin], skin reactions following vaccination, skin ulcers and acne. It is not recommended to apply the ointment in the presence 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 applying the ointment to the genital area and around the anal opening, the presence of soft paraffin (an excipient in the drug formulation) may reduce the tensile strength of latex condoms, thereby decreasing their reliability during use.

Clotrimazole, when applied topically, 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.

Triakutan® is not intended for ophthalmic use.

If skin irritation or signs of hypersensitivity develop during treatment with Triakutan® ointment, the drug should be discontinued and appropriate therapy should be initiated.

With topical application, systemic absorption of active ingredients may be increased when the drug is applied over large skin areas, with prolonged use, or to damaged skin. In such cases, adverse effects associated with systemic administration of the active substances 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 possible cross-allergic reactions with other aminoglycoside antibiotics.

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

Use of the drug in high doses, over large body surface areas, under occlusive dressings, or use of potent or very potent corticosteroids should be performed only under regular medical supervision—particularly with regard to suppression of endogenous corticosteroid production and possible metabolic effects.

Application of the drug 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, treatment duration should not exceed 1 week.

Corticosteroids may mask symptoms of an allergic reaction to one of the components of the drug. Patients should be instructed to use the drug only for personal treatment of their diagnosed skin condition and not to pass it on to others.

When systemic and topical corticosteroids (including intranasal, inhaled, and intraocular administration) are used, visual disturbances may occur. If symptoms such as blurred vision or other visual disturbances occur, the patient should undergo an ophthalmologic 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 than adult patients, due to a higher skin surface area to body mass 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

Animal studies have demonstrated teratogenic effects of topical corticosteroids. There are no adequate data on the use of these agents during pregnancy in humans.

Aminoglycosides cross the placental barrier and may harm 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. Data on the use of clotrimazole in pregnant women are also limited.

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

Triakutan® should be used only if clearly needed.

Triakutan® should not be used in large doses, over large skin areas, or for prolonged periods.

Lactation

It is unknown whether gentamicin, clotrimazole, or corticosteroids, when applied topically, can pass into breast milk. However, systemic corticosteroids are known to be excreted in breast milk.

Triakutan® should not be applied to the breasts during breastfeeding.

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

Method of Administration and Dosage.

For adults, apply Triakutan® thinly to the entire affected area and the adjacent area of intact skin twice daily, in the morning and evening, and rub in gently. The duration of treatment depends on the patient's clinical response to therapy, as well as clinical and microbiological findings.

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

Children.

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

Overdose.

Symptoms. With prolonged or excessive use of topical glucocorticosteroids, suppression of the hypothalamic-pituitary-adrenal system may occur, leading to secondary adrenal insufficiency and symptoms of hypercortisolism, 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. Appropriate symptomatic therapy should be administered. Symptoms of acute hypercortisolism are usually reversible. If necessary, correction of electrolyte imbalance should be performed. In cases of chronic toxic effects, gradual withdrawal of corticosteroids is recommended.

In case of overgrowth of resistant microorganisms, treatment with Triakutan® should be discontinued and appropriate antifungal or antibacterial therapy should be initiated.

Side effects

Initial treatment

Skin reactions

Rare: skin irritation, burning sensation, pruritus, dry skin, hypersensitivity reactions to one of the components of the medicinal product, and skin discoloration.

Application to large skin areas, under occlusive dressings and/or for prolonged periods

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

An increased risk of secondary infections should be considered due to reduced local resistance to infection.

Skin reactions

Localized skin changes such as skin atrophy (particularly on the face), telangiectasia, striae, stretch marks, subcutaneous hemorrhages, purpura, steroid-induced acneiform eruptions, rosacea-like/perioral dermatitis, hypertrichosis, and skin discoloration. It is unknown whether these skin discolorations are reversible.

Uncommon: contact sensitization to gentamicin.

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

Endocrine system

Suppression of endogenous corticosteroid synthesis, excessive adrenal gland activity with edema.

Metabolism

Emergence of latent diabetes mellitus.

Eye disorders

Blurred vision.

Ear, labyrinthine and renal disorders

When aminoglycoside antibiotics are used concomitantly systemically, combined ototoxicity/nephrotoxicity may occur during the use of Triakutan® ointment on large body surfaces or on areas of affected skin.

Musculoskeletal system

Osteoporosis, growth retardation (in children).

Shelf life. 2 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 an aluminum tube. 1 tube per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.