Triderm

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

Composition:

Active substances: 1 g of ointment contains: betamethasone dipropionate equivalent to betamethasone 0.5 mg, clotrimazole 10 mg and gentamicin sulfate equivalent to gentamicin 1 mg;

Excipients: mineral oil, white soft paraffin.

Pharmaceutical form. Ointment.

Main physicochemical properties: soft, homogeneous ointment of white to light yellow color, free from foreign particles.

Pharmacotherapeutic group.

Corticosteroids for dermatological use. Corticosteroids in combination with antibiotics. Betamethasone and antibiotics. ATC code D07CC01.

Pharmacological properties.

Mechanism of action.

Triderm® combines three actions: the anti-inflammatory effect of betamethasone dipropionate, the antibacterial activity of gentamicin sulfate, and the antifungal activity 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 Proteus strains, 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 activity against streptococci.

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

Clotrimazole is a synthetic antifungal agent of the imidazole derivatives group. Its spectrum of activity includes a range of fungi pathogenic for 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 species (including Candida albicans). Based on current knowledge, the antifungal action 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, or when applied under occlusive dressing or over large skin areas.

Clotrimazole

After topical 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, dermal 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 application of corticosteroids include skin infections [viral, bacterial (including tuberculosis), and fungal], 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).

Trikderm® is not indicated for use under occlusive dressings.

Trikderm® 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 anal region, the presence of soft paraffin or liquid paraffin (excipients in the 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.

TriDerma® is not intended for ophthalmic use.

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

With topical application, systemic absorption of active substances may be increased when the drug is applied to large skin areas, with prolonged use, or when applied to damaged skin areas. In such cases, adverse effects similar to those observed after 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.

In particular, cross-allergic reactions with other aminoglycoside antibiotics should be taken into account.

Prolonged topical use of antibiotics may sometimes lead to the growth of resistant microflora. In such cases, as well as in the development of superinfection, appropriate treatment should be initiated.

The use of the drug in high doses, over large body surface areas, or the use of potent or very potent corticosteroids should only be performed 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.

Prolonged continuous or incorrect use of topical corticosteroids may lead to rebound effects at the end of treatment (topical corticosteroid withdrawal syndrome). A severe form of rebound effect may manifest as dermatitis with intense redness, prickling, and burning sensations, which may spread beyond the initially treated area. The likelihood of such a reaction is higher when sensitive skin areas are treated, such as facial skin or skin in flexural areas of limbs. If initial symptoms return within a few days or weeks after successful treatment, withdrawal reaction should be suspected (see "Adverse Reactions"). Re-administration should be done cautiously, and in such cases, consultation with a specialist or consideration of alternative treatment options is advised.

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

Corticosteroids may mask symptoms of allergic reactions to one of the components of the drug. The patient should be instructed to use the drug 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 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 manifests as bulging fontanelle, headache, and bilateral optic disc swelling.

Use during pregnancy or breastfeeding.

Pregnancy

Animal studies have demonstrated teratogenic effects of topical corticosteroids. There are no adequate data on the use of this drug during human pregnancy.

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. There is insufficient data on the use of clotrimazole in pregnant women.

Animal studies did not demonstrate any risk of adverse effects of the drug on the fetus.

TriDerma® should be used only if clearly needed.

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

Lactation

It is unknown whether gentamicin, clotrimazole, and corticosteroids, when applied topically, can pass into breast milk. However, systemic corticosteroids have been detected in breast milk.

TriDerma® should not be applied to the mammary glands during breastfeeding.

Ability to affect reaction rate while driving or operating machinery.

The effect on the ability to drive vehicles or operate other machinery has not been studied.

Method of Administration and Dosage

For adults, apply Triderm® twice daily, in the morning and evening, as a thin layer to the entire affected area and the adjacent area of intact skin, and gently rub in.

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 may be required (2–4 weeks).

Children.

Triderm® is not recommended for use in children, as there is no experience with the use of this medication in this age group.

Overdose.

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

Acute overdose with 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 lesion.

Treatment. Appropriate symptomatic therapy should be administered. Symptoms of acute hypercorticism 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 Triderm® should be discontinued and appropriate antifungal or antibacterial therapy should be initiated.

Adverse Reactions

Initial treatment

Skin

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

Application to large skin areas, under occlusive dressings and/or for prolonged periods (see "Contraindications")

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

Secondary infections due to reduced local resistance should be considered as a potential risk.

Skin

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

Uncommon: Contact sensitization to gentamicin.

Frequency not known: Withdrawal syndrome — skin redness which may spread beyond the initially affected area, burning or prickling sensation, pruritus, skin peeling, exudation from vesicles (see "Special precautions for use").

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

Endocrine system

Suppression of endogenous corticosteroid synthesis, hyperactivity of adrenal glands with oedema.

Metabolism and nutrition

Development of latent diabetes mellitus.

Eye

Blurred vision.

Ear, labyrinthine and kidney disorders

When aminoglycoside antibiotics are used systemically concomitantly, cumulative ototoxicity/nephrotoxicity may occur during application of Triaderm® ointment to large body surface areas or to affected skin areas.

Musculoskeletal and connective tissue disorders

Osteoporosis, growth retardation (in children).

Shelf life. 3 years.

Storage conditions.

Store in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging.

15 g or 30 g in tubes. 1 tube per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Organon Heist bv, Belgium

Manufacturer's address and place of business.

Industriepark 30, 2220 Heist-op-den-Berg, Belgium