Tetraderm^® (Cream) Instructions for Use

Marketing Authorization Holder

Vertex, JSC (Russia)

Contact Information

Vertex JSC (Russia)

ATC Code

D07XC03 (Mometasone in combination with other drugs)

Dosage Form

Tetraderm®

Cream for external use: tubes 15 g or 30 g

Dosage Form, Packaging, and Composition

Cream for external use white or almost white, homogeneous.

Excipients: liquid paraffin (mineral oil) – 120 mg, cetearyl alcohol – 70 mg, propylene glycol – 50 mg, macrogol 6 cetearyl ether – 20 mg, macrogol 25 cetearyl ether – 20 mg, sodium dihydrogen phosphate dihydrate – 2 mg, purified water – up to 1 g.

15 g – aluminum tubes (1) with a polymer cap – cardboard packs.
30 g – aluminum tubes (1) with a polymer cap – cardboard packs.

Clinical-Pharmacological Group

A drug with anti-inflammatory, antibacterial, antifungal, and regenerating action for external use

Pharmacotherapeutic Group

Antibiotic-aminoglycoside + tissue repair stimulant + topical glucocorticosteroid + antifungal agent

Pharmacological Action

A combined drug for external use. It has anti-inflammatory, antipruritic, anti-exudative, antibacterial, antifungal (fungicidal), and regenerating action. The activity of the drug is due to the pharmacological properties of its components.

Gentamicin

A broad-spectrum antibiotic from the aminoglycoside group. It acts bactericidally and provides highly effective external treatment of primary and secondary bacterial skin infections. Active against gram-negative microorganisms: Pseudomonas aeruginosa, Enterobacter aerogenes, Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae; gram-positive microorganisms: Staphylococcus aureus (coagulase-positive, coagulase-negative and some penicillinase-producing strains).

Dexpanthenol

A derivative of pantothenic acid. Pantothenic acid, a water-soluble B vitamin (vitamin B₅), is a component of coenzyme A. It stimulates skin regeneration, normalizes cellular metabolism, accelerates mitosis and increases the strength of collagen fibers. An increased need for pantothenic acid is observed when the skin or tissues are damaged, and its deficiency can be compensated by the external application of dexpanthenol. It penetrates all layers of the skin. It has regenerating and weak anti-inflammatory effects.

Mometasone

A synthetic glucocorticosteroid (GCS) with local anti-inflammatory, antipruritic and anti-exudative effects. GCS induce the release of proteins that inhibit phospholipase A₂, collectively known as lipocortins, which control the biosynthesis of inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid.

Econazole

A synthetic imidazole derivative. It has antifungal and antibacterial action. It inhibits the biosynthesis of ergosterol, which regulates the permeability of the microorganism’s cell wall. It dissolves easily in lipids and penetrates tissues well. Active against dermatophytes Trichophyton, Microsporum, Epidermophyton, yeast-like fungi of the genus Candida, Corynebacterium minutissimum, as well as Malassezia furfur (Pityrosporum orbiculare), which causes pityriasis versicolor, and some gram-positive bacteria (streptococci, staphylococci).

Pharmacokinetics

Gentamicin

When applied externally, it is absorbed in insignificant amounts. Due to low absorption, it practically does not have systemic effects.

Dexpanthenol

When applied externally, it is absorbed and converted into pantothenic acid, binds to plasma proteins. Pantothenic acid is not metabolized in the body and is excreted unchanged by the kidneys.

Mometasone

The absorption of mometasone after external application is low. About 0.4% of the dose is detected in the systemic circulation 8 hours after a single application to intact skin (without an occlusive dressing). Absorption increases with inflammation and skin damage. Mometasone is intensively metabolized in the liver. It is excreted mainly by the kidneys and in small amounts with bile.

Econazole

When applied externally, econazole penetrates all layers of the skin and the nail plate. Therapeutic concentrations are achieved in the stratum corneum and other layers of the epidermis, as well as in the dermis. Systemic absorption is negligible when applied to the skin. Less than 1% of the applied dose is excreted through the intestines and by the kidneys.

Indications

Treatment of dermatoses of inflammatory origin with concomitant bacterial and mycotic infection or with a high probability of secondary infection

• Simple and allergic dermatitis;
• Atopic dermatitis;
• Eczema;
• Dermatomycoses (dermatophytosis, candidiasis, pityriasis versicolor), especially when localized in the groin area and large skin folds;
• Simple chronic lichen.

ICD codes

Dosage Regimen

The drug is used externally. The cream is applied in a thin layer to the affected areas of the skin, gently rubbing in, 2 times/day until a positive clinical result is achieved.

The duration of treatment is individual, depends on the size, location of the lesion and the severity of the disease and is usually 1-2 weeks. For dermatomycosis of the feet, the average duration of treatment is 2-4 weeks. It is not recommended to use Tetraderm^® for more than 4 weeks.

If improvement does not occur after treatment or new symptoms appear, the patient should consult a doctor. The drug should be used only according to the method of application and in the doses indicated in the instructions. If necessary, the patient should consult a doctor before using the drug.

Adverse Reactions

Classification of the frequency of adverse effects according to WHO recommendations: very common (≥1/10); common (from ≥1/100 to <1/10); uncommon (from ≥1/1000 to <1/100); rare (from ≥1/10000 to <1/1000); very rare (<1/10000, including isolated reports); frequency unknown (cannot be estimated from the available data).

Immune system disorders very rare – hypersensitivity reactions, angioedema.

Nervous system disorders very rare – burning sensation; frequency unknown – paresthesia.

Eye disorders frequency unknown – blurred vision.

Skin and subcutaneous tissue disorders common – itching, burning sensation; very rare – folliculitis, erythema, contact dermatitis, urticaria, skin peeling, perioral dermatitis, skin maceration, appearance of atrophic striae (stretch marks), telangiectasia; frequency unknown – secondary infection, furunculosis, irritation, dry skin, skin atrophy, pigmentation changes, hypertrichosis, acneiform dermatitis, local skin atrophy.

General disorders and administration site conditions: common – pain at the application site; uncommon – discomfort sensation, swelling.

When using external forms of GCS for a long time and/or when applied to large areas of the skin, or with the use of occlusive dressings, side effects characteristic of systemic GCS may occur, including adrenal insufficiency and Cushing’s syndrome.

Contraindications

• Hypersensitivity to dexpanthenol, econazole, gentamicin, mometasone or to any of the components of the drug;
• Post-vaccination skin reactions;
• Skin tuberculosis;
• Skin manifestations of syphilis;
• Chickenpox;
• Herpes simplex;
• Use in the area of open wounds, ulcers;
• Rosacea;
• Perioral dermatitis;
• Acne;
• Skin atrophy;
• Perianal and genital pruritus;
• Breastfeeding period;
• Children under 18 years of age (efficacy and safety have not been established).

With caution

• Pregnancy;
• Application to large areas of the skin;
• Long-term use;
• Use with impaired skin integrity;
• Use of occlusive dressings;
• Application to the skin of the face and intertriginous skin.

Use in Pregnancy and Lactation

Pregnancy

No controlled studies on the use of Tetraderm^® during pregnancy have been conducted. The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus. During pregnancy, Tetraderm^® should not be applied to large areas of the skin or for a long period of time.

Breastfeeding period

It is not known whether topical GCS are excreted in breast milk. In this regard, breastfeeding or the use of Tetraderm^® by a nursing mother should be discontinued.

Pediatric Use

The use of the drug is contraindicated under the age of 18 years (efficacy and safety have not been established).

Geriatric Use

The drug should be used with caution in elderly patients with existing atrophic skin changes.

Special Precautions

Tetraderm^® is not intended for use in ophthalmology. Avoid getting the drug into the eyes and the periorbital area. If the drug accidentally gets into the eyes, rinse them with clean water or saline and, if symptoms persist, consult a doctor.

The use of the drug with occlusive dressings is not recommended, except when necessary.

It should not be used to treat varicose trophic ulcers of the leg and open wounds.

Some areas of the body (groin folds, armpits and perianal area) are more at risk of developing striae, so the duration of application of the drug on these areas of the body should be limited.

If irritation or signs of hypersensitivity are noted when using Tetraderm^®, treatment should be discontinued and alternative therapy selected for the patient.

Any side effects encountered with the use of systemic GCS, including suppression of adrenal cortex function, may also be observed with the external use of GCS. Systemic absorption of topical GCS may increase with prolonged use, treatment of large body surfaces, or the use of occlusive dressings. In such cases, the development of side effects characteristic of systemic GCS is possible.

With systemic and local (including intranasal, inhalation and intraocular) use of GCS, visual disturbances may occur. If the patient has symptoms such as blurred vision or other visual disturbances, the patient should be recommended to consult an ophthalmologist to identify possible causes of visual impairment, including cataracts, glaucoma, or rare diseases, such as central serous chorioretinopathy (CSCR), which have been observed in a number of cases with systemic and local use of GCS.

It should be taken into account that GCS can change the manifestations of some skin diseases, which may complicate the diagnosis. In addition, the use of GCS can cause delayed wound healing.

The drug should be used with caution in individuals with existing atrophic skin changes, especially in elderly patients.

With long-term GCS therapy, sudden discontinuation of therapy may lead to the development of a rebound syndrome, manifested in the form of dermatitis with intense skin redness and a burning sensation. Therefore, after a long course of treatment, Tetraderm^® should be discontinued gradually, for example, by switching to an intermittent treatment regimen before completely stopping it.

Systemic absorption of gentamicin with external use may increase in case of application to large areas of the skin, especially with prolonged treatment or in the presence of skin damage. In such cases, there is a potential for gentamicin absorption and, accordingly, the development of symptoms of ototoxicity and other adverse events characteristic of gentamicin with its systemic use.

The development of cross-allergic reactions to antibiotics from the aminoglycoside group is possible.

With prolonged external use of gentamicin, growth of non-susceptible microflora may be observed. In this case, as well as with the development of irritation, hypersensitivity reactions and superinfection, treatment should be discontinued and appropriate therapy prescribed.

Effect on ability to drive vehicles and mechanisms

There are no data on the negative effect of Tetraderm^® on the ability to drive vehicles and mechanisms, as well as to perform other activities that require concentration and speed of psychomotor reactions. Patients should be warned about the possibility of blurred vision. If the described adverse event occurs, one should refrain from performing these activities.

Overdose

Symptoms

With long-term use of topical GCS in high doses, suppression of adrenal function with the development of secondary adrenal insufficiency and symptoms of hypercortisolism, including Cushing’s syndrome, is possible.

A single overdose of gentamicin is not accompanied by any symptoms. Long-term use or use in doses exceeding the recommended ones can lead to a significant growth of non-susceptible microflora, including fungal, in the lesion.

Overdose of econazole with external use does not lead to any symptoms.

Overdose of dexpanthenol with external use is not expected to cause any symptoms.

Treatment

Symptomatic therapy. Acute symptoms of hypercortisolism are usually reversible. If necessary, correction of water-electrolyte imbalance and discontinuation of the drug are indicated. In case of uncontrolled growth of non-susceptible microorganisms, treatment should be discontinued and appropriate therapy selected.

Drug Interactions

Studies of the interaction of the drug with other drugs have not been conducted, however, Tetraderm^® is not recommended to be used simultaneously with other drugs for external use.

Econazole, which is part of Tetraderm^®, is an inhibitor of CYP3A4/2C9. Due to its low systemic availability when applied to the skin, clinically significant interaction is unlikely. At the same time, cases of interaction with oral anticoagulants have been reported. Patients taking anticoagulants such as warfarin or acenocoumarol should exercise caution and also monitor the anticoagulant effect.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.