Each gram of Dermatril cream contains:

active ingredients: betamethasone [as dipropionate] – 0.5 mg(0.65mg), clotrimazole – 10 mg, gentamicin sulfate – 1 mg;
excipients: ceteareth-12, ceteareth-20, cetostearyl alcohol, liquid paraffin, propylene glycol, dimethicone, methylparaben, propylparaben,ethanol 96%, water purified.

Betamethasone [as dipropionate]: Pregna-1,4-diene-3,20-dione, 9-fluoro-11-hydroxy-16- methyl-17,21-bis(1-oxopropoxy)-, (11b,16b); 9-Fluoro-11b,17,21-trihydroxy-16b- methylpregna-1,4-diene-3,20-dione 17,21-dipropionate [5593-20-4].

Clotrimazole: 1H-Imidazole,1-[(2-chlorophenyl)diphenylmethyl]-; 1-(o-Chloro-a,adiphenylbenzyl)imidazole [23593-75-1].

Gentamicin sulfate: [1405-41-0].

Combined preparation for topical use; D07CC01.

Dermatril cream contains combinations of gentamicin sulfate, аn antibacterial agent, a clotrimazole, an antifungal agent, and betamethasone, a corticosteroid, for dermatologic use. Results of the well-controlled clinical studies using Dermatril cream suggest that this combination is more effective either the corticosteroid or anti-infective agent alone in infected dermatoses. This combinated drug more effective for improving the clinical severity of cutaneous candidiasis and Dermatril cream generally provides earlier relief of signs and symptoms of this infection.

Following topical application, Betamethasone produces anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Betamethasone decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Betamethasone have antimitotic activity on cutaneous fibroblasts and the epidermis.

Tachyphylaxis to the anti-inflammatory effects of the Betamethasone (as shown by vasoconstrictor assay) may occur with repeated application although the clinical importance of this effect is unknown. Following 3-times daily application to normal skin at the same site, diminished vasoconstrictor response may occur within 4–5 days. Withdrawal of the drug for 2–4 days restores response, although maximum vasoconstrictor response may be diminished; when application of the drug is reinstated, tachyphylaxis recurs.

Clotrimazole, an imidazole derivative, is a synthetic azole antifungal agent. Clotrimazole exerts its antifungal activity by altering cell membrane permeability, apparently by binding with phospholipids in the fungal cell membrane. In contrast to polyene antibiotics (e.g., amphotericin B), the action of Clotrimazole is less dependent on the sterol content of the cell membrane. As a result of alteration of permeability, the cell membrane is unable to function as a selective barrier, and potassium and other cellular constituents are lost.

Antimicrobial Action: Clotrimazole is an imidazole antifungal that interferes with ergosterol synthesis and therefore alters the permeability of the cell membrane of sensitive fungi. It is reported to be fungistatic at concentrations achieved clinically. Clotrimazole has a wide spectrum of antimicrobial activity including activity against Candida spp., Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes, and T. rubrum.

Resistance: the emergence of strains of Candida spp. resistant to Clotrimazole has become increasingly important, particularly in immunocompromised patients receiving long-term prophylaxis with clotrimazole. In addition to resistance in C. albicans, infections with C. dubliniensis, C. glabrata, and C. krusei, all of which may be less sensitive to Clotrimazole than C. albicans, have been noted in these patients,and secondary resistance of C. glabrata has been reported during clotrimazole therapy. Cross-resistance with other azoles and with amphotericin B has been reported.

Gentamicin is usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.

Spectrum: in general, Gentamicin is active against many aerobic gram-negative bacteria and some aerobic gram-positive bacteria. The drug is inactive against fungi, viruses, and most anaerobic bacteria. In vitro, Gentamicin concentrations of 1–8 mcg/ml inhibit most susceptible strains of Escherichia coli, Haemophilus influenzae, Moraxella lacunata, Neisseria, indole-positive and indole-negative Proteus, Pseudomonas (including most strains of Ps. aeruginosa), Staphylococcus aureus, S. epidermidis, and Serratia. However, different species and different strains of the same species may exhibit wide variations in susceptibility in vitro. In addition, in vitro susceptibility does not always correlate with in vivo activity. Gentamicin is only minimally active against streptococci.

Resistance: natural and acquired resistance to Gentamicin have been demonstrated in both gram-negative and gram-positive bacteria. Gentamicin resistance may be the result of decreased permeability of the bacterial cell wall, alterations in the ribosomal binding site, or the presence of a plasmid-mediated resistance factor which is acquired by conjugation. Plasmid-mediated resistance enables the resistant bacteria to enzymatically modify the drug by acetylation, phosphorylation, or adenylylation and can be transferred between organisms of the same or different species. Resistance to other aminoglycosides and several other anti-infectives (e.g., chloramphenicol, sulfonamides, tetracycline) may be transferred on the same plasmid. There is partial cross-resistance between Gentamicin and other aminoglycosides.

Percutaneous penetration of Betamethasone varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the corticosteroid, and by using different vehicles. Betamethasone apparently does not penetrate the dermis to a greater extent than does hydrocortisone. Following topical application of a Betamethasone to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation; however, absorption is markedly increased when the skin has lost its keratin layer and can be increased by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema). The drug is absorbed to a greater degree from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole. Even after washing the area being treated, prolonged absorption of the Betamethasone occurs, possibly because the drug is retained in the stratum corneum.

Betamethasone usually is metabolized in the liver and excreted by the kidneys.

Betamethasone crosses the placenta to varying degrees and may be distributed in small amounts into breast milk.

When applied topically Clotrimazole penetrates the epidermis but there is little if any systemic absorption.

Gentamicin sulfate is not usually absorbed following topical application to intact skin; however, the drug is readily absorbed through denuded areas of skin or skin that has lost the keratin layer as in wounds, burns, or ulcers.

Administration

Gently massage sufficient Dermatril cream into the affected and surrounding skin areas twice a day: in the morning and evening for two weeks in tinea cruris, tinea corporis and candidiasis, and for four weeks in tinea pedis. For treatment to be effective, Dermatril cream should be applied regularly.

Dermatril cream should not be used longer than 2 weeks in the treatment of tinea cruris, tinea corporis and candidiasis, and amounts greater than 45 g per week of Dermatril cream should not be used. If a patient with tinea cruris, tinea corporis and candidiasis shows no clinical improvement after one week of treatment with Dermatril cream, the diagnosis should be reviewed.

Dermatril cream should not be used longer than 4 weeks in the treatment of tinea pedis, and amounts greater than 45 g per week of Dermatril cream should not be used. If a patient with tinea pedis shows no clinical improvement after 3-4 weeks of treatment with Dermatril cream, the diagnosis should be reviewed.

Dermatril cream should not be used with occlusive dressings.

Patients using Dermatril cream should receive the following information and instructions

• This medication is to be used as directed by the physician and is not recommended for use longer than the prescribed time period. It is for external use only. Avoid contact with the eyes, the mouth, or intravaginally.
• This medication is to be used for the full prescribed treatment time, even though the symptoms may have improved. Notify the physician if there is no improvement after 1 week of treatment for tinea cruris or tinea corporis, or after 2 weeks for tinea pedis.
• This medication should only be used for the disorder for which it was prescribed.
• The treated skin areas should not be bandaged, covered, or wrapped so as to be occluded.
• Any signs of local adverse reactions should be reported to your physician.
• Patients should avoid sources of infection or reinfection.
• When using Dermatril cream in the groin area, patients should use the medication for two weeks only, and apply the cream sparingly. Patients should wear loose-fitting clothing. Notify the physician if the condition persists after 2 weeks.

Betamethasone

Systemic Effects

In general, topical application of Betamethasone to the skin does not provoke clinical evidence of systemic absorption. However, adverse systemic corticosteroid effects may occur when the drugs are used on large areas of the body, for prolonged periods of time, with an occlusive dressing, and/or in infants and children. Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria have occurred in some patients receiving topical corticosteroids. Recovery of HPA-axis function is generally prompt and complete following discontinuance of the drug. In some patients, signs and symptoms of steroid withdrawal may occur, necessitating supplemental systemic corticosteroid therapy. Reversible HPA-axis suppression has occurred following topical dosages as low as 7 g of Dermatril cream (3.5 mg of Betamethasone) daily in patients with psoriasis. Numbness of fingers has been reported in patients receiving topical clobetasol propionate preparations. In at least one patient receiving hydrocortisone buteprate cream, paresthesia has been reported.

Local Effects

Betamethasone may causes adverse dermatologic effects. Betamethasone should be used with caution on the face. Local adverse Betamethasone effects occur most frequently with occlusive dressings, especially with prolonged therapy, and may require discontinuing the occlusive dressing.

Betamethasone may causes atrophy of the epidermis, subcutaneous tissue, and dermal collagen and drying and cracking or tightening of the skin. Epidermal thinning, telangiectasia, increased fragility of cutaneous blood vessels, purpura, and atrophic striae may also occur. Other adverse dermatologic effects of Betamethasone include acne, acneiform eruption, vesiculation, irritation, pruritus, hypertrichosis, rosacea-like eruptions on the face, erythema, hyperesthesia, urticaria, perioral dermatitis, burning or stinging sensation, folliculitis, hypopigmentation, and alopecia. Skin ulceration has occurred in patients with impaired circulation who were treated with Betamethasone.

Adverse dermatologic effects of Betamethasone usually improve when the drug is discontinued but may persist for long periods; atrophic striae may be permanent. When prolonged (2 months or more) topical Betamethasone therapy is discontinued, pustular “rebound” may occur, especially on the face, perianal region, or genitals. Although improvement usually occurs spontaneously within a few weeks, some patients may require treatment with a systemic antibiotic (e.g., tetracycline) and a topical nonfluorinated corticosteroid (e.g., hydrocortisone) and/or sulfur.

In addition to the other adverse dermatologic effects of Betamethasone therapy, maceration of the skin and miliaria may occur, especially when occlusive dressings are used. Stripping of the epidermis and purpura have occurred with flurandrenolide tape dressings.

Topically applied Betamethasone are generally nonsensitizing, but allergic contact dermatitis may occur rarely. Allergic contact dermatitis associated with topical Betamethasone usually is diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical preparations that do not contain corticosteroids; such an observation should be corroborated with appropriate diagnostic patch testing.

Dermatologic infection may occur with topical Betamethasone therapy, particularly when an occlusive dressing is used. The anti-inflammatory activity of the drugs can also mask the manifestations of infection.

Clotrimazole

Although Clotrimazole is usually well tolerated when administered topically to the skin, blistering, erythema, edema, pruritus, burning, stinging, peeling, urticaria, skin fissures, and general irritation of the skin occasionally have occurred. If irritation or sensitization occurs following topical application of Dermatril cream, the drug should be discontinued.

Gentamicin

Gentamicin appears to have a low order of toxicity when applied to the skin; however, sensitization to the drug may occasionally result from topical application. In addition, Dermatril cream contains other ingredients such as parabens which may also cause allergic contact dermatitis. Local irritation including erythema and pruritus occur rarely following topical application of Gentamicin.

• Hypersensitivity to corticosteroids, gentamicin sulfate or imidazoles.
• Dermatril cream should not be used with occlusive dressings.
• Dematril cream contraindicated for children to 12 years of age.

If irritation or sensitization occurs following topical application of Dermatril cream, the drug should be discontinued. Use of Dermatril cream in the treatment of diaper dermatitis is not recommended.

General

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.

Conditions which augment systemic absorption include use over large surface areas, prolonged use, and use under occlusive dressings. Patients applying Dermatril cream to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid.

Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios.

If irritation develops, Dermatril cream should be discontinued and appropriate therapy instituted.

Pediatric Use

Pediatric patients may be more susceptible to topical corticosteroid-induced HPA-axis suppression and Cushing’s syndrome than mature individuals because of a greater skin surface area-to-body weight ratio. In open-label studies, adrenal suppression occurred in 14–17% of children 9–12 years of age, 23–32% of children 6–8 years of age, 29–38% of children 2–5 years of age, and 36–50% of infants 3 months to 1 year of age who received topical Betamethasone dipropionate cream for the treatment of atopic dermatitis. HPA-axis suppression, Cushing’s syndrome, and intracranial hypertension have occurred in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include retardation of linear growth, delayed weight gain, low plasma cortisol concentrations, and lack of response to corticotropin (ACTH) stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Topical corticosteroid therapy in children should be limited to the minimum amount necessary for therapeutic efficacy; chronic topical corticosteroid therapy may interfere with growth and development. Parents should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, since such garments may constitute occlusive dressings.

Geriatric Use

Adverse effects reporting for Dermatril cream in patients aged 65 and above includes reports of skin atrophy and extremely rare reports of skin ulceration. Caution should be exercised with the use of these corticosteroid containing topical products on thinning skin.

None well documented.

Safe use of Dermatril cream during pregnancy has not been established. Dermatril cream should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. The drug should not be used on extensive areas, in large amounts, or for prolonged periods in pregnant women.

It is not known whether active ingredients of Dermatril cream is distributed into milk. Dermatril cream should be used with caution in nursing women.

White, odorless cream.

15 g of cream is filled into aluminum tubeswhich are packed and inserted with the leaflet into cardboard boxes.

3 years. Do not use after the expiration date.

Store in a cool and dry place, out of the reach of children. Protect from light.

To be dispensed with prescription.