GENERIC NAME:Betamethasone (as17-valerate) micronized, Gentamicin (as sulphate), Tolnaftate, Iodochlorhydroxyquin. COMPOSITION: Each 1 gm contains: Active ingredient: Betamethasone(as17-valerate) micronized 0.5mg Gentamicin(as sulphate) 1mg Tolnaftate 10mg Iodochlorhydroxyquin 10mg : Excipients Chlorocresol, Monocetyl ether of polyetylene glycol, Cetostearyl alcohol, White petrolatum, Mineral oil FEU, Monobasic sodium phosphate, Distilled water. PHARMACEUTICAL FORM:Topical cream. PHARMACOLOGICAL ACTION: PHARMACODYNAMICS: Group pharmacotherapy: Potent corticosteroids, other combinations, Betamethasone. Quadriderm cream combines the corticosteroid valerate of betamethasone with the antibiotic bactericidal Gentamicin Sulphate, fungicide tolnaftate along with the agent antibacterial and the antifungal agent Clioquinol. Betamethasone valerate has anti-inflammatory activity and immunosuppressive and anti-proliferative properties. Corticosteroids in cutaneous use inhibit inflammatory reactions and allergic skin, as well as the reactions associated with hyper proliferation, leading to remission of objective symptoms (erythema, edema, and exudation) and relieve the discomfort (itching, burning sensation and pain). Anti-inflammatory effects are the result of inhibition of the formation, release and activity of inflammatory mediators. Thus, corticosteroids induce the anti-inflammatory protein lipocortin, which inhibits the enzyme phospholipase A2 and this synthesis of prostaglandins and lipoxygenase products. Corticosteroids also bind to glucocorticoid receptors (GRs) located in the cytoplasm, which move to the nucleus where there is a positive regulation of anti-inflammatory genes (such as lipocortin, neutral endopeptidase or inhibitors of Plasminogen activator). Corticosteroids produce vasoconstrictor action and their immunosuppressive properties cause reduction of the response of hypersensitivity reactions. Gentamicin is a bactericidal aminoglycoside antibiotic that acts by inhibiting the protein synthesis of the bacterium by binding with the 30S ribosomal subunit . Gentamicin is active in general against many Gram-negative aerobic bacteria and some gram-positive. It 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, hemophilic influenzae, Moraxella lacunata, Neisseria, indole-positive and indole-negative Proteus, Pseudomonas, Staphylococcus aureus, S. Epidermidis and Serratia. The production of natural and acquired resistance to gentamicin in Gram-negative and gram-positive bacteria is being demonstrated. The resistance can be due to alterations in the site of Ribosomal Junction, elaboration of enzymes by the bacterium mediated by plasmids or reduction of the permeability of the cellular wall of the bacterium. Clioquinol is an antibacterial and antifungal active ingredient. It is a halogenated 8- Hydroxy quinoline and is amebicide. In vitro, studies have shown that Clioquinol inhibits the growth of several organisms: fungi such as Microsporums, Trichophytes, Candida albicans and Gram-positive cocci such as staphylococci or Streptococcus. Tolnaftate is an effective topical antifungal in the treatment of superficial dermatophytes (ringworms); Candida is resistant. Its antifungal action mechanism is not specifically known, but it has been observed that tolnaftate distorts hyphae and prevents the growth of mycelium in sensitive fungi. Fungi typically sensitive to Tolnaftate include Microsporum canis, M. audouinii, Trichophyton Rubrun, T. Mentagrophytes and T. Tonsurans. Tolnaftate is not effective in treating deep fungal infections nor is it useful in the treatment of fungal infections of the scalp or nails. PHARMACOKINETICS: Topical corticosteroids may be absorbed into intact healthy skin. The extent of systemic absorption is determined by several factors including excipients in formulation, compound concentration, epidermal barrier integrity, long-term treatment, occlusive dressings; Inflammatory processes or other skin diseases increase percutaneous absorption of corticosteroids. The pharmacokinetic profile of topical glucocorticoids after penetration through the skin is similar to that of systemic glucocorticoids. Glucocorticoids binding to plasma proteins in varying degrees, are metabolized in the liver mainly, and are usually excreted via the kidneys; another minority route of excretion is by bile. The percutaneous absorption of the Betamethasone valerate in oily emulsion in healthy males with experimentally injured skin was evaluated. After 24 hours, 68.1 ± 6.9% was detected at a dose of 200 mg marked 3h. In urine and feces, 7.34-± 2.74% and 4.80 ± 0.76% of the dose in 72 hours were recovered respectively. The mean maximum concentrations of gentamicin were measured from 3.5-6.4 mg/L at 30-60 minutes after intramuscular administration of 1 mg of gentamicin/kg of body weight. The half-life is approx. 2 hours during the first 8-12 hours and then, the gentamicin is gradually released from the deep layers with a half-life of 100 to 150 hours. Excretion is only via the kidneys. The active is eliminated by unaltered and biologically active glomerular filtration. Clioquinol is absorbed systemically after topical application on the skin. In two studies in which Clioquinol was applied topical, formulated as cream or ointment, combined with a corticosteroid, it was estimated that about 2-3% of the dose is absorbed systemically. However, in another study in which the drug formulated as a 3% cream, uncombined, and covering the skin with an occlusive dressing for 12 hours, it was estimated that percutaneous absorption is about 40% in that period. The clioquinol is excreted renally. The pharmacokinetic profile of Tolnaftate is not well studied. In vitro studies, in which a 1% (V/V) tolnaftate solution was applied in polyethylene glycol 400 for 24 hours, revealed that the mean amount of tolnaftate that penetrated the epidermis and dermis was 2.60 ± 0.28 and 0.92 mg μg/cm2 ± 0.12/cm2 respectively. Pediatric population Children and adolescents have a higher skin area in relation to body weight and thinner skin, which can lead to absorption of greater amounts of the active ingredients compared to that of older patients. INDICATIONS: Local treatment of inflammatory manifestations of dermatosis that responds to corticosteroids in complicated cases with mixed infection caused by microorganisms sensitive to the components of the medication. The official recommendations on the proper use of anti-bacterial agents should be taken into account. DOSAGE AND ADMINISTRATION: Dosage • Adults and patients older than 12 years apply a thin layer of the cream on the affected area 2 times a day, in the morning and at night. The duration of the treatment should not exceed one or two weeks. If the medication is used on the face, the treatment should be as short as possible, one week at most. In tinea pedis cases, more prolonged treatments may be required (2 to 4 weeks). However, if no clinical improvement is obtained in 3 weeks, the diagnosis should be reviewed. Method of administration Cutaneous use. The cream must be applied by a soft massage with a thin layer covering the affected area, which was previously cleaned carefully. • Pediatric population Quadriderm cream is contraindicated for children under 2 years of age and is not recommended for children under 12 years old. CONTRAINDICATIONS: -Hypersensitivity to active ingredients, to other corticosteroids, to other aminoglycosides antibiotics, to iodine or to any of the excipients. -Presence of tuberculous or syphilitic processes. -Viral infections (for example, herpes or chickenpox) -Rosacea, perioral dermatitis, atrophic skin diseases and cutaneous vaccine reactions in the treated area. - Quadriderm cream should not be used on the eyes or on deep wounds. - Children under 2 years old. UNDESIRABLE EFFECTS: The incidence of local or systemic side effects increases with factors that increase percutaneous absorption. Adverse reactions reported with the use of Quadriderm cream, occasionally, are Erythema, pruritus and discoloration of the skin bleaching. Rash, irritation, hypersensitivity and dermatitis with the topical use of gentamicin sulphate, clioquinol and rarely with tolnaftate were discovered. Clioquinol used with occlusion and/or over large or eroded areas of skin may cause serum elevation of protein-bound iodine levels. Like other corticosteroids, with prolonged use, with large amounts, in the treatment of extensive areas, if occlusive dressings were used in children, there may be enough absorption to produce systemic side effects, especially if it is a powerful corticosteroid. The following reactions have been reported with the use of topical corticosteroids: local symptoms such as atrophy, dryness, burning, skin maceration, itching and erythema, at the place of application, Hematomas, Telangiectasia, folliculitis, stretch marks, miliaria, acneiform eruptions, contact dermatitis, Secondary infection, systemic effects of the corticosteroid due to its absorption as reversible suppression of hypothalamic-pituitary-adrenal axis with manifestations of Cushing syndrome (obesity on the trunk, rounded face, delayed healing, psychiatric symptoms, etc.), hyperglycemia, hypertension, edema, hyperthyroidism, benign intracranial hypertension, paresthesia, cataracts (subcapsular), hypertrichosis, Perioral Dermatitis and skin discoloration. Eye disorders with an un-known frequency: blurred vision. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
