Name of the medicinal product Diprosalic Qualitative and quantitative composition Diprosalic ointment: Each 1 gm contains 0.64mg betamethasone dipropionate micronized (equivalent to 0.5mg betamethasone, D90% > 10µm) and 30mg salicylic acid micronized (D90% > 60 micron). Physical characters: Ointment: Smooth, uniform, off white ointment free from lumps & foreign matter. Pharmaceutical form: ointment. INDICATIONS Diprosalic Ointment (Betamethasone Dipropionate and Salicylic Acid) are indicated for: Anti-inflammatory, antipruritic and keratolytic activity in the topical management of subacute and chronic hyperkeratotic and dry dermatoses responsive to corticosteroid therapy. Pediatrics Pediatrics: Based on the available data, the safety and efficacy of Diprosalic in pediatric patients have not been established. Geriatrics Geriatrics: There is no known evidence to suggest that use in the geriatric population is associated with differences in safety or effectiveness. CONTRAINDICATIONS Diprosalic is contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. • Viral diseases including vaccinia, varicella, herpes simplex. • Fungal infections. • Tuberculosis of the skin. DOSAGE AND ADMINISTRATION Dosing Considerations Diprosalic Ointment should not be used under occlusive dressing. Recommended Dose and Dosage Adjustment A thin film of Diprosalic Ointment should be applied to cover completely the affected area. The ointment should be massaged gently and thoroughly into the skin. The usual frequency of application is twice daily, in the morning and at night. For some patients, adequate maintenance may be achieved with less frequent application. If symptomatic response is not noted within a few days to a week, the local application of corticosteroids should be discontinued, and the patient re-evaluated. MISSED DOSE If a dose is missed, the patient can resume treatment with the next scheduled application. OVERDOSAGE Symptoms: Excessive or prolonged use of topical corticosteroids can suppress pituitary-adrenal function, resulting in secondary adrenal insufficiency, and produce manifestations of hypercorticism, including Cushing's disease. Excessive or prolonged use of topical preparations containing salicylic acid may cause symptoms of salicylism. Overdosage of salicylates may cause temporary hearing or visual disturbances, drowsiness and nausea. If this occurs, discontinue use until symptoms disappear. Treatment: Appropriate symptomatic treatment is indicated. Acute hypercorticoid symptoms are usually reversible. Treat electrolyte imbalance, if necessary. In case of chronic toxicity, slow withdrawal of corticosteroids is advised. Treatment of salicylism is symptomatic. Measures should be taken to rid the body rapidly of salicylate. Administer oral sodium bicarbonate to alkalinize the urine and force diuresis. WARNINGS AND PRECAUTIONS General Systemic absorption of topical corticosteroids or salicylic acid will be increased if extensive body surface areas are treated. Suitable precautions should be taken under these conditions or when long-term use is anticipated, particularly in infants and children. Patients should be advised to inform subsequent physicians of the prior use of corticosteroids. Occlusive dressings should not be used, as this may result in an increase in the systemic absorption of topical corticosteroids or salicylic acid. Driving and Operating Machinery Due caution should be exercised when driving or operating a vehicle or potentially dangerous machinery. Endocrine and Metabolism Application over extensive lesions may result in significant systemic absorption producing hypercorticism manifesting itself by adrenal suppression, moon facies, striae and suppression of growth. Genitourinary Avoid contact with mucous membranes. Keep Diprosalic Ointment away from the genital area and other orifices. Immune If an overt infection is present, appropriate antimicrobial treatment is indicated. Ophthalmologic These drugs should not be used in or near the eyes since Diprosalic is not formulated for ophthalmic use. Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Skin Avoid contact with mucous membranes. Suitable precautions should be taken in using topical corticosteroids in patients with stasis dermatitis and other skin diseases with impaired circulation. Prolonged use of corticosteroid preparations may produce striae or atrophy of the skin or subcutaneous tissue. If this occurs, treatment should be discontinued. If irritation, sensitization, excessive dryness, or unwanted scaling develops with the use of Diprosalic, treatment should be discontinued. Special Populations Pregnant Women Since safety of topical corticosteroid use in pregnant women has not been established, drugs of this class should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively in large amounts or for prolonged periods of time in pregnant patients. Breast-feeding Since it is not known whether topical administration of corticosteroids can result in sufficient systemic absorption to produce detectable quantities in breast milk, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatrics Based on the available data, the safety and efficacy of Diprosalic in pediatric patients have not been established. Any of the side effects that have been reported following systemic use of corticosteroids, including adrenal suppression, may also occur with topical corticosteroids, especially in infants and children. Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and to exogenous corticosteroid effects than mature patients because of a greater absorption due to a larger skin surface area to body weight ratio. Use of topical corticosteroids in children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with growth and development of children. HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intra-cranial hypertension include a bulging fontanelle, headaches, and bilateral papilledema. ADVERSE REACTIONS Adverse Reaction Overview The following local adverse skin reactions have been reported with the use of topical steroids; burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis. The following may occur more frequently with the use of occlusive dressings: maceration of the skin, secondary infection, skin atrophy, striae, miliaria. In addition, the salicylic acid component may cause local reddening of the skin, desquamation, pruritus and smarting. Continuous application of salicylic acid preparations to the skin may cause dermatitis. Hypersensitivity to salicylic acid may occur. Systemic adverse reactions, such as vision blurred, have also been reported with the use of topical corticosteroids. Reporting of suspected adverse reactions: The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Report any suspected adverse reactions via: Human Pharmacovigilance Department – Egyptian Pharmaceutical Vigilance Center (EPVC)- Egyptian Drug Authority (EDA). Website:www.mohp.gov.eg, e-mail: pv.followup@edaegypt.gov.eg or via sending e-mail to pv@memphis.com.eg ACTION AND CLINICAL PHARMACOLOGY Mechanism of Action Betamethasone dipropionate with salicylic acid combines the anti-inflammatory, antipruritic and vasoconstrictive activity of betamethasone dipropionate with the keratolytic effects of salicylic acid. Clinical Pharmacology Betamethasone dipropionate was compared with other fluorinated topical corticosteroids in the McKenzie/Stoughton vasoconstrictor test. In this test, betamethasone dipropionate was significantly more active (p<0.05) than fluocinolone acetonide, fluocortolone caproate plus fluocortolone, flumethasone pivalate and betamethasone valerate1. While the direct applicability of this vasoconstrictor test to clinical situations has not been conclusively demonstrated, the results showed betamethasone dipropionate to be active in a concentration of 0.000016%, the lowest concentration tested which showed activity. The keratolytic property of salicylic acid has been recognized for a long time. The percutaneous absorption of betamethasone-17, 21-dipropionate and salicylic acid was studied after one and two weeks of treatment of psoriasis and eczema. The treated areas varied between 8 and 41 dm2. No change in the plasma cortisol levels was detectable by the routinely used laboratory method. The treatment gave no detectable salicylate concentrations in plasma. Pharmaceutical particulars List of excipients Diprosalic ointment: White petrolaum, mineral oil. STORAGE, STABILITY AND DISPOSAL Store at temperature not exceeding 30°C.
