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ratio * -Mometasone
*Trade-Mark used under license from ratiopharm GmbH ratiopharm Inc. Date of Preparation: 17800, rue Lapointe September 22, 2003 Mirabel, Quebec J7J 1P3 Control # 079660
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ratio *-Mometasone Mometasone Furoate 0.1% Ointment USP
Topical Corticosteroid
is a medium potency topical corticosteroid. Topical corticosteroids are synthetic derivatives of cortisone which are effective when applied locally to control many types of inflammatory, allergic and pruritic dermatoses. Modifications to the chemical structure such as fluorination, generally enhances both anti-inflammatory activity and increases the likelihood of adverse effects. The mechanism of anti-inflammatory activity of topical corticosteroids is generally unclear. However, corticosteroids are thought to induce phospholipase A2 inhibitor proteins, preventing arachidonic acid release and the biosynthesis of potent mediators of inflammation. Topical corticosteroids are primarily effective because of their anti-inflammatory, anti-pruritic and vasoconstrictive actions.
While the mechanism of the anti-inflammatory effect is unclear, it is recognized that there is a correlation between the therapeutic anti-inflammatory activity of corticosteroids and their vasoconstrictor potencies. Vasoconstrictor assays have therefore been used to compare and predict the relative therapeutic potencies of this class of compounds, which are applied topically and are not absorbed into the blood stream. In a comparative bioequivalence study between ratio *-Mometasone 0.1% Ointment and the Canadian reference product, the relative potency of each product was measured using a ChromaMeter. This device measures the degree of local vasoconstrictor response by measuring the degree of skin blanching produced by each drug. The following table reveals the results of the skin blanching measurements. Both products demonstrated comparable vasoconstrictor (therapeutic) activity.
Test Reference: Ratio 90% Confidence Interval 2
| Evaluation | N | ratio *-Mometasone 0.1% Ointment (ratiopharm inc.) | Elocom 0.1% Ointment (Schering Canada) | (%) 1 | Lower (%) | Upper (%) |
| ChromaMeter Reading (Skin blanching) | 38 | 13 | 13.3 | 98 | 88 | 108.5 |
1: Ratio percent calculated as Test/Reference x 100 2: Confidence interval on the ratio
ratio *-Mometasone
0.1% Ointment is indicated for relief of the inflammatory and pruritic manifestations of corticosteroid responsive dermatoses such as psoriasis and atopic dermatitis.
0.1% Ointment is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.
0.1% Ointment should not be used in bacterial/fungal skin infections, tuberculosis of the skin, syphilitic skin infections, chicken pox, eruptions following vaccinations and viral diseases of the skin in general.
0.1% Ointment is not for ophthalmic use.
When used under occlusive dressing, over extensive areas, or on the face, scalp, axillae and scrotum, sufficient absorption may occur giving rise to adrenal suppression and other systemic effects.
Systemic absorption of topical corticosteroids can produce reversible hypothalamic- pituitaryadrenal (HPA) axis suppression with the potential for glucorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycaemia and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids. Conditions which augment systemic absorption include application of the more potent steroids, use over a large surface areas, prolonged use and occlusive dressings. Patients receiving a large dose of potent topical steroids to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACT stimulation test or other recognized/validated test. 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 steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticoid insufficiency may occur requiring supplemental systemic corticosteroids. Occlusive dressings should not be applied if body temperature is elevated. To minimize systemic absorption when long-term therapy or large surface area for treatment is likely, periodic interruption of treatment or treatment of one area of the body at a time should be considered. Children may be more susceptible to systemic toxicity from equivalent doses due to larger skin surface to body mass ratios (see Precautions - Pediatric Use). Topical corticosteroids, particularly the more potent ones, should be used with caution on lesions close to the eye because systemic absorption may cause increased intra ocular pressure, glaucoma or cataracts. Prolonged use of topical corticosteroid preparations may produce striae or atrophy of the skin or sub-cutaneous tissue. Topical corticosteroids should be used with caution on lesions of the face, groin and axillae as these areas are more prone to atrophic changes than other areas of the body. Frequent observation is important if these areas are to be treated. If skin atrophy is observed, treatment should be discontinued. If irritation develops, ratio *-Mometasone 0.1% Ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis from corticosteroids is usually diagnosed by observing 'failure to heal' rather than clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing. Suitable precautions should be taken when using topical corticosteroids in patients with stasis dermatitis and other skin diseases with impaired circulation. If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favourable response does not occur promptly, use of ratio *-Mometasone 0.1% Ointment should be discontinued until the infection has been adequately controlled. Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.
Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage. ratio *-Mometasone 0.1% Ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, particularly in the first trimester of pregnancy. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for hydroadrenalism.
Systemically administered corticosteroids are secreted into human milk and could suppress growth, interfere with endogenous corticosteroid production or cause untoward effects. Caution should be exercised when ratio *-Mometasone 0.1% Ointment is administered to a nursing mother.
Safely and effectiveness of mometasone furoate in children and infants have not been established. Because of the higher ratio of skin surface area to body mass, children are at a greater risk than adults for HPA axis suppression when treated with topical corticosteroids. They are also at greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing's syndrome while on treatment. Adverse effect including striae have been reported with use of topical corticosteroids in infants and children. HPA axis suppression, Cushing's syndrome and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include: linear growth retardation, delayed weight gain, low plasma cortisol levels and absence of response to ACT stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches and bilateral papilloedema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.
Suitable precautions should be taken in using topical glucocorticoids in patients with impaired circulation suffering from stasis dermatitis and other skin diseases.
Long-term animals studies have been performed to evaluate carcinogenic potential of mometasone furoate (see TOXICOLOGY). Mometasone furoate was nonmutagenic in the mouse lymphoma assay and the salmonella/mammalian microsome bioassay, and was classified as negative in the mouse bone marrow erythrocyte micronucleus assay. A test in Chinese hamster ovary cells was inconclusive whereas a similar test measuring chromosomal aberration frequencies using rat liver S9 fraction was negative (see TOXICOLOGY). Mometasone furoate was tested for effects on reproduction. Dermal teratology studies demonstrated no unusual effects on the course of pregnancy or on embryo and fetal viability (see TOXICOLOGY).
The following local adverse reactions have been reported with mometasone furoate ointment: During clinical studies in 812 patients: burning - 13, pruritus - 8, skin atrophy - 8, tingling/stinging - 7, and furunculosis -3. The overall incidence of side effects was 4.9%, i.e., 40 of 812 subjects reported treatment-related adverse experiences. Side effects were mild to moderate and were those typically associated with topical corticosteroid formulations after seven days of treatment. No systemic treatment-related adverse experiences were seen. The following additional local adverse reactions have been reported with topical corticosteroids and may occur frequently with use of occlusive dressings. These reactions are listed in decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria. In addition, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction or discontinuation of potent topical corticosteroid products. Adrenal suppression has also been reported following topical corticosteroid therapy. Posterior subcapsular cataracts have been reported following systemic use of corticosteroids.
Topically applied ratio *-Mometasone 0.1% Ointment can be absorbed systemically. Percutaneous absorption is enhanced when large amounts of corticosteroids are applied, when used under occlusive dressing or when used chronically. Toxic effects of hypercorticism and adrenal suppression may appear. Should toxic effects occur, the dosage of mometasone furoate should be discontinued slowly, consistent with accepted procedures for discontinuation of chronic steroid therapy. The restoration of hypothalamic-pituitary axis may be slow; during periods of pronounced physical stress (severe infections, trauma, surgery); a supplement with systemic steroids may need to be considered. Toxic effect may include ecchymosis of skin, peptic ulceration, hypertension, aggravation of infection, hirsutism, acne, edema and muscle weakness due to protein depletion. Treatment of a patient with systemic toxic manifestations consists of assuring and maintaining a patent airway and supporting ventilation using oxygen and assisted or controlled respiration as required. This usually will be sufficient in the management of most reactions. Should circulatory depression occur, vasopressors and intravenous fluids may be used. Should a convulsion persist despite oxygen therapy, small increments of ultra-short acting barbiturate (pentobarbital or secobarbital) may be given intravenously. Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions.
Apply a thin film of ratio *-Mometasone 0.1% Ointment to affected areas of skin once daily. Rub in gently and completely. Therapy should be limited to 1 -2 weeks. If a symptomatic response is not noted within a few days to a week, the local applications of corticosteroid should be discontinued and the patient re-evaluated. Therapy should be discontinued as soon as lesions heal. Safely and effectiveness of mometasone furoate in children and infants have not been established.
0.1% Ointment should not be used with occlusive dressing unless directed by a physician.
0.1% Ointment is not recommended for children under 2 years of age.
mometasone furoate
9,21-dichloro-ll$,17-dihydroxy-16"-methyl-pregna
-1,4-diene-3,20-dione 17-(2-furoate)
Cl O O
H CH3 O
HO O
H
CH3
Cl H
O
Molecular formula: C27H30Cl206
521.43
Mometasone furoate is a white to off-white powder practically insoluble in water, slightly soluble in octanol, and moderately soluble in ethyl alcohol.
0.1% Ointment
each gram contains 1 mg of mometasone furoate in a base of white wax and white petrolatum. Other constituents are hexylene glycol and propylene glycol monostearate.
0.1% Ointment is supplied in 15 g tubes, boxes of one.
0.1% Ointment is stored at room temperature, between 15 to 30degC.