Mometasone Furoate

Warnings and Precautions Ophthalmic Adverse Reactions ( 5.2 ) 05/2018

1 INDICATIONS AND USAGE Mometasone furoate cream, USP, 0.1% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 2 years of age or older. Mometasone furoate cream, USP, 0.1% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients ≥ 2 years of age. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin film of mometasone furoate cream USP, 0.1% to the affected skin areas once daily. Mometasone furoate cream USP, 0.1% may be used in pediatric patients 2 years of age or older. Since safety and efficacy of mometasone furoate cream USP, 0.1% have not been established in pediatric patients below 2 years of age; use in this age group is not recommended [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.4 )]. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Safety and efficacy of mometasone furoate cream USP, 0.1% in pediatric patients for more than 3 weeks of use have not been established. Mometasone furoate cream USP, 0.1% should not be used with occlusive dressings unless directed by a physician. Mometasone furoate cream USP, 0.1% should not be applied in the diaper area if the child still requires diapers or plastic pants, as these garments may constitute occlusive dressing. Mometasone furoate cream USP, 0.1% is for topical use only. It is not for oral, ophthalmic, or intravaginal use. Avoid use on the face, groin, or axillae. • Apply a thin film to the affected skin areas once daily. (2) • Discontinue therapy when control is achieved. (2) • If no improvement is seen within 2 weeks, reassess diagnosis. (2) • The safety and efficacy of mometasone furoate cream USP, 0.1% in pediatric patients for more than 3 weeks of use have not been established. (2) • Do not use with occlusive dressings unless directed by a physician. (2)

3 DOSAGE FORMS AND STRENGTHS Cream, 0.1%. Each gram of mometasone furoate cream, USP, 0.1% contains 1 mg of mometasone furoate in a white to off-white smooth and homogenous cream base. • Cream, 0.1%. ( 3 )

4 CONTRAINDICATIONS Mometasone furoate cream, USP, 0.1% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation. Mometasone furoate cream, USP, 0.1% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation. ( 4 )

6 ADVERSE REACTIONS Most common adverse reactions are: burning, pruritus, and skin atrophy. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In controlled clinical trials involving 319 subjects, the incidence of adverse reactions associated with the use of mometasone furoate cream, USP, 0.1% was 1.6%. Reported reactions included burning, pruritus, and skin atrophy. Reports of rosacea associated with the use of mometasone furoate cream, USP, 0.1% have also been received. In controlled clinical trials (n=74) involving pediatric subjects 2 to 12 years of age, the incidence of adverse experiences associated with the use of mometasone furoate cream, USP, 0.1% was approximately 7%. Reported reactions included stinging, pruritus, and furunculosis. The following adverse reactions were reported to be possibly or probably related to treatment with mometasone furoate cream, USP, 0.1% during clinical trials in 4% of 182 pediatric subjects 6 months to 2 years of age: decreased glucocorticoid levels, 2; paresthesia, 2; folliculitis, 1; moniliasis, 1; bacterial infection; 1 skin depigmentation, 1. The following signs of skin atrophy were also observed among 97 subjects treated with mometasone furoate cream, USP, 0.1% in a clinical trial: shininess, 4; telangiectasia, 1; loss of elasticity, 4; loss of normal skin markings, 4; thinness, 1; and bruising, 1. 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Postmarketing reports for local adverse reactions to topical corticosteroids include irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria. These adverse reactions may occur more frequently with the use of occlusive dressings. Postmarketing reports for ophthalmic adverse reactions to topical corticosteroids include blurred vision, cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy. To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted with mometasone furoate cream, USP, 0.1%.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Teratogenic Effects Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Therefore, mometasone furoate cream, USP, 0.1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. When administered to pregnant rats, rabbits, and mice, mometasone furoate increased fetal malformations. The doses that produced malformations also decreased fetal growth, as measured by lower fetal weights and/or delayed ossification. Mometasone furoate also caused dystocia and related complications when administered to rats during the end of pregnancy. In mice, mometasone furoate caused cleft palate at subcutaneous doses of 60 mcg/kg and above. Fetal survival was reduced at 180 mcg/kg. No toxicity was observed at 20 mcg/kg. (Doses of 20, 60, and 180 mcg/kg in the mouse are approximately 0.01, 0.02, and 0.05 times the estimated maximum clinical topical dose from mometasone furoate cream, USP, 0.1% on a mcg/m 2 basis.) In rats, mometasone furoate produced umbilical hernias at topical doses of 600 mcg/kg and above. A dose of 300 mcg/kg produced delays in ossification, but no malformations. (Doses of 300 and 600 mcg/kg in the rat are approximately 0.2 and 0.4 times the estimated maximum clinical topical dose from mometasone furoate cream, USP, 0.1% on a mcg/m 2 basis.) In rabbits, mometasone furoate caused multiple malformations (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at topical doses of 150 mcg/kg and above (approximately 0.2 times the estimated maximum clinical topical dose from mometasone furoate cream, USP, 0.1% on a mcg/m 2 basis). In an oral study, mometasone furoate increased resorptions and caused cleft palate and/or head malformations (hydrocephaly and domed head) at 700 mcg/kg. At 2800 mcg/kg most litters were aborted or resorbed. No toxicity was observed at 140 mcg/kg. (Doses at 140, 700, and 2800 mcg/kg in the rabbit are approximately 0.2, 0.9, and 3.6 times the estimated maximum clinical topical dose from mometasone furoate cream, USP, 0.1% on a mcg/m 2 basis.) When rats received subcutaneous doses of mometasone furoate throughout pregnancy or during the later stages of pregnancy, 15 mcg/kg caused prolonged and difficult labor and reduced the number of live births, birth weight, and early pup survival. Similar effects were not observed at 7.5 mcg/kg. (Doses of 7.5 and 15 mcg/kg in the rat are approximately 0.005 and 0.01 times the estimated maximum clinical topical dose from mometasone furoate cream, USP, 0.1% on a mcg/m 2 basis.) 8.3 Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when mometasone furoate cream, USP,0.1% is administered to a nursing woman. 8.4 Pediatric Use Mometasone furoate cream, USP, 0.1% may be used with caution in pediatric patients 2 years of age or older, although the safety and efficacy of drug use for longer than 3 weeks have not been established. Since safety and efficacy of mometasone furoate cream, USP, 0.1% have not been established in pediatric patients below 2 years of age, its use in this age group is not recommended. In a pediatric trial, 24 atopic dermatitis subjects, of whom 19 subjects were age 2 to 12 years, were treated with mometasone furoate cream, USP, 0.1% once daily. The majority of subjects cleared within 3 weeks. Mometason …

12.1 Mechanism of Action Like other topical corticosteroids, mometasone furoate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 .

11 DESCRIPTION Mometasone Furoate Cream USP, 0.1% contains mometasone furoate for topical use. Mometasone furoate is a synthetic corticosteroid with anti-inflammatory activity. Chemically, mometasone furoate is 9α, 21-dichloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17-(2-furoate), with the empirical formula C 27 H 30 Cl 2 O 6 , a molecular weight of 521.4 and the following structural formula: Mometasone furoate is a white to off-white powder practically insoluble in water, slightly soluble in octanol, and moderately soluble in ethyl alcohol. Each gram of Mometasone Furoate Cream USP, 0.1% contains 1 mg mometasone furoate in a white to off-white uniform cream base of aluminum starch octenylsuccinate, ceteareth-20, phosphoric acid, propylene glycol, propylene glycol stearate, purified water, stearyl alcohol, titanium dioxide, white petrolatum and white wax. Chemical Structure

10 OVERDOSAGE Topically applied mometasone furoate cream, USP, 0.1% can be absorbed in sufficient amounts to produce systemic effects [ see Warnings and Precautions ( 5.1 ) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Mometasone Furoate Cream USP, 0.1% is white to off-white in color and supplied in: NDC: 72162-1404-2: 15 g in a TUBE NDC: 72162-1404-4: 45 g in a TUBE Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid excessive heat. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504