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1 INDICATIONS AND USAGE Mometasone Furoate Ointment is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients ≥ 2 years of age ( 1 ) Mometasone Furoate Ointment 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.

2 DOSAGE AND ADMINISTRATION 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) Do not use with occlusive dressings unless directed by a physician. (2) Apply a thin film of Mometasone Furoate Ointment to the affected skin areas once daily. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary [ see Warnings and Precautions(5.1)]. Do not use Mometasone Furoate Ointment with occlusive dressings unless directed by a physician. Do not apply Mometasone Furoate Ointment in the diaper area, as diapers or plastic pants constitute occlusive dressing. Avoid use on the face, groin, or axillae. Avoid contact with eyes. Wash hands after each application. Mometasone Furoate Ointment is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

4 CONTRAINDICATIONS Mometasone Furoate Ointment is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation. ( 4 ) Mometasone Furoate Ointment is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation.

5 WARNINGS AND PRECAUTIONS Reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment, Cushing's syndrome, and hyperglycemia may occur due to systemic absorption. Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. Modify use should HPA axis suppression develop. ( 5.1 , 8.4 ) Pediatric patients may be more susceptible to systemic toxicity. ( 5.1 , 8.4 ) May increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( 5.2 ) 5.1 Effects on Endocrine System Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or 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. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. This may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. In a study evaluating the effects of Mometasone Furoate Ointment on the HPA axis, 15 grams were applied twice daily for 7 days to 6 adult subjects with psoriasis or atopic dermatitis. The results show that the drug caused a slight lowering of adrenal corticosteroid secretion. If HPA axis suppression is documented, an attempt should be made to gradually 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 [see Use in Specific Populations (8.4)] . 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products, including the topical mometasone products [see Adverse reactions (6.2)] Avoid contact of Mometasone Furoate Ointment with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Allergic Contact Dermatitis If irritation develops, Mometasone Furoate Ointment should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. 5.4 Concomitant Skin Infections If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used.

diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. 5.4 Concomitant Skin Infections If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Mometasone Furoate Ointment should be discontinued until the infection has been adequately controlled.

6 ADVERSE REACTIONS Most common adverse reactions are burning, pruritus, skin atrophy, tingling/stinging and furunculosis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 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 812 subjects, the incidence of adverse reactions associated with the use of Mometasone Furoate Ointment was 4.8%. Reported reactions included burning, pruritus, skin atrophy, tingling/stinging, and furunculosis. Cases of rosacea associated with the use of Mometasone Furoate Ointment have been reported. The following adverse reactions were reported to be possibly or probably related to treatment with Mometasone Furoate Ointment during a clinical study in 5% of 63 pediatric subjects 6 months to 2 years of age: decreased glucocorticoid levels, 1; an unspecified skin disorder, 1; and a bacterial skin infection, 1. The following signs of skin atrophy were also observed among 63 subjects treated with Mometasone Furoate Ointment in a clinical trial: shininess, 4; telangiectasia, 1; loss of elasticity, 4; loss of normal skin markings, 4; and thinness,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, skin atrophy, 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.

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 Ointment 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 Ointment 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 Ointment 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 Ointment 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 of 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 Ointment 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 Ointment 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 Ointment is administered to a nursing woman.

toward 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 Ointment is administered to a nursing woman. 8.4 Pediatric Use Mometasone Furoate Ointment 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 Ointment have not been established in pediatric patients below 2 years of age, its use in this age group is not recommended. Mometasone Furoate Ointment caused HPA axis suppression in approximately 27% of pediatric subjects ages 6 to 23 months, who showed normal adrenal function by Cortrosyn test before starting treatment, and were treated for approximately 3 weeks over a mean body surface area of 39% (range 15%-99%). The criteria for suppression were: basal cortisol level of 5 mcg/dL, 30-minute post-stimulation level of 18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 3 subjects, using these same criteria. Long-term use of topical corticosteroids has not been studied in this population [see Clinical Pharmacology (12.2)]. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are, therefore, also at greater risk of glucocorticosteroid insufficiency during and/or after withdrawal of treatment. Pediatric patients may be more susceptible than adults to skin atrophy, including striae, when they are treated with topical corticosteroids. Pediatric patients applying topical corticosteroids to greater than 20% of body surface are at higher risk of HPA axis suppression. 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 intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Mometasone Furoate Ointment should not be used in the treatment of diaper dermatitis. 8.5 Geriatric Use Clinical trials of Mometasone Furoate Ointment included 310 subjects who were 65 years of age and over and 57 subjects who were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects. However, greater sensitivity of some older individuals cannot be ruled out.

8.1 Pregnancy Teratogenic Effects Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Therefore, Mometasone Furoate Ointment 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 Ointment 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 Ointment 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 Ointment 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 of 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 Ointment 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 Ointment 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 Ointment is administered to a nursing woman.

8.4 Pediatric Use Mometasone Furoate Ointment 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 Ointment have not been established in pediatric patients below 2 years of age, its use in this age group is not recommended. Mometasone Furoate Ointment caused HPA axis suppression in approximately 27% of pediatric subjects ages 6 to 23 months, who showed normal adrenal function by Cortrosyn test before starting treatment, and were treated for approximately 3 weeks over a mean body surface area of 39% (range 15%-99%). The criteria for suppression were: basal cortisol level of 5 mcg/dL, 30-minute post-stimulation level of 18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 3 subjects, using these same criteria. Long-term use of topical corticosteroids has not been studied in this population [see Clinical Pharmacology (12.2)]. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are, therefore, also at greater risk of glucocorticosteroid insufficiency during and/or after withdrawal of treatment. Pediatric patients may be more susceptible than adults to skin atrophy, including striae, when they are treated with topical corticosteroids. Pediatric patients applying topical corticosteroids to greater than 20% of body surface are at higher risk of HPA axis suppression. 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 intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Mometasone Furoate Ointment should not be used in the treatment of diaper dermatitis.

8.5 Geriatric Use Clinical trials of Mometasone Furoate Ointment included 310 subjects who were 65 years of age and over and 57 subjects who were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects. However, greater sensitivity of some older individuals cannot be ruled out.

11 DESCRIPTION Mometasone Furoate Ointment USP, 0.1% contains mometasone furoate for topical use. Mometasone furoate is a synthetic corticosteroid with anti-inflammatory activity. Chemically, mometasone furoate is 9a,21-dichloro-11b,17-dihydroxy-16a-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 Ointment USP, 0.1% contains 1 mg mometasone furoate in a white to off-white uniform ointment base of hexylene glycol, phosphoric acid, propylene glycol stearate (55% monoester), purified water, white wax, and white petrolatum. Structure

12 CLINICAL PHARMACOLOGY 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 12.2 Pharmacodynamics Studies performed with Mometasone Furoate Ointment indicate that it is in the medium range of potency as compared with other topical corticosteroids. In a study evaluating the effects of Mometasone Furoate Ointment on the HPA axis, 15 grams were applied twice daily for 7 days to 6 adult subjects with psoriasis or atopic dermatitis. The ointment was applied without occlusion to at least 30% of the body surface. The results showed that the drug caused a slight lowering of adrenal corticosteroid secretion [see Warnings and Precautions (5.1)] . Sixty-three pediatric subjects ages 6 to 23 months, with atopic dermatitis, were enrolled in an open-label HPA axis safety study. Mometasone Furoate Ointment was applied once daily for approximately 3 weeks over a mean body surface area of 39% (range 15% to 99%). In approximately 27% of subjects who showed normal adrenal function by Cortrosyn test before starting treatment, adrenal suppression was observed at the end of treatment with Mometasone Furoate Ointment. The criteria for suppression were: basal cortisol level of 5 mcg/dL, 30-minute post-stimulation level of 18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 3 subjects, using these same criteria [see Use in Specific Populations (8.4)] . 12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Studies in humans indicate that approximately 0.7% of the applied dose of Mometasone Furoate Ointment enters the circulation after 8 hours of contact on normal skin without occlusion. Inflammation and/or other disease processes in the skin may increase percutaneous absorption

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

12.2 Pharmacodynamics Studies performed with Mometasone Furoate Ointment indicate that it is in the medium range of potency as compared with other topical corticosteroids. In a study evaluating the effects of Mometasone Furoate Ointment on the HPA axis, 15 grams were applied twice daily for 7 days to 6 adult subjects with psoriasis or atopic dermatitis. The ointment was applied without occlusion to at least 30% of the body surface. The results showed that the drug caused a slight lowering of adrenal corticosteroid secretion [see Warnings and Precautions (5.1)] . Sixty-three pediatric subjects ages 6 to 23 months, with atopic dermatitis, were enrolled in an open-label HPA axis safety study. Mometasone Furoate Ointment was applied once daily for approximately 3 weeks over a mean body surface area of 39% (range 15% to 99%). In approximately 27% of subjects who showed normal adrenal function by Cortrosyn test before starting treatment, adrenal suppression was observed at the end of treatment with Mometasone Furoate Ointment. The criteria for suppression were: basal cortisol level of 5 mcg/dL, 30-minute post-stimulation level of 18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 3 subjects, using these same criteria [see Use in Specific Populations (8.4)] .

12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Studies in humans indicate that approximately 0.7% of the applied dose of Mometasone Furoate Ointment enters the circulation after 8 hours of contact on normal skin without occlusion. Inflammation and/or other disease processes in the skin may increase percutaneous absorption

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of Mometasone Furoate Ointment. Long-term carcinogenicity studies of mometasone furoate were conducted by the inhalation route in rats and mice. In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase of tumors at inhalation doses up to 67 mcg/kg (approximately 0.04 times the estimated maximum clinical topical dose from Mometasone Furoate Ointment on a mcg/m 2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 0.05 times the estimated maximum clinical topical dose from Mometasone Furoate Ointment on a mcg/m 2 basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced in male or female rats by subcutaneous doses up to 15 mcg/kg (approximately 0.01 times the estimated maximum clinical topical dose from Mometasone Furoate Ointment on a mcg/m 2 basis).

14 CLINICAL STUDIES The safety and efficacy of Mometasone Furoate Ointment, 0.1% for the treatment of corticosteroid-responsive dermatoses was demonstrated in two vehicle-controlled trials, one in psoriasis and one in atopic dermatitis. A total of 218 subjects received Mometasone Furoate Ointment (109 subjects) or the vehicle ointment applied once daily for 21 days.

16 HOW SUPPLIED/STORAGE AND HANDLING Mometasone Furoate Ointment USP is a white to off-white uniform ointment and supplied in 15-gram (NDC 13668-527-01) and 45-gram (NDC 13668-527-04) tubes; boxes of one. Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labelling (Patient Information). Inform patients of the following: Use Mometasone Furoate Ointment as directed by the physician. It is for external use only. Avoid contact with the eyes. Advise patients to report any visual symptoms to their healthcare providers. Do not use Mometasone Furoate Ointment on the face, underarms, or groin areas. Do not use Mometasone Furoate Ointment for any disorder other than that for which it was prescribed. Do not bandage or otherwise cover or wrap the treated skin area so as to be occlusive, unless directed by the physician. Report any signs of local adverse reactions to the physician. Advise patients not to use Mometasone Furoate Ointment in the treatment of diaper dermatitis. Do not apply Mometasone Furoate Ointment in the diaper area, as diapers or plastic pants may constitute occlusive dressing. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, contact the physician. Do not use other corticosteroid-containing products with Mometasone Furoate Ointment without first consulting with the physician.

Patient Information Mometasone Furoate (moe—MET—a—sone) Ointment 0.1 % Important information: Mometasone Furoate Ointment is for use on skin only. Do not use Mometasone Furoate Ointment in your eyes, mouth, or vagina. W hat is Mometasone Furoate Ointment ? • Mometasone Furoate Ointment is a prescription medicine used on the skin (topical) for the relief of redness, swelling, heat, pain (inflammation) and itching, caused by certain skin problems in people 2 years of age and older. • It is not known if Mometasone Furoate Ointment is safe and effective for use in children under 2 years of age. • Mometasone Furoate Ointment should not be used in children under 2 years of age. • It is not known if Mometasone Furoate Ointment is safe and effective for use in children longer than 3 weeks. Do not use Mometasone Furoate Ointment if you are allergic to mometasone furoate or any of the ingredients in Mometasone Furoate Ointment. See the end of this leaflet for a complete list of ingredients in Mometasone Furoate Ointment. Before using Mometasone Furoate Ointment , tell your healthcare provider about all your medical conditions, including if you: • have a skin infection at the site to be treated. You may also need medicine to treat the skin infection. • are pregnant or plan to become pregnant. It is not known if Mometasone Furoate Ointment will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if Mometasone Furoate Ointment passes into your breast milk. T el l your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin or scalp that contain corticosteroids. How should I use Mometasone Furoate Ointment ? • Use Mometasone Furoate Ointment exactly as your healthcare provider tells you to use it. • Apply a thin film of Mometasone Furoate Ointment to the affected skin area 1 time each day. • Use Mometasone Furoate Ointment until the affected skin area is improved. Tell your healthcare provider if the treated skin area does not get better after 2 weeks of treatment. • Do not bandage, cover, or wrap the treated skin area unless your healthcare provider tells you to. • Mometasone Furoate Ointment should not be used to treat diaper rash or redness. Do not apply Mometasone Furoate Ointment in the diaper area if wearing diapers or plastic pants. • Avoid using Mometasone Furoate Ointment on the face, groin, or underarms (armpits). • Wash your hands after applying Mometasone Furoate Ointment. W hat are the possible side effects of Mometasone Furoate Ointment ? Mometasone Furoate Ointment may cause serious side effects, including: • Mometasone Furoate Ointment ca n pass through your skin . Too much Mometasone Furoate Ointment passing through your skin can cause your adrenal glands to stop working properly. Your healthcare provider may do blood tests to check for adrenal gland problems. • Vision problems. Topical corticosteroids may increase your chance of developing vision problems such as cataract and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with Mometasone Furoate Ointment. • Skin problems.

s to check for adrenal gland problems. • Vision problems. Topical corticosteroids may increase your chance of developing vision problems such as cataract and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with Mometasone Furoate Ointment. • Skin problems. Skin problems may happen during treatment with Mometasone Furoate Ointment, including allergic reactions (contact dermatitis) and skin infections at the treatment site. Stop using Mometasone Furoate Ointment and tell your healthcare provider if you develop any skin reactions such as pain, tenderness, swelling, or other problems healing during treatment with Mometasone Furoate Ointment. T he most common side effects of Mometasone Furoate Ointment i nclude burning, itching, thinning of the skin (atrophy), tingling, stinging, and boils. These are not all the possible side effects of Mometasone Furoate Ointment. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA- 1088. How should I store Mometasone Furoate Ointment ? Store Mometasone Furoate Ointment at room temperature between 68°F to 77°F (20°C to 25°C). • Keep Mometasone Furoate Ointment a nd all medicines out of the reach of children. G e neral information about the safe and effective use of Mometasone Furoate Ointment . Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Mometasone Furoate Ointment for a condition for which it was not prescribed. Do not give Mometasone Furoate Ointment to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Mometasone Furoate Ointment that is written for health professionals. W hat are the ingredients in Mometasone Furoate Ointment ? A c tive ingredient: mometasone furoate I nactive ingredients: hexylene glycol, phosphoric acid, propylene glycol stearate (55% monoester), purified water, white wax, and white petrolatum. Manufactured by: Torrent Pharmaceuticals LTD. Pithampur, Dist. Dhar-454 775 (M.P.) India. Manufactured for: Torrent Pharma INC. Basking Ridge, NJ 07920. 8102444 Revised: 03/2026 Image

<table ID="ID120" width="0"><colgroup><col width="644"/></colgroup><tbody><tr><td styleCode="Botrule Lrule Rrule Toprule" align="center" valign="top"><content styleCode="bold"> Patient Information</content> <content styleCode="bold"> Mometasone Furoate (moe&#x2014;MET&#x2014;a&#x2014;sone)</content><content styleCode="bold"> Ointment 0.1 %</content></td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> Important information: </content><content styleCode="bold"> Mometasone Furoate Ointment is for use on skin only. </content> Do not use Mometasone Furoate Ointment in your eyes, mouth, or vagina.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> W</content><content styleCode="bold">hat is </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> ?</content> &#x2022; Mometasone Furoate Ointment is a prescription medicine used on the skin (topical) for the relief of redness, swelling, heat, pain (inflammation) and itching, caused by certain skin problems in people 2 years of age and older. &#x2022; It is not known if Mometasone Furoate Ointment is safe and effective for use in children under 2 years of age. &#x2022; Mometasone Furoate Ointment should not be used in children under 2 years of age. &#x2022; It is not known if Mometasone Furoate Ointment is safe and effective for use in children longer than 3 weeks.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> Do not use </content><content styleCode="bold"> Mometasone Furoate Ointment if you </content> are allergic to mometasone furoate or any of the ingredients in Mometasone Furoate Ointment. See the end of this leaflet for a complete list of ingredients in Mometasone Furoate Ointment.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> Before using </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> , tell your healthcare provider about all your medical conditions, including if you:</content> &#x2022; have a skin infection at the site to be treated. You may also need medicine to treat the skin infection. &#x2022; are pregnant or plan to become pregnant. It is not known if Mometasone Furoate Ointment will harm your unborn baby. &#x2022; are breastfeeding or plan to breastfeed. It is not known if Mometasone Furoate Ointment passes into your breast milk. <content styleCode="bold"> T</content><content styleCode="bold">el</content><content styleCode="bold">l your healthcare provider about all the medicines you take, </content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin or scalp that contain corticosteroids.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> How should I use </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> ?</content> &#x2022; Use Mometasone Furoate Ointment exactly as your healthcare provider tells you to use it. &#x2022; Apply a thin film of Mometasone Furoate Ointment to the affected skin area 1 time each day. &#x2022; Use Mometasone Furoate Ointment until the affected skin area is improved.

<content styleCode="bold"> ?</content> &#x2022; Use Mometasone Furoate Ointment exactly as your healthcare provider tells you to use it. &#x2022; Apply a thin film of Mometasone Furoate Ointment to the affected skin area 1 time each day. &#x2022; Use Mometasone Furoate Ointment until the affected skin area is improved. Tell your healthcare provider if the treated skin area does not get better after 2 weeks of treatment. &#x2022; Do not bandage, cover, or wrap the treated skin area unless your healthcare provider tells you to. &#x2022; Mometasone Furoate Ointment should not be used to treat diaper rash or redness. Do not apply Mometasone Furoate Ointment in the diaper area if wearing diapers or plastic pants. &#x2022; Avoid using Mometasone Furoate Ointment on the face, groin, or underarms (armpits). &#x2022; Wash your hands after applying Mometasone Furoate Ointment.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> W</content><content styleCode="bold">hat are the possible side effects of </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> ? </content><content styleCode="bold"> Mometasone Furoate Ointment </content><content styleCode="bold"> may cause serious side effects, including:</content> &#x2022; <content styleCode="bold"> Mometasone Furoate Ointment </content><content styleCode="bold"> ca</content><content styleCode="bold"> n pass through your skin</content> . Too much Mometasone Furoate Ointment passing through your skin can cause your adrenal glands to stop working properly. Your healthcare provider may do blood tests to check for adrenal gland problems. &#x2022; <content styleCode="bold"> Vision problems. </content> Topical corticosteroids may increase your chance of developing vision problems such as cataract and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with Mometasone Furoate Ointment. &#x2022; <content styleCode="bold"> Skin problems.</content> Skin problems may happen during treatment with Mometasone Furoate Ointment, including allergic reactions (contact dermatitis) and skin infections at the treatment site. Stop using Mometasone Furoate Ointment and tell your healthcare provider if you develop any skin reactions such as pain, tenderness, swelling, or other problems healing during treatment with Mometasone Furoate Ointment. <content styleCode="bold"> T</content><content styleCode="bold">he most common side effects of </content><content styleCode="bold"> Mometasone Furoate Ointment </content><content styleCode="bold"> i</content><content styleCode="bold"> nclude </content> burning, itching, thinning of the skin (atrophy), tingling, stinging, and boils. These are not all the possible side effects of Mometasone Furoate Ointment. Call your doctor for medical advice about side effects.

roate Ointment </content><content styleCode="bold"> i</content><content styleCode="bold"> nclude </content> burning, itching, thinning of the skin (atrophy), tingling, stinging, and boils. These are not all the possible side effects of Mometasone Furoate Ointment. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA- 1088.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> How should I store </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> ?</content> Store Mometasone Furoate Ointment at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top">&#x2022; <content styleCode="bold"> Keep </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> a</content><content styleCode="bold"> nd all medicines out of the reach of children.</content></td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><content styleCode="bold"> G</content><content styleCode="bold"> e</content><content styleCode="bold"> neral information about the safe and effective use of </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> .</content> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Mometasone Furoate Ointment for a condition for which it was not prescribed. Do not give Mometasone Furoate Ointment to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Mometasone Furoate Ointment that is written for health professionals.</td></tr><tr><td styleCode="Botrule Lrule Rrule" align="left" valign="top"><paragraph><content styleCode="bold"> W</content><content styleCode="bold"> hat are the ingredients in </content><content styleCode="bold"> Mometasone Furoate Ointment</content><content styleCode="bold"> ? </content> <content styleCode="bold">A</content><content styleCode="bold">c</content><content styleCode="bold">tive ingredient: </content> mometasone furoate <content styleCode="bold"> I</content><content styleCode="bold">nactive ingredients: </content> hexylene glycol, phosphoric acid, propylene glycol stearate (55% monoester), purified water, white wax, and white petrolatum. <renderMultiMedia referencedObject="IMGID1201"/> <content styleCode="bold"> Manufactured by: </content>Torrent Pharmaceuticals LTD. Pithampur, Dist. Dhar-454 775 (M.P.) India. <content styleCode="bold">Manufactured for: </content>Torrent Pharma INC. Basking Ridge, NJ 07920.</paragraph><paragraph>8102444 Revised: 03/2026</paragraph></td></tr></tbody></table>

1 INDICATIONS AND USAGE Mometasone furoate topical solution USP, 0.1% (lotion) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years of age or older. Mometasone furoate topical solution USP, 0.1% (lotion) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients ≥ 12 years of age. (1)

2 DOSAGE AND ADMINISTRATION Apply a few drops of mometasone furoate lotion to the affected skin areas once daily and massage lightly until it disappears. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary [ see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.4 ) ]. Do not use mometasone furoate lotion with occlusive dressings unless directed by a physician. Do not apply mometasone furoate lotion in the diaper area if the patient requires diapers or plastic pants, as these garments may constitute occlusive dressing. Mometasone furoate lotion is for topical use only. It is not for oral, ophthalmic, or intravaginal use. Avoid use on the face, groin, or axillae. Avoid contact with eyes. Wash hands after each application. • Apply a few drops to the affected skin areas once daily and massage lightly until it disappears. (2) • Discontinue therapy when control is achieved. (2) • If no improvement is seen within 2 weeks, reassess diagnosis. (2) • Do not use with occlusive dressings unless directed by a physician. (2

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

5 WARNINGS AND PRECAUTIONS • Reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment, Cushing's syndrome, and hyperglycemia may occur due to systemic absorption. Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. Modify use should HPA axis suppression develop. (5.1, 8.4) • Pediatric patients may be more susceptible to systemic toxicity. (5.1, 8.4) • May increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. (5.2) 5.1 Effects on Endocrine System Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. This may occur during treatment or 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. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of high potency steroids, large treatment surface areas, prolonged use, use of occlusive dressing, altered skin barrier, liver failure and young age. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. This may be done by using the adrenocorticotropic hormone (ACTH) stimulation test. In a study evaluating the effects of mometasone furoate lotion on the HPA axis, 15 mL were applied without occlusion twice daily (30 mL per day) for 7 days to 4 adult subjects with scalp and body psoriasis. At the end of treatment, the plasma cortisol levels for each of the 4 subjects remained within the normal range and changed little from baseline. If HPA axis suppression is documented, an attempt should be made to gradually 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 [ see Use in Specific Populations ( 8.4 ) ]. 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products, including the topical mometasone products [see Adverse Reactions ( 6.2 )]. Avoid contact of Mometasone furoate lotion with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Allergic Contact Dermatitis If irritation develops, mometasone furoate lotion should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing.

elops, mometasone furoate lotion should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation should be corroborated with appropriate diagnostic patch testing. 5.4 Concomitant Skin Infections If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of mometasone furoate lotion should be discontinued until the infection has been adequately controlled.

6 ADVERSE REACTIONS Most common adverse reactions included are acneiform reaction, burning, itching and folliculitis. (6) To report SUSPECTED ADVERSE REACTIONS, contact Encube Ethicals Private Limited, at-833-285-4151 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 clinical trials involving 209 subjects, the incidence of adverse reactions associated with the use of mometasone furoate lotion was 3%. Reported reactions included acneiform reaction, 2; burning, 4; and itching, 1. In an irritation/sensitization study involving 156 normal subjects, the incidence of folliculitis was 3% (4 subjects). The following adverse reactions were reported to be possibly or probably related to treatment with mometasone furoate lotion during a clinical trial in 14% of 65 pediatric subjects 6 months to 2 years of age: decreased glucocorticoid levels, 4; paresthesia, 2; dry mouth,1; an unspecified endocrine disorder, 1; pruritus, 1; and an unspecified skin disorder, 1. The following signs of skin atrophy were also observed among 65 subjects treated with mometasone furoate lotion in a clinical observed among 65 subjects treated with mometasone furoate lotion in a clinical trial: shininess, 4; telangiectasia, 2; loss of elasticity, 2; and loss of normal skin markings, 3. 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, skin atrophy, 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.

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 lotion 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 lotion 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 lotion 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 lotion 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 lotion 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 lotion 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 lotion is administered to a nursing woman. 8.4 Pediatric Use Since safety and efficacy of mometasone furoate lotion have not been established in pediatric patients below 12 years of age, its use in this age group is not recommended.

y drugs are excreted in human milk, caution should be exercised when mometasone furoate lotion is administered to a nursing woman. 8.4 Pediatric Use Since safety and efficacy of mometasone furoate lotion have not been established in pediatric patients below 12 years of age, its use in this age group is not recommended. Mometasone furoate lotion caused HPA axis suppression in approximately 29% of pediatric subjects ages 6 to 23 months, who showed normal adrenal function by Cortrosyn test before starting treatment, and were treated for approximately 3 weeks over a mean body surface area of 40% (range 16% to 90%). The criteria for suppression were: basal cortisol level of ≤5 mcg/dL, 30-minute poststimulation level of ≤18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 1 subject, using these same criteria. Long-term use of topical corticosteroids has not been studied in this population [see Clinical Pharmacology ( 12.2 )] . Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are, therefore, also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Pediatric patients may be more susceptible than adults to skin atrophy, including striae, when they are treated with topical corticosteroids. Pediatric patients applying topical corticosteroids to greater than 20% of body surface are at higher risk of HPA axis suppression. HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Mometasone furoate lotion should not be used in the treatment of diaper dermatitis. 8.5 Geriatric Use Clinical trials of mometasone furoate lotion did no include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range.

8.1 Pregnancy Teratogenic Effects Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Therefore, mometasone furoate lotion 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 lotion 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 lotion 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 lotion 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 lotion 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 lotion 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 lotion is administered to a nursing woman.

8.4 Pediatric Use Since safety and efficacy of mometasone furoate lotion have not been established in pediatric patients below 12 years of age, its use in this age group is not recommended. Mometasone furoate lotion caused HPA axis suppression in approximately 29% of pediatric subjects ages 6 to 23 months, who showed normal adrenal function by Cortrosyn test before starting treatment, and were treated for approximately 3 weeks over a mean body surface area of 40% (range 16% to 90%). The criteria for suppression were: basal cortisol level of ≤5 mcg/dL, 30-minute poststimulation level of ≤18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 1 subject, using these same criteria. Long-term use of topical corticosteroids has not been studied in this population [see Clinical Pharmacology ( 12.2 )] . Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are, therefore, also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Pediatric patients may be more susceptible than adults to skin atrophy, including striae, when they are treated with topical corticosteroids. Pediatric patients applying topical corticosteroids to greater than 20% of body surface are at higher risk of HPA axis suppression. HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Mometasone furoate lotion should not be used in the treatment of diaper dermatitis.

8.5 Geriatric Use Clinical trials of mometasone furoate lotion did no include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of the dosing range.

11 DESCRIPTION Mometasone furoate topical solution USP, 0.1% (lotion) contains mometasone furoate for topical use. Mometasone furoate is a synthetic corticosteroid with anti-inflammatory activity. Chemically, mometasone furoate is 9,21-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 Soluble in acetone and methylene chloride. Each gram of mometasone furoate topical solution USP, 0.1% (lotion) contains 1 mg mometasone furoate in a colorless, clear to light haziness lotion base of hydroxypropyl cellulose, isopropyl alcohol (40%), propylene glycol, purified water and sodium phosphate monobasic monohydrate. May also contain phosphoric acid used to adjust the pH to approximately 4.5. structure

12 CLINICAL PHARMACOLOGY 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 . 12.2 Pharmacodynamics Studies performed with mometasone furoate lotion indicate that it is in the medium range of potency as compared with other topical corticosteroids. In a study evaluating the effects of mometasone furoate lotion on the HPA axis, 15 mL were applied without occlusion twice daily (30 mL per day) for 7 days to 4 adult subjects with scalp and body psoriasis. At the end of treatment, the plasma cortisol levels for each of the 4 subjects remained within the normal range and changed little from baseline [ see Warnings and Precautions ( 5.1 ) ]. Sixty-five pediatric subjects ages 6 to 23 months, with atopic dermatitis, were enrolled in an open label, HPA axis safety trial. Mometasone furoate lotion was applied once daily for approximately 3 weeks over a mean body surface area of 40% (range 16%-90%). In approximately 29% of subjects who showed normal adrenal function by Cortrosyn test before starting treatment, adrenal suppression was observed at the end of treatment with mometasone furoate lotion. The criteria for suppression were: basal cortisol level of ≤5 mcg/dL, 30-minute poststimulation level of ≤18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 1 subject, using these same criteria [ see Use in Specific Populations ( 8.4 ) ]. 12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Studies in humans indicate that approximately 0.7% of the applied dose of mometasone furoate ointment enters the circulation after 8 hours of contact on normal skin without occlusion. A similar minimal degree of absorption of the corticosteroid from the lotion formulation would be anticipated. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

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 .

12.2 Pharmacodynamics Studies performed with mometasone furoate lotion indicate that it is in the medium range of potency as compared with other topical corticosteroids. In a study evaluating the effects of mometasone furoate lotion on the HPA axis, 15 mL were applied without occlusion twice daily (30 mL per day) for 7 days to 4 adult subjects with scalp and body psoriasis. At the end of treatment, the plasma cortisol levels for each of the 4 subjects remained within the normal range and changed little from baseline [ see Warnings and Precautions ( 5.1 ) ]. Sixty-five pediatric subjects ages 6 to 23 months, with atopic dermatitis, were enrolled in an open label, HPA axis safety trial. Mometasone furoate lotion was applied once daily for approximately 3 weeks over a mean body surface area of 40% (range 16%-90%). In approximately 29% of subjects who showed normal adrenal function by Cortrosyn test before starting treatment, adrenal suppression was observed at the end of treatment with mometasone furoate lotion. The criteria for suppression were: basal cortisol level of ≤5 mcg/dL, 30-minute poststimulation level of ≤18 mcg/dL, or an increase of <7 mcg/dL. Follow-up testing 2 to 4 weeks after stopping treatment, available for 8 of the subjects, demonstrated suppressed HPA axis function in 1 subject, using these same criteria [ see Use in Specific Populations ( 8.4 ) ].

12.3 Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Studies in humans indicate that approximately 0.7% of the applied dose of mometasone furoate ointment enters the circulation after 8 hours of contact on normal skin without occlusion. A similar minimal degree of absorption of the corticosteroid from the lotion formulation would be anticipated. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of mometasone furoate lotion. Long-term carcinogenicity studies of mometasone furoate were conducted by the inhalation route in rats and mice. In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase of tumors at inhalation doses up to 67 mcg/kg (approximately 0.04 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 0.05 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced in male or female rats by subcutaneous doses up to 15 mcg/kg (approximately 0.01 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential of mometasone furoate lotion. Long-term carcinogenicity studies of mometasone furoate were conducted by the inhalation route in rats and mice. In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase of tumors at inhalation doses up to 67 mcg/kg (approximately 0.04 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 0.05 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced in male or female rats by subcutaneous doses up to 15 mcg/kg (approximately 0.01 times the estimated maximum clinical topical dose from mometasone furoate lotion on a mcg/m 2 basis).

14 CLINICAL STUDIES The safety and efficacy of mometasone furoate lotion for the treatment of corticosteroid-responsive dermatoses was demonstrated in two vehicle controlled trials, one in scalp psoriasis and one in seborrheic dermatitis. A total of 405 subjects (age range: 12 to 95 years) received mometasone furoate lotion (205 subjects) or the vehicle lotion applied once daily for 21 days.

16 HOW SUPPLIED/STORAGE AND HANDLING Mometasone furoate topical solution USP, 0.1% (lotion) is colorless, clear to translucent and supplied in 30-mL (27.5 gram) (NDC 21922-072-21) and 60-mL (55 gram) (NDC 21922-072-01) bottles; boxes of one. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Inform patients of the following: • Use mometasone furoate lotion as directed by the physician. It is for external use only. • Avoid contact with the eyes. • Advise patients to report any visual symptoms to their healthcare providers. • Do not use mometasone furoate lotion on the face, underarms, or groin areas. • Do not use mometasone furoate lotion for any disorder other than that for which it was prescribed. • Do not bandage or otherwise cover or wrap the treated skin area so as to be occlusive, unless directed by the physician. • Report any signs of local adverse reactions to the physician. • Advise patients not to use mometasone furoate lotion in the treatment of diaper dermatitis. Do not apply mometasone furoate lotion in the diaper area, as diapers or plastic pants may constitute occlusive dressing. • Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, contact the physician. • Do not use other corticosteroid-containing products with mometasone furoate lotion without first consulting with the physician. Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, Goa - 403 404, India. Distributed by: Encube Ethicals, Inc. 200 Meredith Drive, Suite 202 Durham, NC 27713 USA Revised:12/2024

PATIENT INFORMATION Mometasone Furoat Topical Solution USP, 0.1% (lotion) (moe met' a sone fure' oh ate) Important information: Mometasone furoate lotion is for use on skin only. Do not use Mometasone furoate lotion in your eyes, mouth, or vagina. What is mometasone furoate lotion? • Mometasone furoate lotion is a prescription medicine used on the skin (topical) for the relief of redness, swelling, heat, pain (inflammation) and itching, caused by certain skin problems in people 12 years of age and older. • It is not known if mometasone furoate lotion is safe and effective for use in children under 12 years of age. • Mometasone furoate lotion should not be used in children under 12 years of age. Do not use mometasone furoate lotion if you are allergic to mometasone furoate or any of the ingredients in mometasone furoate lotion. See the end of this leaflet for a complete list of ingredients in mometasone furoate lotion. Before using mometasone furoate lotion, tell your healthcare provider about all your medical conditions, including if you: • have a skin infection at the site to be treated. You may also need medicine to treat the skin infection. • are pregnant or plan to become pregnant. It is not known if mometasone furoate lotion will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if mometasone furoate lotion passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin or scalp that contain corticosteroids. How should I use mometasone furoate lotion? • Use mometasone furoate lotion exactly as your healthcare provider tells you to use it. • Apply a few drops of mometasone furoate lotion to the affected skin area 1 time each day and rub it in lightly until it disappears. • Use mometasone furoate lotion until the affected skin area is improved. Tell your healthcare provider if the treated skin area does not get better after 2 weeks of treatment. • Do not bandage, cover, or wrap the treated skin area unless your health care provider tells you to. • Mometasone furoate lotion should not be used to treat diaper rash or redness. Avoid using mometasone furoate lotion in the diaper area if wearing diapers or plastic pants. • Avoid using mometasone furoate lotion the face, groin, or underarms (armpits). • Wash your hands after applying mometasone furoate lotion. What are the possible side effects of mometasone furoate lotion? Mometasone furoate lotion may cause serious side effects, including: • Mometasone furoate lotion can pass through your skin. Too much mometasone furoate lotion passing through your skin can cause your adrenal glands to stop working properly. Your healthcare provider may do blood tests to check for adrenal gland problems. • Vision problems. Topical corticosteroids may increase your chance of developing vision problems such as cataract and glaucoma. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with mometasone furoate lotion. • Skin problems. Skin problems may happen during treatment with mometasone furoate lotion, including allergic reactions (contact dermatitis) and skin infections at the treatment site.

a. Tell your healthcare provider if you develop blurred vision or other vision problems during treatment with mometasone furoate lotion. • Skin problems. Skin problems may happen during treatment with mometasone furoate lotion, including allergic reactions (contact dermatitis) and skin infections at the treatment site. Stop using mometasone furoate lotion and tell your healthcare provider if you develop any skin reactions such as pain, tenderness, swelling, or problems healing during treatment with mometasone furoate lotion. The most common side effects of mometasone furoate lotion include buring, itching, and inflammation of the hair follicle (folliculitis). These are not all the possible side effects of mometasone furoate lotion. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store mometasone furoate lotion? • Store mometasone furoate lotion at room temperature between 68°F to 77°F (20°C to 25°C). • Keep mometasone furoate lotion and all medicines out of the reach of children. General information about the safe and effective use of mometasone furoate lotion. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use mometasone furoate lotion for a condition for which it was not prescribed. Do not give mometasone furoate lotion to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about mometasone furoate lotion that is written for health professionals. What are the ingredients in mometasone furoate lotion? Active ingredient: mometasone furoate Inactive ingredients: hydroxypropyl cellulose, isopropyl alcohol (40%), propylene glycol, purified water and sodium phosphate monobasic monohydrate. May also contain phosphoric acid used to adjust the pH to approximately 4.5. Manufactured by: Encube Ethicals Pvt. Ltd. Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post: Mardol, Ponda, Goa - 403 404, India. Distributed by: Encube Ethicals, Inc. 200 Meredith Drive, Suite 202 Durham, NC 27713 USA Revised:12/2024

1 INDICATIONS AND USAGE ASMANEX HFA is a corticosteroid indicated for: Maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. ( 1.1 ) Important limitations: Not indicated for the relief of acute bronchospasm. ( 1.1 ) 1.1 Treatment of Asthma ASMANEX ® HFA is indicated for the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. Important Limitations of Use ASMANEX HFA is NOT indicated for the relief of acute bronchospasm.

2 DOSAGE AND ADMINISTRATION For oral inhalation only. ( 2.1 ) Treatment of asthma in patients 12 years of age and older: 2 inhalations twice daily of ASMANEX HFA 100 mcg or 200 mcg. Starting dosage is based on prior asthma therapy. ( 2.2 ) Treatment of asthma in patients aged 5 to less than 12 years: 2 inhalations twice daily of ASMANEX HFA 50 mcg. ( 2.2 ) 2.1 Administration Information Administer ASMANEX HFA only by the orally inhaled route [see Instructions for Use in the Patient Information leaflet ] . After each dose, advise patients to rinse their mouth with water and, without swallowing, spit out the contents to help reduce the risk of oropharyngeal candidiasis. Remove the cap from the mouthpiece of the actuator before using ASMANEX HFA. Prime ASMANEX HFA before using for the first time by releasing 4 test sprays into the air, away from the face, shaking well before each spray. In cases where the inhaler has not been used for more than 5 days, prime the inhaler again by releasing 4 test sprays into the air, away from the face, shaking well before each spray. Only use the ASMANEX HFA canister with the ASMANEX HFA actuator. Do not use the ASMANEX HFA actuator with any other inhalation drug product. Do not use actuators from other products with the ASMANEX HFA canister. 2.2 Recommended Dosage Administer ASMANEX HFA as two inhalations twice daily every day (morning and evening) by the orally inhaled route. Shake well prior to each inhalation. If symptoms arise between doses, use an inhaled short-acting beta 2 -agonist for immediate relief. The maximum benefit may not be achieved for 1 week or longer after beginning treatment. Individual patients may experience a variable time to onset and degree of symptom relief. Adult and Adolescent Patients Aged 12 Years and Older For patients 12 years of age and older, the dosage is either 2 inhalations twice daily of ASMANEX HFA 100 mcg or 200 mcg. The starting dosage is based on previous asthma therapy and disease severity, including considerations of the patients' current control of asthma symptoms and risk of future exacerbations. The recommended starting dosage for patients 12 years of age and older who are not on an inhaled corticosteroid is ASMANEX HFA 100 mcg, 2 inhalations twice daily. It is recommended that patients currently receiving chronic oral corticosteroid therapy (e.g., prednisone) begin with ASMANEX HFA 200 mcg (2 inhalations twice daily). For patients who do not respond adequately to the initial dosage after 2 weeks of therapy, increasing the dosage may provide additional asthma control. The maximum daily recommended dose is two inhalations of ASMANEX HFA 200 mcg twice daily (maximum of 800 mcg a day). After asthma stability has been achieved, it may be desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. If a dosage regimen of ASMANEX HFA fails to provide adequate control of asthma, re-evaluate the therapeutic regimen and consider additional therapeutic options, e.g., replacing the current strength of ASMANEX HFA with a higher strength, initiating an inhaled corticosteroid and long-acting beta 2 -agonist combination product, or initiating oral corticosteroids. Pediatric Patients Aged 5 to Less Than 12 Years For patients aged 5 to less than 12 years, the dosage is 2 inhalations of ASMANEX HFA 50 mcg twice daily. The maximum daily dosage is 200 mcg.

3 DOSAGE FORMS AND STRENGTHS ASMANEX HFA is a pressurized metered dose inhaler (MDI) that is available in 2 strengths (100 mcg and 200 mcg) for adult and adolescent patients aged 12 years and older; and 1 strength (50 mcg) for pediatric patients aged 5 to less than 12 years. ASMANEX HFA 50 mcg delivers 50 mcg of mometasone furoate per actuation. ASMANEX HFA 100 mcg delivers 100 mcg of mometasone furoate per actuation. ASMANEX HFA 200 mcg delivers 200 mcg of mometasone furoate per actuation. Each strength of ASMANEX HFA is supplied with a blue colored actuator and pink dust cap [see How Supplied/Storage and Handling (16.1) ] . Inhalation aerosol containing 50 mcg, 100 mcg, or 200 mcg of mometasone furoate per actuation. ( 3 )

4 CONTRAINDICATIONS Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. ( 4.1 ) Hypersensitivity to any of the ingredients of ASMANEX HFA. ( 4.2 ) 4.1 Status Asthmaticus ASMANEX HFA is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. 4.2 Hypersensitivity ASMANEX HFA is contraindicated in patients with known hypersensitivity to mometasone furoate or any of the ingredients in ASMANEX HFA [see Warnings and Precautions (5.8) ] .

5 WARNINGS AND PRECAUTIONS Deterioration of asthma and acute episodes: ASMANEX HFA should not be used for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. ( 5.1 ) Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. After dosing, advise patients to rinse their mouth with water and spit out contents without swallowing. ( 5.2 ) Immunosuppression: Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Use with caution in patients with these infections because of the potential for worsening of these infections. ( 5.3 ) Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Wean patients slowly from systemic corticosteroids if transferring to ASMANEX HFA. ( 5.4 ) Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ASMANEX HFA slowly. ( 5.5 ) Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with ASMANEX HFA. ( 5.6 ) Paradoxical bronchospasm: Discontinue ASMANEX HFA and institute alternative therapy if paradoxical bronchospasm occurs. ( 5.7 ) Hypersensitivity reactions including anaphylaxis: Hypersensitivity reactions, such as urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reaction may occur. Discontinue ASMANEX HFA if such reactions occur. ( 5.8 ) Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. ( 5.9 ) Effects on growth: Monitor growth of pediatric patients. ( 5.10 ) Glaucoma and cataracts: Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX HFA long term. ( 5.11 ) 5.1 Deterioration of Asthma and Acute Episodes ASMANEX HFA is not indicated for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta 2 -agonist, not ASMANEX HFA, should be used to relieve acute symptoms such as shortness of breath. When prescribing ASMANEX HFA, the physician must also provide the patient with an inhaled, short-acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning and evening) use of ASMANEX HFA. Instruct patients to contact their physician immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with ASMANEX HFA. During such episodes, patients may require therapy with oral corticosteroids. 5.2 Local Effects In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans have occurred in patients treated with ASMANEX HFA. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment with ASMANEX HFA therapy, but at times therapy with ASMANEX HFA may need to be interrupted.

h and pharynx with Candida albicans have occurred in patients treated with ASMANEX HFA. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment with ASMANEX HFA therapy, but at times therapy with ASMANEX HFA may need to be interrupted. To reduce the risk of oropharyngeal candidiasis, after dosing with ASMANEX HFA, advise patients to rinse their mouth with water and spit out the contents without swallowing. 5.3 Immunosuppression Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or who are not properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. 5.4 Transferring Patients from Systemic Corticosteroid Therapy Particular care is needed for patients who are transferred from systemically active corticosteroids to ASMANEX HFA because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although ASMANEX HFA may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity necessary for coping with these emergencies. During periods of stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack. Patients requiring oral or other systemic corticosteroids should be weaned slowly from oral or other systemic corticosteroid use after transferring to ASMANEX HFA.

o carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack. Patients requiring oral or other systemic corticosteroids should be weaned slowly from oral or other systemic corticosteroid use after transferring to ASMANEX HFA. Lung function (FEV 1 or PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral or other systemic corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to ASMANEX HFA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function. 5.5 Hypercorticism and Adrenal Suppression ASMANEX HFA will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since mometasone furoate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of ASMANEX HFA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with ASMANEX HFA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when mometasone furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of ASMANEX HFA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms. 5.6 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of ASMANEX HFA with ketoconazole, and other known strong cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to mometasone furoate may occur [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. 5.7 Paradoxical Bronchospasm and Upper Airway Symptoms ASMANEX HFA may produce inhalation induced bronchospasm with an immediate increase in wheezing after dosing that may be life-threatening. If inhalation induced bronchospasm occurs, it should be treated immediately with an inhaled, short-acting bronchodilator. ASMANEX HFA should be discontinued immediately and alternative therapy instituted. 5.8 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions such as urticaria, flushing, allergic dermatitis, and bronchospasm, may occur after administration of ASMANEX HFA. Discontinue ASMANEX HFA if such reactions occur [see Contraindications (4.2) ].

mediately and alternative therapy instituted. 5.8 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions such as urticaria, flushing, allergic dermatitis, and bronchospasm, may occur after administration of ASMANEX HFA. Discontinue ASMANEX HFA if such reactions occur [see Contraindications (4.2) ]. The following additional hypersensitivity reactions, such as rash, pruritus, angioedema, and anaphylactic reaction, have been reported after administration of mometasone furoate dry powder inhaler (DPI) [see Adverse Reactions (6.2) ]. 5.9 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. In a 2-year double-blind study in 103 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV 1 85%-88% predicted), treatment with mometasone furoate dry powder inhaler 200 mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.015 (-1.43%) for the mometasone furoate dry powder inhaler group compared to 0.002 (0.25%) for the placebo group. In another 2-year double-blind study in 87 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV 1 82%-83% predicted), treatment with mometasone furoate dry powder inhaler 400 mcg twice daily demonstrated no statistically significant changes in lumbar spine BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.018 (-1.57%) for the mometasone furoate group compared to -0.006 (-0.43%) for the placebo group. 5.10 Effect on Growth Orally inhaled corticosteroids, including ASMANEX HFA, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving ASMANEX HFA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX HFA, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4) ] . 5.11 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of long-term administration of inhaled corticosteroids, including mometasone furoate. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX HFA long term [see Adverse Reactions (6) ] .

6 ADVERSE REACTIONS Systemic and local corticosteroid use may result in the following: Candida albicans infection [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.3) ] Hypercorticism and adrenal suppression [see Warnings and Precautions (5.5) ] Growth effects in pediatrics [see Warnings and Precautions (5.10) ] Glaucoma and cataracts [see Warnings and Precautions (5.11) ] 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 practice. Most common adverse reactions (reported in greater than or equal to 3% of patients) included: nasopharyngitis, headache, sinusitis, bronchitis, and influenza. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Adult and Adolescent Patients Aged 12 Years and Older The safety of ASMANEX HFA was evaluated in 2 randomized placebo and active-controlled trials of 12 and 26 weeks' duration, conducted as part of a mometasone furoate/formoterol fumarate combination product asthma program, which enrolled 1509 patients with persistent asthma. Patient ages ranged from 12 to 84 years of age, 41% were male and 59% female, 73% were Caucasian and 27% non-Caucasian. Of the total population enrolled in the 2 trials, 432 patients received two inhalations twice daily of either ASMANEX HFA, 100 mcg or 200 mcg/actuation. In the 26-week trial (Trial 1) 192 patients received two inhalations twice daily of ASMANEX HFA 100 mcg/actuation and 196 patients received placebo. In the 12 week trial (Trial 2) 240 patients received two inhalations twice daily of ASMANEX HFA 200 mcg/actuation and 233 and 255 patients received mometasone furoate and formoterol fumarate 100 mcg/5 mcg and 200 mcg/5 mcg/actuation combination products, respectively, as comparators. In these trials, the proportion of patients who discontinued study treatment early due to adverse reactions was 3% and 2% for ASMANEX HFA 100 and 200 mcg treated patients, respectively, and 4% for placebo-treated patients. Serious adverse reactions, whether considered drug-related or not by the investigators, which occurred more frequently in ASMANEX HFA-treated patients included colitis ulcerative, colonic polyp, chest pain, gastroenteritis, endometriosis, asthma, and hemoptysis; all events occurred at rates less than 1%. The incidence of treatment emergent adverse events associated with ASMANEX HFA are shown in Tables 1 and 2. These are based upon data from each of the 2 clinical trials of 12 or 26 weeks in duration in patients 12 years and older treated with two inhalations twice daily of ASMANEX HFA (100 mcg or 200 mcg), mometasone furoate/formoterol fumarate (100 mcg/5 mcg or 200 mcg/5 mcg), or placebo. TABLE 1: Trial 1: Treatment-Emergent Adverse Events Occurring at an Incidence of ≥3% and More Commonly than Placebo Over 26 Weeks ASMANEX HFA 100 mcg N=192 n (%) Placebo N=196 n (%) Nasopharyngitis 15 (8) 7 (4) Headache 10 (5) 7 (4) Influenza 7 (4) 5 (3) Sinusitis 6 (3) 2 (1) TABLE 2: Trial 2: Treatment-Emergent Adverse Events Occurring at an Incidence of ≥3% Over 12 Weeks ASMANEX HFA 200 mcg N=240 n (%) MF/F MF/F = mometasone furoate/formoterol fumarate.

FA 100 mcg N=192 n (%) Placebo N=196 n (%) Nasopharyngitis 15 (8) 7 (4) Headache 10 (5) 7 (4) Influenza 7 (4) 5 (3) Sinusitis 6 (3) 2 (1) TABLE 2: Trial 2: Treatment-Emergent Adverse Events Occurring at an Incidence of ≥3% Over 12 Weeks ASMANEX HFA 200 mcg N=240 n (%) MF/F MF/F = mometasone furoate/formoterol fumarate. 100/5 mcg N=233 n (%) MF/F 200/5 mcg N=255 n (%) Nasopharyngitis 13 (5) 8 (3) 12 (5) Headache 8 (3) 10 (4) 5 (2) Bronchitis 6 (3) 2 (1) 7 (3) Oral candidiasis has been reported in clinical trials at an incidence of 0.5% in patients using ASMANEX HFA 100 mcg, 0.8% in patients using ASMANEX HFA 200 mcg and 0.5% in the placebo group. Pediatric Patients Aged 5 to Less Than 12 Years The safety profile for ASMANEX HFA 50 mcg, 2 inhalations twice daily, is based on two clinical trials consisting of a total of 759 patients aged 5 to less than 12 years with persistent asthma. The first trial was a placebo-controlled trial comparing ASMANEX HFA 50 mcg (administered as 2 inhalations, twice daily) to 2 other dosage strengths of mometasone furoate MDI (25 mcg or 100 mcg, each administered as two inhalations, twice daily) as well as mometasone furoate DPI 100 mcg, administered as one evening inhalation. The second trial compared ASMANEX HFA 50 mcg to the combination of mometasone furoate and formoterol fumarate 50 mcg/5 mcg, each administered by MDI as two inhalations, twice daily. Overall, the safety profile for pediatric patients is similar to that observed in patients aged 12 years and older. 6.2 Postmarketing Experience There are no postmarketing adverse experiences reported to date with ASMANEX HFA. However, the postmarketing safety experience with mometasone furoate dry powder inhaler is relevant to ASMANEX HFA since they contain the same active ingredient. The following adverse reactions have been reported during post-approval use of mometasone furoate dry powder inhaler. Because these 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. Eye Disorders: Vision blurred [see Warnings and Precautions (5.11) ] . Immune System Disorders: Immediate and delayed hypersensitivity reactions including rash, pruritus, angioedema and anaphylactic reaction [see Contraindications (4.2) and Warnings and Precautions (5.8) ] . Respiratory, Thoracic and Mediastinal Disorders: Asthma aggravation, which may include cough, dyspnea, wheezing and bronchospasm.

<table width="75%" ID="table2"><caption>TABLE 1: Trial 1: Treatment-Emergent Adverse Events Occurring at an Incidence of &#x2265;3% and More Commonly than Placebo Over 26 Weeks</caption><col width="33%" valign="top" align="left"/><col width="35%" valign="top" align="center"/><col width="32%" valign="top" align="center"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">ASMANEX HFA 100 mcg N=192 n (%)</th><th styleCode="Rrule">Placebo N=196 n (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">15 (8)</td><td styleCode="Rrule">7 (4)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">10 (5)</td><td styleCode="Rrule">7 (4)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Influenza</td><td styleCode="Rrule">7 (4)</td><td styleCode="Rrule">5 (3)</td></tr><tr><td styleCode="Lrule Rrule">Sinusitis</td><td styleCode="Rrule">6 (3)</td><td styleCode="Rrule">2 (1)</td></tr></tbody></table> <table width="75%" ID="table3"><caption>TABLE 2: Trial 2: Treatment-Emergent Adverse Events Occurring at an Incidence of &#x2265;3% Over 12 Weeks</caption><col width="25%" valign="top" align="left"/><col width="25%" valign="top" align="center"/><col width="25%" valign="top" align="center"/><col width="25%" valign="top" align="center"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">ASMANEX HFA 200 mcg N=240 n (%)</th><th styleCode="Rrule">MF/F<footnote ID="tb3ft">MF/F = mometasone furoate/formoterol fumarate.</footnote> 100/5 mcg N=233 n (%)</th><th styleCode="Rrule">MF/F<footnoteRef IDREF="tb3ft"/> 200/5 mcg N=255 n (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nasopharyngitis</td><td styleCode="Rrule">13 (5)</td><td styleCode="Rrule">8 (3)</td><td styleCode="Rrule">12 (5)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">8 (3)</td><td styleCode="Rrule">10 (4)</td><td styleCode="Rrule">5 (2)</td></tr><tr><td styleCode="Lrule Rrule">Bronchitis</td><td styleCode="Rrule">6 (3)</td><td styleCode="Rrule">2 (1)</td><td styleCode="Rrule">7 (3)</td></tr></tbody></table>

7 DRUG INTERACTIONS In clinical trials, concurrent administration of ASMANEX HFA and other drugs, such as short-acting beta 2 -agonist and intranasal corticosteroids have not resulted in an increased frequency of adverse drug reactions. No formal drug interaction studies have been performed with ASMANEX HFA. Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. ( 7.1 ) 7.1 Inhibitors of Cytochrome P450 3A4 The main route of metabolism of corticosteroids, including mometasone furoate, is via CYP3A4. After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally inhaled mometasone furoate increased. Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, mometasone furoate and potentially increase the risk for systemic corticosteroid side effects. Caution should be exercised when considering the coadministration of ASMANEX HFA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) ] . Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side effects.

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Monitor patients for signs of increased drug exposure. ( 8.6 ) 8.1 Pregnancy Risk Summary There are no randomized clinical studies of ASMANEX HFA in pregnant women. There are clinical considerations with the use of ASMANEX HFA in pregnant women [see Clinical Considerations ] . In animal reproduction studies with pregnant mice, rats, or rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data ] . However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at an exposure approximately one-third of the MRHD (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately one-tenth of the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure that was approximately 8 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 4 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis.

were no findings with an exposure approximately 4 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at an exposure approximately 1/2 of the MRHD (on AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg). 8.2 Lactation Risk Summary There are no available data on the presence of ASMANEX HFA in human milk, the effects on the breastfed child, or the effects on milk production. Other inhaled corticosteroids, similar to mometasone furoate, are present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ASMANEX HFA and any potential adverse effects on the breastfed infant from ASMANEX HFA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ASMANEX HFA have been established in patients 12 years of age and older in 2 clinical trials of 12 and 26 weeks in duration. In the 2 clinical trials, 32 patients 12 to 17 years of age were treated with ASMANEX HFA. No overall differences in effectiveness were observed between patients in this age group compared to those observed in patients 18 years of age and older. There were no obvious differences in the type or frequency of adverse reactions reported in this age group compared to patients 18 years of age and older. The safety and effectiveness of ASMANEX HFA 50 mcg, two inhalations twice daily, have been established in patients with asthma aged 5 to less than 12 years in clinical trials up to 24 weeks of treatment duration. The safety profile and overall effectiveness in this age group were consistent with that observed in patients aged 12 years and older who also received ASMANEX HFA [see Adverse Reactions (6.1) and Clinical Studies (14.1) ]. The safety and effectiveness of ASMANEX HFA have not been established in children younger than 5 years of age. Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 cm per year (range 0.3 to 1.8 per year) and appears to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied.

is function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The growth of children and adolescents receiving orally inhaled corticosteroids, including ASMANEX HFA, should be monitored routinely (e.g., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX HFA, each patient should be titrated to his/her lowest effective dose [see Dosage and Administration (2.2) ] . 8.5 Geriatric Use A total of 38 patients 65 years of age and older (3 of whom were 75 years and older) have been treated with ASMANEX HFA in 2 clinical trials of 12 and 26 weeks in duration. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on available data for ASMANEX HFA, no adjustment of dosage in geriatric patients is warranted. 8.6 Hepatic Impairment Concentrations of mometasone furoate appear to increase with severity of hepatic impairment [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Risk Summary There are no randomized clinical studies of ASMANEX HFA in pregnant women. There are clinical considerations with the use of ASMANEX HFA in pregnant women [see Clinical Considerations ] . In animal reproduction studies with pregnant mice, rats, or rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data ] . However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at an exposure approximately one-third of the MRHD (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately one-tenth of the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure that was approximately 8 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 4 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above).

genesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at an exposure approximately 1/2 of the MRHD (on AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg).

8.4 Pediatric Use The safety and effectiveness of ASMANEX HFA have been established in patients 12 years of age and older in 2 clinical trials of 12 and 26 weeks in duration. In the 2 clinical trials, 32 patients 12 to 17 years of age were treated with ASMANEX HFA. No overall differences in effectiveness were observed between patients in this age group compared to those observed in patients 18 years of age and older. There were no obvious differences in the type or frequency of adverse reactions reported in this age group compared to patients 18 years of age and older. The safety and effectiveness of ASMANEX HFA 50 mcg, two inhalations twice daily, have been established in patients with asthma aged 5 to less than 12 years in clinical trials up to 24 weeks of treatment duration. The safety profile and overall effectiveness in this age group were consistent with that observed in patients aged 12 years and older who also received ASMANEX HFA [see Adverse Reactions (6.1) and Clinical Studies (14.1) ]. The safety and effectiveness of ASMANEX HFA have not been established in children younger than 5 years of age. Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 cm per year (range 0.3 to 1.8 per year) and appears to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The growth of children and adolescents receiving orally inhaled corticosteroids, including ASMANEX HFA, should be monitored routinely (e.g., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX HFA, each patient should be titrated to his/her lowest effective dose [see Dosage and Administration (2.2) ] .

8.5 Geriatric Use A total of 38 patients 65 years of age and older (3 of whom were 75 years and older) have been treated with ASMANEX HFA in 2 clinical trials of 12 and 26 weeks in duration. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on available data for ASMANEX HFA, no adjustment of dosage in geriatric patients is warranted.

10 OVERDOSAGE Chronic overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.5) ] . Single oral doses up to 8000 mcg of mometasone furoate have been studied on adult subjects with no adverse reactions reported.

11 DESCRIPTION ASMANEX HFA is a metered dose inhaler for oral inhalation only, consisting of 50 mcg, 100 mcg, or 200 mcg of mometasone furoate per actuation. Mometasone furoate, the active component of ASMANEX HFA, is a corticosteroid having the chemical name 9,21-dichloro-11(Beta),17-dihydroxy-16 (alpha)-methylpregna-1,4-diene-3,20-dione 17-(2-furoate) with the following chemical structure: Mometasone furoate is a white powder with an empirical formula of C 27 H 30 Cl 2 O 6 , and molecular weight 521.44. It is practically insoluble in water; slightly soluble in methanol, ethanol, and isopropanol; soluble in acetone. ASMANEX HFA 50 mcg, 100 mcg, and 200 mcg are each formulated as a hydrofluoroalkane (HFA-227: 1,1,1,2,3,3,3-heptafluoropropane) propelled pressurized metered dose inhaler containing sufficient amount of drug for 120 actuations [see How Supplied/Storage and Handling (16) ] . After priming, each actuation of the inhaler delivers 60, 115, or 225 mcg of mometasone furoate in 69.6 mg of suspension from the valve and delivers 50, 100, or 200 mcg of mometasone furoate from the actuator. The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between actuation of the device and inspiration through the delivery system. ASMANEX HFA also contains ethanol as a cosolvent and oleic acid as a surfactant. ASMANEX HFA should be primed before using for the first time by releasing 4 test sprays into the air, away from the face, shaking well before each spray. In cases where the inhaler has not been used for more than 5 days, prime the inhaler again by releasing 4 test sprays into the air, away from the face, shaking well before each spray. Chemical Structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mometasone furoate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation and in the asthmatic response. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown. 12.2 Pharmacodynamics Systemic effects of inhaled corticosteroids are related to systemic exposure. Pharmacokinetic data have demonstrated that, in adults, systemic exposure to mometasone furoate administered by MDI is the same or lower than that of equivalent doses of inhaled mometasone furoate administered via DPI [see Clinical Pharmacology (12.3) ] . Based upon the pharmacokinetic data, the systemic effects (e.g., HPA-axis suppression and growth retardation) of mometasone furoate delivered by MDI in adult and pediatric patients would be expected to be no greater than what is reported for inhaled mometasone furoate when administered at comparable doses via DPI [see Use in Specific Populations (8.4) ] . HPA Axis Effects (Adults) The effects of inhaled mometasone furoate administered via ASMANEX HFA on adrenal function have not been directly evaluated. However, the effects of inhaled mometasone furoate, administered as part of a mometasone furoate/formoterol fumarate inhalation aerosol combination product, on adrenal function were evaluated in two clinical trials in patients with asthma. As no evidence of a pharmacokinetic drug interaction between mometasone furoate and formoterol was observed when the two drugs were administered in combination, the HPA axis effects from the combination product are applicable to ASMANEX HFA. For the mometasone furoate/formoterol fumarate combination product clinical program, HPA-axis function was assessed by 24-hour plasma cortisol AUC. Although both these trials have open-label design and contain a small number of subjects per treatment arm, results from these trials taken together demonstrated suppression of 24-hour plasma cortisol AUC for the combination mometasone furoate/formoterol fumarate 200 mcg/5 mcg compared to placebo consistent with the known systemic effects of inhaled corticosteroid. In a 42-day, open-label, placebo- and active-controlled study, the mean change from baseline plasma cortisol AUC (0-24 hr) was 8%, 22% and 34% lower compared to placebo for the mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=13), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=15) and fluticasone propionate/salmeterol xinafoate 230 mcg/21 mcg (n=16) treatment groups, respectively.

from baseline plasma cortisol AUC (0-24 hr) was 8%, 22% and 34% lower compared to placebo for the mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=13), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=15) and fluticasone propionate/salmeterol xinafoate 230 mcg/21 mcg (n=16) treatment groups, respectively. In a 52-week, open-label safety study, the mean plasma cortisol AUC (0-24 hr) was 2.2%, 29.6%, 16.7%, and 32.2% lower from baseline for the mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=18), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=20), fluticasone propionate/salmeterol xinafoate 125/25 mcg (n=8), and fluticasone propionate/salmeterol xinafoate 250/25 mcg (n=11) treatment groups, respectively. The potential effect of mometasone furoate via a dry powder inhaler (DPI) on the HPA axis was also assessed in a 29-day study. A total of 64 adult patients with mild to moderate asthma were randomized to one of 4 treatment groups: mometasone furoate DPI 440 mcg twice daily, mometasone furoate DPI 880 mcg twice daily, oral prednisone 10 mg once daily, or placebo. The 30-minute post-Cosyntropin stimulation serum cortisol concentration on Day 29 was 23.2 mcg/dL for the mometasone furoate DPI 440 mcg twice daily group and 20.8 mcg/dL for the mometasone furoate DPI 880 mcg twice daily group, compared to 14.5 mcg/dL for the oral prednisone 10 mg group and 25 mcg/dL for the placebo group. The difference between mometasone furoate DPI 880 mcg twice daily (twice the maximum recommended dose) and placebo was statistically significant. HPA Axis Effects (Pediatrics) The potential effect of mometasone furoate via a DPI on the HPA axis was assessed in 50 children aged 6 to 11 years in a 29-day, randomized, double-blind, placebo-controlled, parallel-group clinical trial. In this study, the mean difference from placebo in plasma cortisol AUC (0-12hr) for DPI 110 mcg twice daily was 3.4 mcg∙hr/dL (95% CI: -14.0, 20.7) and for 220 mcg twice daily was -16.0 mcg∙hr/dL (95% CI: -33.9, 1.9). The mean difference from placebo in plasma cortisol AUC (0-12hr) for the 440 mcg twice daily group (eight times the currently recommended mometasone furoate dose via a DPI in children ages 4-11) was -17.9 mcg∙hr/dL (95% CI: -35.8, 0.0). The mean differences in urinary-free cortisol changes from baseline compared to placebo were 3.1 mcg/day (95% CI: -3.3, 9.6), 3.3 mcg/day (95% CI: -3.0, 9.7), and -2.0 mcg/day (95% CI: -8.6, 4.6) for the groups treated with 110 mcg twice daily, 220 mcg twice daily, and 440 mcg twice daily, respectively. 12.3 Pharmacokinetics As no evidence of a pharmacokinetic drug interaction between mometasone furoate and formoterol was observed when the two drugs were administered from a mometasone furoate/formoterol fumarate combination product, the pharmacokinetics information from the combination product is applicable to ASMANEX HFA. Absorption Adult Healthy Subjects: Following oral inhalation of single doses of ASMANEX HFA, mometasone furoate was absorbed in healthy subjects with median T max values ranging from 0.50 to 2 hours. Following single-dose administration of higher than recommended dose of ASMANEX HFA (4 inhalations of ASMANEX HFA 200 mcg) in healthy subjects, the arithmetic mean (CV%) C max and AUC (0-tf) values for mometasone furoate were 53 (102) pg/mL and 992 (80) pg∙hr/mL, respectively. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of mometasone furoate is negligible (<1%).

200 mcg) in healthy subjects, the arithmetic mean (CV%) C max and AUC (0-tf) values for mometasone furoate were 53 (102) pg/mL and 992 (80) pg∙hr/mL, respectively. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of mometasone furoate is negligible (<1%). Following single-dose administration of a higher than recommended dose of mometasone furoate (4 inhalations of mometasone furoate/formoterol fumarate 200 mcg/5 mcg) in healthy subjects, the arithmetic mean (CV%) C max and AUC (0-12 hr) values for mometasone furoate were 67.8 (49) pg/mL and 650 (51) pg∙hr/mL, respectively, while the corresponding estimates following 5 days of BID dosing with mometasone furoate 800 mcg/20 mcg were 241 (36) pg/mL and 2200 (35) pg∙hr/mL. The systemic exposure to mometasone furoate (based on AUC) was approximately 52% and 25% lower on Day 1 and Day 5, respectively, following mometasone furoate administration compared to mometasone furoate via a DPI. Adult Asthma Patients: Following oral inhalation of single and multiple doses of the mometasone furoate/formoterol fumarate combination product, mometasone furoate was absorbed in asthma patients with median T max values ranging from 1 to 2 hours. Following single-dose administration of mometasone furoate/formoterol fumarate 400 mcg/10 mcg, the arithmetic mean (CV%) C max and AUC (0-12 hr) values for mometasone furoate were 20 (88) pg/mL and 170 (94) pg∙hr/mL, respectively, while the corresponding estimates following twice daily dosing of mometasone furoate/formoterol fumarate 400 mcg/10 mcg at steady-state were 60 (36) pg/mL and 577 (40) pg∙hr/mL. Distribution Based on the study employing a 1000 mcg inhaled dose of tritiated mometasone furoate inhalation powder in humans, no appreciable accumulation of mometasone furoate in the red blood cells was found. Following an intravenous 400 mcg dose of mometasone furoate, the plasma concentrations showed a biphasic decline, with a mean steady-state volume of distribution of 152 liters. The in vitro protein binding for mometasone furoate was reported to be 98% to 99% (in a concentration range of 5 to 500 ng/mL). Metabolism Studies have shown that mometasone furoate is primarily and extensively metabolized in the liver of all species investigated and undergoes extensive metabolism to multiple metabolites. In vitro studies have confirmed the primary role of human liver CYP3A4 in the metabolism of this compound; however, no major metabolites were identified. Human liver CYP3A4 metabolizes mometasone furoate to 6-beta hydroxy mometasone furoate. Excretion Following an intravenous dosing, the terminal half-life was reported to be about 5 hours. Following the inhaled dose of tritiated 1000 mcg mometasone furoate, the radioactivity is excreted mainly in the feces (a mean of 74%), and to a small extent in the urine (a mean of 8%) up to 7 days. No radioactivity was associated with unchanged mometasone furoate in the urine. Absorbed mometasone furoate is cleared from plasma at a rate of approximately 12.5 mL/min/kg, independent of dose. The effective t ½ for mometasone furoate following inhalation was 25 hours in adult healthy subjects and in adult patients with asthma. Special Populations Hepatic/Renal Impairment: There are no data regarding the specific use of ASMANEX HFA in patients with hepatic or renal impairment. A study evaluating the administration of a single inhaled dose of 400 mcg mometasone furoate by a dry powder inhaler to adult subjects with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable peak plasma concentrations of mometasone furoate (ranging from 50-105 pg/mL).

inistration of a single inhaled dose of 400 mcg mometasone furoate by a dry powder inhaler to adult subjects with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable peak plasma concentrations of mometasone furoate (ranging from 50-105 pg/mL). The observed peak plasma concentrations appear to increase with severity of hepatic impairment; however, the numbers of detectable levels were few. Gender and Race: Specific studies to examine the effects of gender and race on the pharmacokinetics of ASMANEX HFA have not been specifically studied. Geriatrics: The pharmacokinetics of ASMANEX HFA have not been specifically studied in the elderly population. Drug-Drug Interactions A single-dose crossover study was conducted to compare the pharmacokinetics of 4 inhalations of the following: mometasone furoate MDI, formoterol MDI, mometasone furoate/formoterol fumarate MDI combination product, and mometasone furoate MDI plus formoterol fumarate MDI administered concurrently. The results of the study indicated that there was no evidence of a pharmacokinetic interaction between mometasone furoate and formoterol. Inhibitors of Cytochrome P450 Enzymes: Ketoconazole: In a drug interaction study, an inhaled dose of mometasone furoate 400 mcg delivered by a dry powder inhaler was given to 24 adult healthy subjects twice daily for 9 days and ketoconazole 200 mg (as well as placebo) were given twice daily concomitantly on Days 4 to 9. Mometasone furoate plasma concentrations were <150 pg/mL on Day 3 prior to coadministration of ketoconazole or placebo. Following concomitant administration of ketoconazole, 4 out of 12 subjects in the ketoconazole treatment group (n=12) had peak plasma concentrations of mometasone furoate >200 pg/mL on Day 9 (211-324 pg/mL). Mometasone furoate plasma levels appeared to increase and plasma cortisol levels appeared to decrease upon concomitant administration of ketoconazole.

12.1 Mechanism of Action Mometasone furoate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation and in the asthmatic response. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.

12.2 Pharmacodynamics Systemic effects of inhaled corticosteroids are related to systemic exposure. Pharmacokinetic data have demonstrated that, in adults, systemic exposure to mometasone furoate administered by MDI is the same or lower than that of equivalent doses of inhaled mometasone furoate administered via DPI [see Clinical Pharmacology (12.3) ] . Based upon the pharmacokinetic data, the systemic effects (e.g., HPA-axis suppression and growth retardation) of mometasone furoate delivered by MDI in adult and pediatric patients would be expected to be no greater than what is reported for inhaled mometasone furoate when administered at comparable doses via DPI [see Use in Specific Populations (8.4) ] . HPA Axis Effects (Adults) The effects of inhaled mometasone furoate administered via ASMANEX HFA on adrenal function have not been directly evaluated. However, the effects of inhaled mometasone furoate, administered as part of a mometasone furoate/formoterol fumarate inhalation aerosol combination product, on adrenal function were evaluated in two clinical trials in patients with asthma. As no evidence of a pharmacokinetic drug interaction between mometasone furoate and formoterol was observed when the two drugs were administered in combination, the HPA axis effects from the combination product are applicable to ASMANEX HFA. For the mometasone furoate/formoterol fumarate combination product clinical program, HPA-axis function was assessed by 24-hour plasma cortisol AUC. Although both these trials have open-label design and contain a small number of subjects per treatment arm, results from these trials taken together demonstrated suppression of 24-hour plasma cortisol AUC for the combination mometasone furoate/formoterol fumarate 200 mcg/5 mcg compared to placebo consistent with the known systemic effects of inhaled corticosteroid. In a 42-day, open-label, placebo- and active-controlled study, the mean change from baseline plasma cortisol AUC (0-24 hr) was 8%, 22% and 34% lower compared to placebo for the mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=13), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=15) and fluticasone propionate/salmeterol xinafoate 230 mcg/21 mcg (n=16) treatment groups, respectively. In a 52-week, open-label safety study, the mean plasma cortisol AUC (0-24 hr) was 2.2%, 29.6%, 16.7%, and 32.2% lower from baseline for the mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=18), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=20), fluticasone propionate/salmeterol xinafoate 125/25 mcg (n=8), and fluticasone propionate/salmeterol xinafoate 250/25 mcg (n=11) treatment groups, respectively. The potential effect of mometasone furoate via a dry powder inhaler (DPI) on the HPA axis was also assessed in a 29-day study. A total of 64 adult patients with mild to moderate asthma were randomized to one of 4 treatment groups: mometasone furoate DPI 440 mcg twice daily, mometasone furoate DPI 880 mcg twice daily, oral prednisone 10 mg once daily, or placebo. The 30-minute post-Cosyntropin stimulation serum cortisol concentration on Day 29 was 23.2 mcg/dL for the mometasone furoate DPI 440 mcg twice daily group and 20.8 mcg/dL for the mometasone furoate DPI 880 mcg twice daily group, compared to 14.5 mcg/dL for the oral prednisone 10 mg group and 25 mcg/dL for the placebo group.

0-minute post-Cosyntropin stimulation serum cortisol concentration on Day 29 was 23.2 mcg/dL for the mometasone furoate DPI 440 mcg twice daily group and 20.8 mcg/dL for the mometasone furoate DPI 880 mcg twice daily group, compared to 14.5 mcg/dL for the oral prednisone 10 mg group and 25 mcg/dL for the placebo group. The difference between mometasone furoate DPI 880 mcg twice daily (twice the maximum recommended dose) and placebo was statistically significant. HPA Axis Effects (Pediatrics) The potential effect of mometasone furoate via a DPI on the HPA axis was assessed in 50 children aged 6 to 11 years in a 29-day, randomized, double-blind, placebo-controlled, parallel-group clinical trial. In this study, the mean difference from placebo in plasma cortisol AUC (0-12hr) for DPI 110 mcg twice daily was 3.4 mcg∙hr/dL (95% CI: -14.0, 20.7) and for 220 mcg twice daily was -16.0 mcg∙hr/dL (95% CI: -33.9, 1.9). The mean difference from placebo in plasma cortisol AUC (0-12hr) for the 440 mcg twice daily group (eight times the currently recommended mometasone furoate dose via a DPI in children ages 4-11) was -17.9 mcg∙hr/dL (95% CI: -35.8, 0.0). The mean differences in urinary-free cortisol changes from baseline compared to placebo were 3.1 mcg/day (95% CI: -3.3, 9.6), 3.3 mcg/day (95% CI: -3.0, 9.7), and -2.0 mcg/day (95% CI: -8.6, 4.6) for the groups treated with 110 mcg twice daily, 220 mcg twice daily, and 440 mcg twice daily, respectively.

12.3 Pharmacokinetics As no evidence of a pharmacokinetic drug interaction between mometasone furoate and formoterol was observed when the two drugs were administered from a mometasone furoate/formoterol fumarate combination product, the pharmacokinetics information from the combination product is applicable to ASMANEX HFA. Absorption Adult Healthy Subjects: Following oral inhalation of single doses of ASMANEX HFA, mometasone furoate was absorbed in healthy subjects with median T max values ranging from 0.50 to 2 hours. Following single-dose administration of higher than recommended dose of ASMANEX HFA (4 inhalations of ASMANEX HFA 200 mcg) in healthy subjects, the arithmetic mean (CV%) C max and AUC (0-tf) values for mometasone furoate were 53 (102) pg/mL and 992 (80) pg∙hr/mL, respectively. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of mometasone furoate is negligible (<1%). Following single-dose administration of a higher than recommended dose of mometasone furoate (4 inhalations of mometasone furoate/formoterol fumarate 200 mcg/5 mcg) in healthy subjects, the arithmetic mean (CV%) C max and AUC (0-12 hr) values for mometasone furoate were 67.8 (49) pg/mL and 650 (51) pg∙hr/mL, respectively, while the corresponding estimates following 5 days of BID dosing with mometasone furoate 800 mcg/20 mcg were 241 (36) pg/mL and 2200 (35) pg∙hr/mL. The systemic exposure to mometasone furoate (based on AUC) was approximately 52% and 25% lower on Day 1 and Day 5, respectively, following mometasone furoate administration compared to mometasone furoate via a DPI. Adult Asthma Patients: Following oral inhalation of single and multiple doses of the mometasone furoate/formoterol fumarate combination product, mometasone furoate was absorbed in asthma patients with median T max values ranging from 1 to 2 hours. Following single-dose administration of mometasone furoate/formoterol fumarate 400 mcg/10 mcg, the arithmetic mean (CV%) C max and AUC (0-12 hr) values for mometasone furoate were 20 (88) pg/mL and 170 (94) pg∙hr/mL, respectively, while the corresponding estimates following twice daily dosing of mometasone furoate/formoterol fumarate 400 mcg/10 mcg at steady-state were 60 (36) pg/mL and 577 (40) pg∙hr/mL. Distribution Based on the study employing a 1000 mcg inhaled dose of tritiated mometasone furoate inhalation powder in humans, no appreciable accumulation of mometasone furoate in the red blood cells was found. Following an intravenous 400 mcg dose of mometasone furoate, the plasma concentrations showed a biphasic decline, with a mean steady-state volume of distribution of 152 liters. The in vitro protein binding for mometasone furoate was reported to be 98% to 99% (in a concentration range of 5 to 500 ng/mL). Metabolism Studies have shown that mometasone furoate is primarily and extensively metabolized in the liver of all species investigated and undergoes extensive metabolism to multiple metabolites. In vitro studies have confirmed the primary role of human liver CYP3A4 in the metabolism of this compound; however, no major metabolites were identified. Human liver CYP3A4 metabolizes mometasone furoate to 6-beta hydroxy mometasone furoate. Excretion Following an intravenous dosing, the terminal half-life was reported to be about 5 hours.

confirmed the primary role of human liver CYP3A4 in the metabolism of this compound; however, no major metabolites were identified. Human liver CYP3A4 metabolizes mometasone furoate to 6-beta hydroxy mometasone furoate. Excretion Following an intravenous dosing, the terminal half-life was reported to be about 5 hours. Following the inhaled dose of tritiated 1000 mcg mometasone furoate, the radioactivity is excreted mainly in the feces (a mean of 74%), and to a small extent in the urine (a mean of 8%) up to 7 days. No radioactivity was associated with unchanged mometasone furoate in the urine. Absorbed mometasone furoate is cleared from plasma at a rate of approximately 12.5 mL/min/kg, independent of dose. The effective t ½ for mometasone furoate following inhalation was 25 hours in adult healthy subjects and in adult patients with asthma. Special Populations Hepatic/Renal Impairment: There are no data regarding the specific use of ASMANEX HFA in patients with hepatic or renal impairment. A study evaluating the administration of a single inhaled dose of 400 mcg mometasone furoate by a dry powder inhaler to adult subjects with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable peak plasma concentrations of mometasone furoate (ranging from 50-105 pg/mL). The observed peak plasma concentrations appear to increase with severity of hepatic impairment; however, the numbers of detectable levels were few. Gender and Race: Specific studies to examine the effects of gender and race on the pharmacokinetics of ASMANEX HFA have not been specifically studied. Geriatrics: The pharmacokinetics of ASMANEX HFA have not been specifically studied in the elderly population. Drug-Drug Interactions A single-dose crossover study was conducted to compare the pharmacokinetics of 4 inhalations of the following: mometasone furoate MDI, formoterol MDI, mometasone furoate/formoterol fumarate MDI combination product, and mometasone furoate MDI plus formoterol fumarate MDI administered concurrently. The results of the study indicated that there was no evidence of a pharmacokinetic interaction between mometasone furoate and formoterol. Inhibitors of Cytochrome P450 Enzymes: Ketoconazole: In a drug interaction study, an inhaled dose of mometasone furoate 400 mcg delivered by a dry powder inhaler was given to 24 adult healthy subjects twice daily for 9 days and ketoconazole 200 mg (as well as placebo) were given twice daily concomitantly on Days 4 to 9. Mometasone furoate plasma concentrations were <150 pg/mL on Day 3 prior to coadministration of ketoconazole or placebo. Following concomitant administration of ketoconazole, 4 out of 12 subjects in the ketoconazole treatment group (n=12) had peak plasma concentrations of mometasone furoate >200 pg/mL on Day 9 (211-324 pg/mL). Mometasone furoate plasma levels appeared to increase and plasma cortisol levels appeared to decrease upon concomitant administration of ketoconazole.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 14 times the MRHD on an AUC basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 9 times the MRHD on an AUC basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not have this effect in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (approximately 8 times the MRHD on an AUC basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 14 times the MRHD on an AUC basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 9 times the MRHD on an AUC basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not have this effect in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (approximately 8 times the MRHD on an AUC basis).

14 CLINICAL STUDIES 14.1 Asthma Adult and Adolescent Patients Aged 12 Years of Age and Older The safety and efficacy of ASMANEX HFA was demonstrated in two randomized, double-blind, placebo- or active-controlled multi-center clinical trials of 12 and 26 weeks' duration, conducted as part of a mometasone furoate/formoterol fumarate 100/5 mcg or 200/5 mcg combination product development program. A total of 1509 patients 12 years of age and older with persistent asthma (mean baseline FEV 1 of 66% to 73% predicted) were evaluated. Trial 1: Clinical Trial with ASMANEX HFA 100 mcg This 26-week, placebo-controlled trial (NCT00383240) conducted as part of a mometasone furoate/formoterol fumarate combination product asthma program evaluated 781 patients 12 years of age and older. Of these patients, 192 patients received ASMANEX HFA 100 mcg and 196 patients received placebo, each administered as 2 inhalations twice daily by metered dose inhalation aerosols. All other maintenance therapies were discontinued. The study included a 2- to 3-week run-in period with ASMANEX HFA 100 mcg, 2 inhalations twice daily. Patients ranged from 12 to 76 years of age, 41% were male and 59% female, and 72% were Caucasian and 28% non-Caucasian. Patients had persistent asthma and were not well controlled on medium dose of inhaled corticosteroids prior to randomization. Mean FEV 1 and mean percent predicted FEV 1 were similar among all treatment groups (2.33 L, 73%). Thirteen (7%) patients receiving ASMANEX HFA 100 mcg and 46 (23%) patients receiving placebo discontinued the study early due to treatment failure. The change in mean trough FEV 1 from baseline to Week 12 compared to placebo was assessed to evaluate the efficacy of ASMANEX HFA 100 mcg. The change from baseline to week 12 in the mean trough FEV 1 was greater among patients receiving ASMANEX HFA 100 mcg 2 inhalations twice daily than among those receiving placebo (treatment difference from placebo 0.12 L and 95% confidence interval [0.05, 0.20]). Clinically judged deteriorations in asthma or reductions in lung function were also assessed to evaluate the efficacy of ASMANEX HFA 100 mcg. Deteriorations in asthma were defined as any of the following: a 20% decrease in FEV 1 ; a 30% decrease in PEF on two or more consecutive days; emergency treatment, hospitalization, or treatment with systemic corticosteroids or other asthma medications not allowed per protocol. Sixty-five (34%) patients who received ASMANEX HFA 100 mcg reported an event compared to 109 (56%) patients who received placebo. Treatment of asthma patients with ASMANEX HFA 100 mcg, two inhalations twice daily also resulted in fewer nocturnal awakenings and improved morning peak flow compared to those who received placebo. Trial 2: Clinical Trial with ASMANEX HFA 200 mcg This 12-week randomized, double-blind, active-controlled trial (NCT00381485) also conducted as part of a mometasone furoate/formoterol fumarate combination product asthma program evaluated a total of 728 patients 12 years of age and older comparing ASMANEX HFA 200 mcg (n=240 patients), mometasone furoate/formoterol fumarate 200 mcg/5 mcg (n=255 patients), and mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=233 patients), each administered as 2 inhalations twice daily by metered dose inhalation aerosols. All other maintenance therapies were discontinued. This trial included a 2- to 3-week run-in period with ASMANEX HFA 200 mcg, 2 inhalations twice daily.

tients), and mometasone furoate/formoterol fumarate 100 mcg/5 mcg (n=233 patients), each administered as 2 inhalations twice daily by metered dose inhalation aerosols. All other maintenance therapies were discontinued. This trial included a 2- to 3-week run-in period with ASMANEX HFA 200 mcg, 2 inhalations twice daily. Patients had persistent asthma and were uncontrolled on high-dose inhaled corticosteroids prior to study entry. Patients ranged from 12 to 84 years of age, 44% were male and 56% female, and 89% were Caucasian and 11% non-Caucasian. Mean FEV 1 and mean percent predicted FEV 1 values were similar among all treatment groups (2.05 L, 66%). The number of patients who discontinued the trial early due to treatment failure were 11 (5%) in the mometasone furoate/formoterol fumarate 100 mcg/5 mcg group, 8 (3%) in the mometasone furoate/formoterol fumarate 200 mcg/5 mcg group, and 13 (5%) in the ASMANEX HFA 200 mcg group. In order to assess the added benefit of a higher dose of mometasone in the 200 mcg/actuation mometasone furoate product compared to the lower dose 100 mcg/actuation product, trough FEV 1 at 12 weeks was compared between the combination mometasone furoate/formoterol fumarate 200 mcg/5 mcg and 100 mcg/5 mcg treatment groups as a secondary endpoint. Improvement in trough FEV 1 from baseline to week 12 in patients who received mometasone furoate 200 mcg in combination with formoterol fumarate 5 mcg was numerically greater than among patients who received mometasone furoate 100 mcg in combination with formoterol fumarate 5 mcg (treatment difference of 0.05 L and 95% confidence interval [-0.02, 0.10]). Other Studies in Adult and Adolescent Patients In addition to Trial 1 and Trial 2, the safety and efficacy of mometasone furoate MDI 100 mcg and 200 mcg (each administered as 2 inhalations, twice daily), in comparison to placebo were demonstrated in two other 12-week, placebo-controlled trials which evaluated the mean change in FEV 1 from baseline as a primary endpoint. A 26-week trial (NCT00383552) also evaluated the same endpoint with a lower dose of mometasone furoate MDI. Pediatric Patients Aged 5 to Less Than 12 Years The safety and efficacy of ASMANEX HFA were demonstrated in a 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in a total of 583 patients aged 5 to less than 12 years with persistent asthma (mean baseline FEV 1 of 79%-predicted) who had been using a low-to-medium dose of ICS with or without LABA for at least 12 weeks prior to study entry. After an approximate 2-week run-in period, subjects were randomized to ASMANEX HFA 50 mcg dose (administered as two inhalations, twice daily), two other doses of ASMANEX HFA, ASMANEX dry-powder inhaler (DPI) or placebo. Patients were 60% male, 71% were Caucasian, and 13% were aged 5 to 6 years old. Primary endpoint results show that after 12 weeks of treatment, ASMANEX HFA 50 mcg (administered as two inhalations, twice daily) was statistically superior to placebo with respect to the improvement from baseline in AM pre-dose percent predicted FEV 1 at the end of the dosing interval (6.29%, 95% CI: 3.05, 9.53).

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied ASMANEX HFA is available in three strengths and supplied in the following package size (TABLE 3): TABLE 3 Package NDC Strength Identifier (Color Band) Included on the outer carton, actuator, and canister labels. ASMANEX HFA 50 mcg 120 metered actuations 78206-111-01 Orange ASMANEX HFA 100 mcg 120 metered actuations 78206-112-01 Green ASMANEX HFA 200 mcg 120 metered actuations 78206-113-01 Blue Each strength is supplied as a pressurized aluminum canister that has a blue plastic actuator integrated with a dose counter and a pink dust cap. Each canister has a net fill weight of 13 grams. Each inhaler is placed into a carton. Each carton contains 1 inhaler. Initially the dose counter will display "124" actuations. After the initial priming with 4 actuations, the dose counter will read "120" and the inhaler is now ready for use. 16.2 Storage and Handling Only use the ASMANEX HFA canister with the ASMANEX HFA actuator. Do not use the ASMANEX HFA actuator with any other inhalation drug product. Do not use actuators from other products with the ASMANEX HFA canister. Do not remove the canister from the actuator because the correct amount of medication may not be discharged; the dose counter may not function properly; reinsertion may cause the dose counter to count down by 1 and discharge a puff. The correct amount of medication in each inhalation cannot be ensured after the labeled number of actuations from the canister has been used, even though the inhaler may not feel completely empty and may continue to operate. Discard the inhaler when the labeled number of actuations has been used (the dose counter will read "0"). Store at controlled room temperature 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. After priming, store the inhaler with the mouthpiece down or in a horizontal position. For best results, keep the canister at room temperature before use. Shake well and remove the cap from the mouthpiece of the actuator before using. Keep out of reach of children. Avoid spraying in eyes. Contents Under Pressure: Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator.

<table width="75%" ID="table4"><caption>TABLE 3</caption><col width="40%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><col width="30%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Package</th><th styleCode="Rrule">NDC</th><th styleCode="Rrule">Strength Identifier (Color Band)<footnote>Included on the outer carton, actuator, and canister labels.</footnote></th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">ASMANEX HFA 50 mcg 120 metered actuations</td><td styleCode="Rrule">78206-111-01</td><td styleCode="Rrule">Orange</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">ASMANEX HFA 100 mcg 120 metered actuations</td><td styleCode="Rrule">78206-112-01</td><td styleCode="Rrule">Green</td></tr><tr><td styleCode="Lrule Rrule">ASMANEX HFA 200 mcg 120 metered actuations</td><td styleCode="Rrule">78206-113-01</td><td styleCode="Rrule">Blue</td></tr></tbody></table>

16.2 Storage and Handling Only use the ASMANEX HFA canister with the ASMANEX HFA actuator. Do not use the ASMANEX HFA actuator with any other inhalation drug product. Do not use actuators from other products with the ASMANEX HFA canister. Do not remove the canister from the actuator because the correct amount of medication may not be discharged; the dose counter may not function properly; reinsertion may cause the dose counter to count down by 1 and discharge a puff. The correct amount of medication in each inhalation cannot be ensured after the labeled number of actuations from the canister has been used, even though the inhaler may not feel completely empty and may continue to operate. Discard the inhaler when the labeled number of actuations has been used (the dose counter will read "0"). Store at controlled room temperature 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. After priming, store the inhaler with the mouthpiece down or in a horizontal position. For best results, keep the canister at room temperature before use. Shake well and remove the cap from the mouthpiece of the actuator before using. Keep out of reach of children. Avoid spraying in eyes. Contents Under Pressure: Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Not for Acute Symptoms Advise patients that ASMANEX HFA is not indicated to relieve acute asthma symptoms, and extra doses should not be used for that purpose. ASMANEX HFA is not a bronchodilator and should not be used to treat status asthmaticus or to relieve acute asthma symptoms. Treat acute asthma symptoms with an inhaled, short-acting beta 2 -agonist such as albuterol. Prescribe the patient with such medication and instruct the patient on how to use it [see Warnings and Precautions (5.1) ]. Instruct patients to seek medical attention immediately if they experience any of the following: If their symptoms worsen Significant decrease in lung function as outlined by the physician If they need more inhalations of a short-acting beta 2 -agonist than usual Advise patients not to increase the dose or frequency of ASMANEX HFA. Do not exceed the daily dosage of ASMANEX HFA two inhalations twice daily. If they miss a dose, instruct patients to take their next dose at the same time they normally do. Advise patients not to stop or reduce ASMANEX HFA therapy without physician/provider guidance since symptoms may recur after discontinuation. Local Effects Advise patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with ASMANEX HFA therapy, but at times therapy with ASMANEX HFA may need to be temporarily interrupted under close medical supervision. After dosing, advise patients to rinse their mouth with water and spit out contents without swallowing [see Warnings and Precautions (5.2) ]. Immunosuppression Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physician without delay. Inform patients of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex [see Warnings and Precautions (5.3) ]. Hypercorticism and Adrenal Suppression Advise patients that ASMANEX HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, instruct patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Instruct patients to slowly taper from systemic corticosteroids if transferring to ASMANEX HFA [see Warnings and Precautions (5.4 and 5.5) ]. Reduction in Bone Mineral Density Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk and should be monitored and, where appropriate, be treated for this condition [see Warnings and Precautions (5.9) ]. Reduced Growth Velocity Inform patients that orally inhaled corticosteroids, including ASMANEX HFA, may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of pediatric patients taking corticosteroids by any route [see Warnings and Precautions (5.10) ]. Glaucoma and Cataracts Advise patients that long-term use of inhaled corticosteroids may increase the risk of some eye problems (glaucoma or cataracts); consider regular eye examinations [see Warnings and Precautions (5.11) ].

ediatric patients taking corticosteroids by any route [see Warnings and Precautions (5.10) ]. Glaucoma and Cataracts Advise patients that long-term use of inhaled corticosteroids may increase the risk of some eye problems (glaucoma or cataracts); consider regular eye examinations [see Warnings and Precautions (5.11) ]. Hypersensitivity Reactions Including Anaphylaxis Advise patients that hypersensitivity reactions, such as urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reaction, may occur after administration of ASMANEX HFA. Instruct patients to discontinue ASMANEX HFA if such reactions occur [see Warnings and Precautions (5.8) ]. Use Daily for Best Effect Advise patients to use ASMANEX HFA at regular intervals, since its effectiveness depends on regular use. Maximum benefit may not be achieved for 1 week or longer after starting treatment. If symptoms do not improve after 2 weeks of therapy or if the condition worsens, instruct patients to contact their physician. Instructions for Use Instruct patients regarding the following: Read the Patient Information before use and follow the Instructions for Use carefully. Remind patients to: Remove the cap from the mouthpiece of the actuator before use. After dosing, rinse their mouth with water and spit out contents without swallowing. This will help reduce the risk of oropharyngeal candidiasis. Not remove the canister from the actuator. Not wash inhaler in water. The mouthpiece should be cleaned using a dry wipe after every 7 days of use.

Manufactured for: Organon LLC, a subsidiary of ORGANON & Co., Jersey City, NJ 07302, USA Manufactured by: Kindeva Drug Delivery Limited, Loughborough, United Kingdom. For patent information: www.organon.com/our-solutions/patent/ © 2025 Organon group of companies. All rights reserved. uspi-og0887-ao-2506r001 Manufactured for: Organon LLC, a subsidiary of ORGANON & Co., Jersey City, NJ 07302, USA Manufactured by: Kindeva Drug Delivery Limited, Loughborough, United Kingdom. For patent information: www.organon.com/our-solutions/patent/ The trademarks depicted herein are owned by their respective companies. © 2025 Organon group of companies. All rights reserved. Revised: 6/2025 usppi-og0887-ao-2506r001

Patient Information ASMANEX ® HFA (AZ-ma-neks) 50 mcg ASMANEX ® HFA 100 mcg ASMANEX ® HFA 200 mcg (mometasone furoate) Inhalation Aerosol This Patient Information has been approved by the U.S. Food and Drug Administration. Revised Date: 6/2025 What is ASMANEX HFA? ASMANEX HFA is an inhaled corticosteroid (ICS) prescription medicine used as maintenance treatment for the prevention and control of asthma symptoms in people 5 years of age and older. ASMANEX HFA is not used to treat sudden severe symptoms of asthma. ASMANEX HFA should not be used as a rescue inhaler. It is not known if ASMANEX HFA is safe and effective in children less than 5 years of age. Who should not use ASMANEX HFA? Do not use ASMANEX HFA: to treat sudden severe symptoms of asthma. if you are allergic to mometasone furoate or any of the ingredients in ASMANEX HFA. See the end of this Patient Information leaflet for a complete list of ingredients in ASMANEX HFA. What should I tell my doctor before and during treatment with ASMANEX HFA? Before you use ASMANEX HFA, tell your healthcare provider if you: have liver problems. have osteoporosis. have an immune system problem. have eye problems such as increased pressure in the eye, glaucoma, cataracts, blurred vision, or other changes in your vision. are allergic to any medicines. are exposed to chickenpox or measles. have or had tuberculosis (TB). have any other medical problems. are pregnant or planning to become pregnant. It is not known if ASMANEX HFA may harm your unborn baby. are breastfeeding. It is not known if ASMANEX HFA passes into your breast milk and if it can harm your baby. You and your healthcare provider should decide if you will either take ASMANEX HFA or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. ASMANEX HFA may affect the way other medicines work, and other medicines may affect how ASMANEX HFA works. Especially, tell your healthcare provider if you take antifungal medicines, antibiotic medicines, or anti-HIV medicines such as: ritonavir atazanavir cobicistat-containing products ketoconazole clarithromycin nefazodone saquinavir nelfinavir telithromycin indinavir itraconazole Ask your healthcare provider if you are not sure if any of your medicines are the kinds listed above. For some medicines (including medicines for HIV such as ritonavir, cobicistat-containing products, and certain antifungals and antibiotics) your doctor may wish to monitor you carefully. Know the medicines you take. Keep a list and show it to your healthcare provider and pharmacist each time you get a new medicine. How should I use ASMANEX HFA? Read the step-by-step instructions for using ASMANEX HFA in the Instructions for Use. Use ASMANEX HFA exactly as prescribed. Do not use ASMANEX HFA more often than prescribed. You must use ASMANEX HFA regularly. It may take 1 week or longer after you start using ASMANEX HFA for your asthma symptoms to get better. Do not stop using ASMANEX HFA even if you are feeling better, unless your healthcare provider tells you to. Do not change or stop using ASMANEX HFA or other asthma medicines used to control or treat your breathing problems unless told to do so by your healthcare provider. Your healthcare provider will change your medicines as needed. ASMANEX HFA comes in 3 strengths. Your healthcare provider has prescribed the strength that is best for you.

stop using ASMANEX HFA or other asthma medicines used to control or treat your breathing problems unless told to do so by your healthcare provider. Your healthcare provider will change your medicines as needed. ASMANEX HFA comes in 3 strengths. Your healthcare provider has prescribed the strength that is best for you. Pay attention to the differences between ASMANEX HFA and your other inhaled medicines, including their prescribed use and the way they look. For children aged 5 to less than 12 years, use ASMANEX HFA 50 mcg. For adults and adolescents 12 years of age and older, use ASMANEX HFA 100 mcg or 200 mcg. Take ASMANEX HFA every day, with 2 puffs in the morning and 2 puffs in the evening. If you miss a dose of ASMANEX HFA, skip your missed dose and take your next dose at your regular time. Do not take ASMANEX HFA more often or use more puffs than you have been prescribed. If you take more ASMANEX HFA than your healthcare provider has prescribed, call your healthcare provider right away. ASMANEX HFA does not relieve sudden asthma symptoms. Always have a rescue inhaler with you to treat sudden symptoms. Use your rescue inhaler if you have breathing problems between doses of ASMANEX HFA. If you do not have a rescue inhaler, call your healthcare provider to have a rescue inhaler prescribed for you. Do not use the ASMANEX HFA canister or actuator with any other medicines. Do not use any other medicine canister or actuator with ASMANEX HFA. Rinse your mouth with water after each dose (2 puffs) of ASMANEX HFA. Spit out the water. Do not swallow it. This will help to lessen the chance of getting a yeast infection (thrush) in your mouth and throat. Do not spray ASMANEX HFA in your eyes. If you accidentally get ASMANEX HFA in your eyes, rinse your eyes with water and if redness or irritation continues, call your healthcare provider. Call your healthcare provider or get medical care right away if: your breathing problems worsen with ASMANEX HFA you need to use your rescue inhaler more often than usual your rescue inhaler does not work as well for you at relieving symptoms you need to use 4 or more inhalations of your rescue inhaler for 2 or more days in a row you use 1 whole canister of your rescue inhaler within 8 weeks your peak flow meter results decrease. Your healthcare provider will tell you the numbers that are right for you you have asthma and your symptoms do not improve after using ASMANEX HFA regularly for 1 to 2 weeks What are the possible side effects of ASMANEX HFA? ASMANEX HFA can cause serious side effects, including Thrush in your mouth and throat. You may develop thrush, a yeast infection (Candida albicans), in your mouth or throat. After each dose (2 puffs) of ASMANEX HFA, rinse your mouth with water. Spit out the water. Do not swallow it. This will help to prevent thrush in your mouth or throat. Immune system effects and a higher chance for infections. Tell your healthcare provider about any signs of infection such as: fever feeling tired body aches vomiting pain nausea chills Adrenal insufficiency that can lead to death can happen when you stop taking oral corticosteroid medicines and start using inhaled corticosteroid medicines. Adrenal insufficiency can also happen in people who take higher doses of ASMANEX HFA than recommended over a long period of time. When your body is under stress such as from fever, trauma (such as a car accident), infection, or surgery, adrenal insufficiency can get worse. Symptoms of adrenal insufficiency include: feeling tired or exhausted (fatigue) weakness lack of energy nausea and vomiting low blood pressure (hypotension) dizziness or feeling faint Increased wheezing right after taking ASMANEX HFA. Always have a rescue inhaler with you to treat sudden wheezing. Serious allergic reactions.

ms of adrenal insufficiency include: feeling tired or exhausted (fatigue) weakness lack of energy nausea and vomiting low blood pressure (hypotension) dizziness or feeling faint Increased wheezing right after taking ASMANEX HFA. Always have a rescue inhaler with you to treat sudden wheezing. Serious allergic reactions. Stop taking ASMANEX HFA and call your healthcare provider or get emergency medical care right away if you get any of the following symptoms of a serious allergic reaction: rash hives swelling, including swelling of the face, mouth, and tongue breathing problems Lower bone mineral density. This may be a problem for people who already have a higher chance for low bone density (osteoporosis). Slowed growth in children. A child's growth should be checked often. Eye problems including glaucoma, cataracts, and blurred vision. You should have regular eye exams while using ASMANEX HFA. The most common side effects reported while using ASMANEX HFA include: inflammation of the nose and throat (nasopharyngitis) inflammation of the sinuses (sinusitis) headache bronchitis flu infection (influenza) Other side effects: Worsening asthma or sudden asthma attacks have been reported with the use of inhaled mometasone furoate. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the side effects with ASMANEX HFA. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store ASMANEX HFA? Store ASMANEX HFA at room temperature between 68°F to 77°F (20°C to 25°C). After priming, store the inhaler with the mouthpiece down or sideways. The contents of your ASMANEX HFA are under pressure. Do not puncture. Do not use or store near heat or open flame. Storage above 120°F may cause the canister to burst. Do not throw container into fire or incinerator. Keep ASMANEX HFA and all medicines out of the reach of children. General Information about the safe and effective use of ASMANEX HFA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ASMANEX HFA for a condition for which it was not prescribed. Do not give your ASMANEX HFA to other people, even if they have the same condition that you have. It may harm them. This Patient Information leaflet summarizes the most important information about ASMANEX HFA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ASMANEX HFA that was written for healthcare professionals. For more information about ASMANEX HFA go to www.ASMANEX.com, or to report side effects call 1-844-674-3200. What are the ingredients in ASMANEX HFA? Active ingredient: mometasone furoate Inactive ingredients: hydrofluoroalkane (HFA-227: 1,1,1,2,3,3,3-heptafluoropropane), ethanol and oleic acid

<table width="100%"><col width="16%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><col width="14%" align="left" valign="top"/><thead><tr><th colspan="7" align="center" styleCode="Lrule Rrule">Patient Information ASMANEX^&#xAE; HFA (AZ-ma-neks) 50 mcg ASMANEX^&#xAE; HFA 100 mcg ASMANEX^&#xAE; HFA 200 mcg (mometasone furoate) Inhalation Aerosol</th></tr></thead><tfoot><tr><td colspan="5" align="left" valign="top">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td colspan="2" align="right" valign="top">Revised Date: 6/2025</td></tr></tfoot><tbody><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">What is ASMANEX HFA?</content> ASMANEX HFA is an inhaled corticosteroid (ICS) prescription medicine used as maintenance treatment for the prevention and control of asthma symptoms in people 5 years of age and older. <list><item>ASMANEX HFA is not used to treat sudden severe symptoms of asthma.</item><item>ASMANEX HFA should not be used as a rescue inhaler.</item><item>It is not known if ASMANEX HFA is safe and effective in children less than 5 years of age.</item></list></td></tr><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">Who should not use ASMANEX HFA? Do not use ASMANEX HFA: </content><list><item>to treat sudden severe symptoms of asthma.</item><item>if you are allergic to mometasone furoate or any of the ingredients in ASMANEX HFA. See the end of this Patient Information leaflet for a complete list of ingredients in ASMANEX HFA.</item></list></td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">What should I tell my doctor before and during treatment with ASMANEX HFA? Before you use ASMANEX HFA, tell your healthcare provider if you:</content><list><item>have liver problems.</item><item>have osteoporosis.</item><item>have an immune system problem.</item><item>have eye problems such as increased pressure in the eye, glaucoma, cataracts, blurred vision, or other changes in your vision.</item><item>are allergic to any medicines.</item><item>are exposed to chickenpox or measles.</item><item>have or had tuberculosis (TB).</item><item>have any other medical problems.</item><item>are pregnant or planning to become pregnant. It is not known if ASMANEX HFA may harm your unborn baby.</item><item>are breastfeeding. It is not known if ASMANEX HFA passes into your breast milk and if it can harm your baby. You and your healthcare provider should decide if you will either take ASMANEX HFA or breastfeed.</item></list><content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. ASMANEX HFA may affect the way other medicines work, and other medicines may affect how ASMANEX HFA works.

breastfeed.</item></list><content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. ASMANEX HFA may affect the way other medicines work, and other medicines may affect how ASMANEX HFA works. <content styleCode="bold">Especially, tell your healthcare provider if you take antifungal medicines, antibiotic medicines, or anti-HIV medicines such as:</content></td></tr><tr><td styleCode="Lrule"><list><item>ritonavir</item><item>atazanavir</item><item>cobicistat-containing products</item></list></td><td><list><item>ketoconazole</item><item>clarithromycin</item></list></td><td><list><item>nefazodone</item><item>saquinavir</item></list></td><td><list><item>nelfinavir</item><item>telithromycin</item></list></td><td colspan="3" styleCode="Rrule"><list><item>indinavir</item><item>itraconazole</item></list></td></tr><tr styleCode="Botrule"><td colspan="7" styleCode="Lrule Rrule">Ask your healthcare provider if you are not sure if any of your medicines are the kinds listed above. For some medicines (including medicines for HIV such as ritonavir, cobicistat-containing products, and certain antifungals and antibiotics) your doctor may wish to monitor you carefully. Know the medicines you take. Keep a list and show it to your healthcare provider and pharmacist each time you get a new medicine.</td></tr><tr styleCode="Botrule"><td colspan="7" styleCode="Lrule Rrule"><content styleCode="bold">How should I use ASMANEX HFA? Read the step-by-step instructions for using ASMANEX HFA in the Instructions for Use.</content><list><item>Use ASMANEX HFA exactly as prescribed. <content styleCode="bold">Do not</content> use ASMANEX HFA more often than prescribed.</item><item>You must use ASMANEX HFA regularly. It may take 1 week or longer after you start using ASMANEX HFA for your asthma symptoms to get better. Do not stop using ASMANEX HFA even if you are feeling better, unless your healthcare provider tells you to.</item><item><content styleCode="bold">Do not</content> change or stop using ASMANEX HFA or other asthma medicines used to control or treat your breathing problems unless told to do so by your healthcare provider. Your healthcare provider will change your medicines as needed.</item><item>ASMANEX HFA comes in 3 strengths. Your healthcare provider has prescribed the strength that is best for you. Pay attention to the differences between ASMANEX HFA and your other inhaled medicines, including their prescribed use and the way they look.</item><item>For children aged 5 to less than 12 years, use ASMANEX HFA 50 mcg.</item><item>For adults and adolescents 12 years of age and older, use ASMANEX HFA 100 mcg or 200 mcg.</item><item>Take ASMANEX HFA every day, with 2 puffs in the morning and 2 puffs in the evening.</item><item>If you miss a dose of ASMANEX HFA, skip your missed dose and take your next dose at your regular time. Do not take ASMANEX HFA more often or use more puffs than you have been prescribed.</item><item>If you take more ASMANEX HFA than your healthcare provider has prescribed, call your healthcare provider right away. </item><item>ASMANEX HFA does not relieve sudden asthma symptoms. Always have a rescue inhaler with you to treat sudden symptoms. Use your rescue inhaler if you have breathing problems between doses of ASMANEX HFA. If you do not have a rescue inhaler, call your healthcare provider to have a rescue inhaler prescribed for you. </item><item>Do not use the ASMANEX HFA canister or actuator with any other medicines. Do not use any other medicine canister or actuator with ASMANEX HFA.</item><item>Rinse your mouth with water after each dose (2 puffs) of ASMANEX HFA. Spit out the water. Do not swallow it.

o have a rescue inhaler prescribed for you. </item><item>Do not use the ASMANEX HFA canister or actuator with any other medicines. Do not use any other medicine canister or actuator with ASMANEX HFA.</item><item>Rinse your mouth with water after each dose (2 puffs) of ASMANEX HFA. Spit out the water. Do not swallow it. This will help to lessen the chance of getting a yeast infection (thrush) in your mouth and throat.</item><item>Do not spray ASMANEX HFA in your eyes. If you accidentally get ASMANEX HFA in your eyes, rinse your eyes with water and if redness or irritation continues, call your healthcare provider.</item><item><content styleCode="bold">Call your healthcare provider or get medical care right away if:</content><list><item>your breathing problems worsen with ASMANEX HFA</item><item>you need to use your rescue inhaler more often than usual </item><item>your rescue inhaler does not work as well for you at relieving symptoms </item><item>you need to use 4 or more inhalations of your rescue inhaler for 2 or more days in a row </item><item>you use 1 whole canister of your rescue inhaler within 8 weeks </item><item>your peak flow meter results decrease. Your healthcare provider will tell you the numbers that are right for you</item><item>you have asthma and your symptoms do not improve after using ASMANEX HFA regularly for 1 to 2 weeks </item></list></item></list></td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">What are the possible side effects of ASMANEX HFA? ASMANEX HFA can cause serious side effects, including</content></td></tr><tr><td colspan="7" styleCode="Lrule Rrule"><list><item><content styleCode="bold">Thrush in your mouth and throat.</content> You may develop thrush, a yeast infection (Candida albicans), in your mouth or throat. After each dose (2 puffs) of ASMANEX HFA, rinse your mouth with water. Spit out the water. Do not swallow it. This will help to prevent thrush in your mouth or throat.</item><item><content styleCode="bold">Immune system effects and a higher chance for infections.</content> Tell your healthcare provider about any signs of infection such as:</item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>fever</item></list></td><td><list listType="unordered" styleCode="Circle"><item>feeling tired</item></list></td><td><list listType="unordered" styleCode="Circle"><item>body aches</item></list></td><td><list listType="unordered" styleCode="Circle"><item>vomiting</item></list></td><td><list listType="unordered" styleCode="Circle"><item>pain</item></list></td><td><list listType="unordered" styleCode="Circle"><item>nausea</item></list></td><td styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>chills</item></list></td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><list><item><content styleCode="bold">Adrenal insufficiency that can lead to death</content> can happen when you stop taking oral corticosteroid medicines and start using inhaled corticosteroid medicines. Adrenal insufficiency can also happen in people who take higher doses of ASMANEX HFA than recommended over a long period of time. When your body is under stress such as from fever, trauma (such as a car accident), infection, or surgery, adrenal insufficiency can get worse.

start using inhaled corticosteroid medicines. Adrenal insufficiency can also happen in people who take higher doses of ASMANEX HFA than recommended over a long period of time. When your body is under stress such as from fever, trauma (such as a car accident), infection, or surgery, adrenal insufficiency can get worse. Symptoms of adrenal insufficiency include:</item></list></td></tr><tr><td colspan="2" valign="top" styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>feeling tired or exhausted (fatigue)</item><item>weakness</item></list></td><td colspan="2"><list listType="unordered" styleCode="Circle"><item>lack of energy</item><item>nausea and vomiting</item></list></td><td colspan="3" styleCode="Rrule"><list listType="unordered" styleCode="Circle"><item>low blood pressure (hypotension)</item><item>dizziness or feeling faint</item></list></td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><list><item><content styleCode="bold">Increased wheezing right after taking ASMANEX HFA.</content> Always have a rescue inhaler with you to treat sudden wheezing.</item><item><content styleCode="bold">Serious allergic reactions. </content>Stop taking ASMANEX HFA and call your healthcare provider or get emergency medical care right away if you get any of the following symptoms of a serious allergic reaction:</item></list></td></tr><tr><td styleCode="Lrule"><list listType="unordered" styleCode="Circle"><item>rash</item></list></td><td><list listType="unordered" styleCode="Circle"><item>hives</item></list></td><td colspan="3"><list listType="unordered" styleCode="Circle"><item>swelling, including swelling of the face, mouth, and tongue</item></list></td><td styleCode="Rrule" colspan="2"><list listType="unordered" styleCode="Circle"><item>breathing problems</item></list></td></tr><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><list><item><content styleCode="bold">Lower bone mineral density. </content>This may be a problem for people who already have a higher chance for low bone density (osteoporosis).</item><item><content styleCode="bold">Slowed growth in children. </content>A child&apos;s growth should be checked often.</item><item><content styleCode="bold">Eye problems including glaucoma, cataracts, and blurred vision. </content>You should have regular eye exams while using ASMANEX HFA.</item></list></td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">The most common side effects reported while using ASMANEX HFA include:</content></td></tr><tr><td styleCode="Lrule" colspan="3"><list><item>inflammation of the nose and throat (nasopharyngitis)</item><item>inflammation of the sinuses (sinusitis)</item></list></td><td colspan="2"><list><item>headache</item><item>bronchitis</item></list></td><td styleCode="Rrule" colspan="2"><list><item>flu infection (influenza)</item></list></td></tr><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">Other side effects: </content>Worsening asthma or sudden asthma attacks have been reported with the use of inhaled mometasone furoate. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the side effects with ASMANEX HFA. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td></tr><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">How should I store ASMANEX HFA?</content><list><item>Store ASMANEX HFA at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item>After priming, store the inhaler with the mouthpiece down or sideways.

="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">How should I store ASMANEX HFA?</content><list><item>Store ASMANEX HFA at room temperature between 68&#xB0;F to 77&#xB0;F (20&#xB0;C to 25&#xB0;C).</item><item>After priming, store the inhaler with the mouthpiece down or sideways. </item><item>The contents of your ASMANEX HFA are under pressure. <content styleCode="bold">Do not</content> puncture. <content styleCode="bold">Do not</content> use or store near heat or open flame. Storage above 120&#xB0;F may cause the canister to burst.</item><item><content styleCode="bold">Do not</content> throw container into fire or incinerator.</item><item><content styleCode="bold">Keep ASMANEX HFA and all medicines out of the reach of children.</content></item></list></td></tr><tr styleCode="Botrule"><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">General Information about the safe and effective use of ASMANEX HFA.</content> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ASMANEX HFA for a condition for which it was not prescribed. Do not give your ASMANEX HFA to other people, even if they have the same condition that you have. It may harm them. This Patient Information leaflet summarizes the most important information about ASMANEX HFA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ASMANEX HFA that was written for healthcare professionals. For more information about ASMANEX HFA go to www.ASMANEX.com, or to report side effects call 1-844-674-3200.</td></tr><tr><td colspan="7" valign="top" styleCode="Lrule Rrule"><content styleCode="bold">What are the ingredients in ASMANEX HFA?</content> Active ingredient: mometasone furoate Inactive ingredients: hydrofluoroalkane (HFA-227: 1,1,1,2,3,3,3-heptafluoropropane), ethanol and oleic acid</td></tr></tbody></table>

Instructions for Use ASMANEX ® HFA (AZ-ma-neks) 50 mcg ASMANEX ® HFA 100 mcg ASMANEX ® HFA 200 mcg (mometasone furoate) Inhalation Aerosol Read these Instructions for Use before you start using ASMANEX HFA and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or your treatment. The parts of your ASMANEX HFA: There are 2 main parts to your ASMANEX HFA inhaler: the metal canister that holds the medicine and the blue plastic actuator that sprays the medicine from the canister. The inhaler also has a pink cap that covers the mouthpiece of the actuator (see Figure 1 ) . The cap from the mouthpiece must be removed before use. The inhaler contains "120" actuations (puffs). Figure 1 The inhaler comes with a dose counter located on the plastic actuator (see Figure 1 ). The counter display will show the number of actuations (puffs) of medicine remaining. The first time you use ASMANEX HFA the dose counter will show "124" actuations remaining. Each time you press the canister, a puff of medicine is released and the counter will count down by 1 . The counter will stop counting at 0 . Important Information: Use ASMANEX HFA exactly as your healthcare provider tells you to. Adults may assist children with using ASMANEX HFA as prescribed. Children may use ASMANEX HFA with or without a spacer device. Remove the cap from the mouthpiece of the actuator before using ASMANEX HFA. Do not remove the canister from the actuator because: you may not receive the correct amount of medication. the dose counter may not function properly. if you try to insert the canister back into the actuator this may cause the dose counter to count down by 1 and may discharge a puff. Use the ASMANEX HFA canister only with the actuator supplied with the product. Do not use parts of the ASMANEX HFA inhaler with parts from any other inhalation medicine. Before using your ASMANEX HFA: Remove the cap from the mouthpiece of the actuator before using ASMANEX HFA (see Figure 2 ) . Check the mouthpiece for objects before use. Make sure the canister is fully inserted into the actuator. Figure 2 Priming your ASMANEX HFA Inhaler: Before you use ASMANEX HFA for the first time, you must prime the inhaler. 1. To prime the inhaler, hold it in the upright position away from your face, and press down firmly and fully on the top of the canister until it stops moving in the actuator. Do this 4 times to release a total of 4 actuations (puffs) into the air. 2. Shake the inhaler well before each of the priming actuations. After priming 4 times, the dose counter should read "120" . 3. If you do not use your ASMANEX HFA for more than 5 days, you will need to prime it again before use. Using your ASMANEX HFA: 4. Confirm that the strength indicated on the actuator and canister labels matches the prescribed dosage. 5. Remove the cap from the mouthpiece of the actuator (see Figure 3 ) . Check the mouthpiece for objects before use. Make sure the canister is fully inserted into the actuator. 6. Shake the inhaler well before each use. 7. Breathe out as fully as you comfortably can through your mouth. Push out as much air from your lungs as possible. Hold the inhaler in the upright position and place the mouthpiece into your mouth (see Figure 4 ) . Close your lips around the mouthpiece. Figure 3 Figure 4 8. Take a deep breath (inhale) in slowly through your mouth.

as fully as you comfortably can through your mouth. Push out as much air from your lungs as possible. Hold the inhaler in the upright position and place the mouthpiece into your mouth (see Figure 4 ) . Close your lips around the mouthpiece. Figure 3 Figure 4 8. Take a deep breath (inhale) in slowly through your mouth. While doing this, press down firmly and fully on the top of the canister until it stops moving in the actuator. Take your finger off the canister. 9. When you have finished breathing in, hold your breath as long as you comfortably can, up to 10 seconds . Then remove the inhaler from your mouth and breathe out through your nose, while keeping your lips closed. 10. Wait at least 30 seconds to take your second puff of ASMANEX HFA. 11. Shake the inhaler well again and repeat steps 6 through 8 to take your second puff of ASMANEX HFA. After using your ASMANEX HFA inhaler: 12. Replace the cap over the mouthpiece right away after use (see Figure 5 ) . Figure 5 13. After you finish taking ASMANEX HFA ( 2 puffs), rinse your mouth with water. Reading the counter: The dose counter identifies the number of inhalations (puffs) left in your inhaler (see Figure 6 ) . The counter will count down each time you release a puff of medicine (either when preparing your ASMANEX HFA inhaler for use or when using the medicine). Figure 6 When to replace your ASMANEX HFA: It is important that you pay attention to the number of inhalations (puffs) left in your ASMANEX HFA inhaler by reading the counter. When the counter reads "20" , you should refill your prescription or ask your healthcare provider if you need a new prescription for ASMANEX HFA. Throw away ASMANEX HFA after the counter reaches "0" , indicating that you have used the number of actuations on the product label and box. Your inhaler may not feel empty and it may continue to operate, but you will not get the right amount of medicine if you keep using it. Never try to change the numbers on the counter or remove the counter from the actuator. Do not use the inhaler after the expiration date. How to clean your ASMANEX HFA: The mouthpiece should be cleaned using a dry wipe after every 7 days of use. Routine cleaning instructions: Remove the cap off the mouthpiece. Wipe the inside and outside surfaces of the actuator mouthpiece with a clean, dry, lint-free tissue or cloth. Do not wash or put any parts of your inhaler in water. Put the cap back on the mouthpiece after cleaning. Do not remove the canister from the actuator. Do not attempt to unblock the actuator with a sharp object, such as a pin. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

<table width="100%" styleCode="Noautorules"><col width="50%" align="center" valign="bottom"/><col width="50%" align="center" valign="bottom"/><tbody><tr><td><renderMultiMedia referencedObject="MM4" ID="fig3"/></td><td><renderMultiMedia referencedObject="MM5" ID="fig4"/></td></tr><tr><td align="left"><content styleCode="bold"> Figure 3</content></td><td align="center"><content styleCode="bold">Figure 4</content></td></tr></tbody></table>

1 INDICATIONS AND USAGE Mometasone furoate nasal spray is a corticosteroid indicated for: Prophylaxis of Nasal Symptoms of Seasonal Allergic Rhinitis in adult and pediatric patients 12 years of age and older ( 1.1 ) Treatment of Chronic Rhinosinusitis with Nasal Polyps in adult patients 18 years of age and older ( 1.2 ) 1.1 Prophylaxis of Seasonal Allergic Rhinitis Mometasone furoate nasal spray is indicated for the prophylaxis of the nasal symptoms of seasonal allergic rhinitis in adult and pediatric patients 12 years and older. 1.2 Treatment of Chronic Rhinosinusitis with Nasal Polyps Mometasone furoate nasal spray is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients 18 years of age and older.

2 DOSAGE AND ADMINISTRATION For Nasal Use Only Prophylaxis of Seasonal Allergic Rhinitis in Adult and Pediatric Patients 12 Years of Age and Older: 2 sprays in each nostril once daily ( 2.2 ) Treatment of Chronic Rhinosinusitis with Nasal Polyps in Adults (18 yrs. and older): 2 sprays in each nostril twice daily. 2 sprays in each nostril once daily may also be effective in some patients ( 2.3 ) 2.1 Preparation and Administration Administer mometasone furoate nasal spray by the nasal route only. Initial Priming Prior to initial use of mometasone furoate nasal spray, the pump must be primed by actuating ten times or until a fine spray appears. The pump may be stored unused for up to 1 week without repriming. Repriming (as needed) If unused for more than 1 week, reprime by actuating two times, or until a fine spray appears. 2.2 Recommended Dosage for Prophylaxis of Seasonal Allergic Rhinitis The recommended dosage for prophylaxis treatment of nasal symptoms of seasonal allergic rhinitis in adult and pediatric patients 12 years and older is mometasone furoate nasal spray 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg). In patients with a known seasonal allergen that precipitates nasal symptoms of seasonal allergic rhinitis, prophylaxis with 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg) is recommended 2 to 4 weeks prior to the anticipated start of the pollen season. 2.3 Recommended Dosage for Treatment of Chronic Rhinosinusitis with Nasal Polyps The recommended dosage for the treatment of chronic rhinosinusitis with nasal polyps in adults 18 years and older is mometasone furoate nasal spray 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril twice daily (total daily dose of 400 mcg). A dose of 2 sprays (2 sprays deliver a total of 100 mcg of mometasone furoate) in each nostril once daily (total daily dose of 200 mcg) is also effective in some patients.

4 CONTRAINDICATIONS Mometasone furoate nasal spray is contraindicated in patients with known hypersensitivity to mometasone furoate or any of its ingredients [see Warnings and Precautions ( 5.3 ), Description ( 11 )]. Patients with known hypersensitivity to mometasone furoate or any of the ingredients of mometasone furoate nasal spray. ( 4 )

5 WARNINGS AND PRECAUTIONS Epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, impaired wound healing. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma. ( 5.1 ) Glaucoma and cataracts. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use mometasone furoate nasal spray long term. ( 5.2 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) Hypercorticism and adrenal suppression with higher than recommended dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue mometasone furoate nasal spray slowly. ( 5.5 ) Potential reduction in growth velocity in children. Monitor growth routinely in pediatric patients receiving mometasone furoate nasal spray. ( 5.6 , 8.4 ) 5.1 Local Nasal Adverse Reactions Epistaxis Epistaxis was observed more frequently in patients with allergic rhinitis and patients with chronic rhinosinusitis with nasal polyps who received mometasone furoate nasal spray than those who received placebo [see Adverse Reactions ( 6.1 )]. Candida Infection Localized infections of the nose and pharynx with Candida albicans has occurred from nasal administration of mometasone furoate. When such an infection develops, use of mometasone furoate nasal spray should be discontinued and appropriate local or systemic therapy instituted, if needed. Nasal Septum Perforation Instances of nasal septum perforation occurred in patients following the nasal application of corticosteroids, including mometasone furoate nasal spray. As with any long-term topical treatment of the nasal cavity, patients using mometasone furoate nasal spray over several months or longer should be examined periodically for possible changes in the nasal mucosa. Impaired Wound Healing Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septum ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred. 5.2 Glaucoma and Cataracts Glaucoma and cataracts may be reported with systemic and topical (including nasal, inhaled and ophthalmic) corticosteroid use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use mometasone furoate nasal spray long term [see Adverse Reactions ( 6 )]. 5.3 Hypersensitivity Reactions Hypersensitivity reactions including instances of wheezing may occur after the nasal administration of mometasone furoate monohydrate. Discontinue mometasone furoate nasal spray if such reactions occur [ see Contraindications (4) ] . 5.4 Immunosuppression and Risk of Infections Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known.

or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective Prescribing Information for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered. Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infection of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections, or ocular herpes simplex because of the potential for worsening of these infections. 5.5 Hypercorticism and Adrenal Suppression Hypercorticism and adrenal suppression may occur when nasal corticosteroids, including mometasone furoate nasal spray, are used at higher-than-recommended dosages [see Dosage and Administration ( 2 )] or in patients at risk for such effects. If such changes occur, the dosage of mometasone furoate nasal spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy. 5.6 Effect on Growth Corticosteroids, including mometasone furoate nasal spray may cause a reduction in growth velocity when administered to pediatric patients. Routinely, monitor the growth of pediatric patients receiving mometasone furoate nasal spray. To minimize the systemic effects of nasal corticosteroids, including mometasone furoate nasal spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations ( 8.4 )].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Epistaxis, Ulcerations, Candida albicans Infection, Impaired Wound Healing [see Warnings and Precautions ( 5.1 )] Glaucoma and Cataracts [see Warnings and Precautions ( 5.2 )] Immunosuppression and Risk of Infections [see Warnings and Precautions ( 5.4 )] Hypercorticism and Adrenal Suppression, including Growth Reduction [see Warnings and Precautions ( 5.5 , 5.6 ), Use in Specific Populations ( 8.4 )] The most common adverse reactions (incidence ≥5%) included headache, viral infection, pharyngitis, epistaxis and cough. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 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 practice. Allergic Rhinitis Adults and pediatric patients 12 years of age and older In controlled U.S. and international clinical studies, a total of 3,210 adult and pediatric patients 12 years and older with allergic rhinitis received treatment with mometasone furoate nasal spray at doses of 50 to 800 mcg/day. The majority of patients (n=2,103) were treated with 200 mcg/day. A total of 350 adult and pediatric patients 12 years and older have been treated for one year or longer. Adverse reactions did not differ significantly based on age, sex, or race. Four percent or less of patients in clinical trials discontinued treatment because of adverse events and the discontinuation rate was similar for the vehicle and active comparators. All adverse reactions (regardless of relationship to treatment) reported by 5% or more of adult and pediatric patients ages 12 years and older who received mometasone furoate nasal spray, 200 mcg/day vs. placebo and that were more common with mometasone furoate nasal spray than placebo, are displayed in Table 1 below. Table 1: Adult and Pediatric Patients 12 Years and Older – Adverse Reactions from Controlled Clinical Trials in Seasonal Allergic and Perennial Allergic Rhinitis (Percent of Patients Reporting) Mometasone Furoate Nasal Spray 200 mcg (n = 2,103) % Vehicle Placebo (n = 1,671) % Headache 26 22 Viral Infection 14 11 Pharyngitis 12 10 Epistaxis/Blood-Tinged Mucus 11 6 Coughing 7 6 Upper Respiratory Tract Infection 6 2 Dysmenorrhea 5 3 Musculoskeletal Pain 5 3 Sinusitis 5 3 Other adverse reactions which occurred in less than 5% but greater than or equal to 2% of adult and pediatric patients (ages 12 years and older) treated with mometasone furoate nasal spray 200-mcg/day (regardless of relationship to treatment), and more frequently than in the placebo group included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, earache, flu-like symptoms, myalgia, nausea, and rhinitis. Chronic Rhinosinusitis with Nasal Polyps Adults 18 years of age and older In controlled clinical studies, the types of adverse reactions observed in patients with chronic rhinosinusitis with nasal polyps were similar to those observed in patients with allergic rhinitis.

flu-like symptoms, myalgia, nausea, and rhinitis. Chronic Rhinosinusitis with Nasal Polyps Adults 18 years of age and older In controlled clinical studies, the types of adverse reactions observed in patients with chronic rhinosinusitis with nasal polyps were similar to those observed in patients with allergic rhinitis. A total of 594 adult patients (ages 18 to 86 years) received mometasone furoate nasal spray at doses of 200 mcg once or twice daily for up to 4 months for treatment of chronic rhinosinusitis with nasal polyps. The overall incidence of adverse reactions for patients treated with mometasone furoate nasal spray was comparable to patients with the placebo except for epistaxis, which was 9% for 200 mcg once daily, 13% for 200 mcg twice daily, and 5% for the placebo. Nasal ulcers and nasal and oral candidiasis were also reported in patients treated with mometasone furoate nasal spray primarily in patients treated for longer than 4 weeks. 6.2 Post-Marketing Experience The following adverse reactions have been identified during the post-marketing period for mometasone furoate nasal spray: nasal burning and irritation, anaphylaxis and angioedema, disturbances in taste and smell, nasal septal perforation, and vision blurred. Because these 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.

<table frame="box" rules="all"><thead><tr align="center"><td><content styleCode="bold"> </content></td><td align="center"><content styleCode="bold">Mometasone Furoate Nasal Spray</content><content styleCode="bold"> 200 mcg </content><content styleCode="bold"> (n = 2,103)</content><content styleCode="bold"> %</content></td><td><content styleCode="bold">Vehicle Placebo </content><content styleCode="bold"> (n = 1,671)</content><content styleCode="bold"> %</content></td></tr></thead><tbody><tr><td> Headache </td><td align="center"> 26 </td><td align="center"> 22 </td></tr><tr><td> Viral Infection </td><td align="center"> 14 </td><td align="center"> 11 </td></tr><tr><td> Pharyngitis </td><td align="center"> 12 </td><td align="center"> 10 </td></tr><tr><td> Epistaxis/Blood-Tinged Mucus </td><td align="center"> 11 </td><td align="center"> 6 </td></tr><tr><td> Coughing </td><td align="center"> 7 </td><td align="center"> 6 </td></tr><tr><td> Upper Respiratory Tract Infection </td><td align="center"> 6 </td><td align="center"> 2 </td></tr><tr><td> Dysmenorrhea </td><td align="center"> 5 </td><td align="center"> 3 </td></tr><tr><td> Musculoskeletal Pain </td><td align="center"> 5 </td><td align="center"> 3 </td></tr><tr><td> Sinusitis </td><td align="center"> 5 </td><td align="center"> 3 </td></tr></tbody></table>

7 DRUG INTERACTIONS No formal drug-drug interaction studies have been conducted with mometasone furoate nasal spray. Inhibitors of Cytochrome P450 3A4: Studies have shown that mometasone furoate is primarily and extensively metabolized in the liver of all species investigated and undergoes extensive metabolism to multiple metabolites. In vitro studies have confirmed the primary role of cytochrome CYP3A4 in the metabolism of this compound. Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, mometasone furoate and potentially increase the risk for systemic corticosteroid side effects. Caution should be exercised when considering the coadministration of mometasone furoate nasal spray with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Clinical Pharmacology ( 12.3 )]. Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side effects.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Mometasone is minimally absorbed systemically following nasal use, and maternal use is not expected to result in fetal exposure to the drug. Available data from observational studies of mometasone use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies with pregnant mice, rats, or rabbits (subcutaneous, subcutaneous/topical dermal/oral, and topical dermal/oral, respectively), mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data]. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at a dose less than the maximum recommended daily intranasal dose (MRDID) (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure less than the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 10 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at a dose approximately 6 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above).

organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at a dose approximately 30 times of the MRDID (on a mcg/m 2 basis with a maternal oral dose of 700 mcg/kg). At approximately 110 times the MRDID (on a mcg/m 2 basis with a maternal oral dose of 2,800 mcg/kg), most litters were aborted or resorbed. No effects were observed at a dose approximately 6 times the MRDID (on a mcg/m 2 basis with a maternal oral dose of 140 mcg/kg). 8.2 Lactation Risk Summary There are no available data on the presence of mometasone furoate nasal spray in human milk, the effects on the breastfed child, or the effects on milk production. However, mometasone is minimally absorbed systemically by the mother following nasal use, and breastfeeding is not expected to result in exposure of the infant to mometasone. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mometasone furoate nasal spray and any potential adverse effects on the breastfed infant from mometasone furoate nasal spray or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of mometasone furoate nasal spray for prophylaxis of the nasal symptoms of seasonal allergic rhinitis in pediatric patients 12 years of age and older have been established [see Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.1 )]. Use of mometasone furoate nasal spray forthis indication is supported by evidence from controlled trials in adult and pediatric patients 12 years of age and older [see Clinical Studies ( 14.1 )]. The safety and effectiveness of mometasone furoate nasal spray for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients less than 18 years of age have not been established. Effectiveness was not demonstrated in one 4-month trial conducted to evaluate the safety and efficacy of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients 6 to 17 years of age. The primary objective of the study was to evaluate safety; efficacy parameters were collected as secondary endpoints. A total of 127 patients with chronic rhinosinusitis with nasal polyps were randomized to placebo or mometasone furoate nasal spray 100 mcg once or twice daily (patients 6 to 11 years of age) or 200 mcg once or twice daily (patients 12 to 17 years of age). The results of this trial did not support the efficacy of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients. The adverse reactions reported in this trial were similar to the adverse reactions reported in patients 18 years of age and older with chronic rhinosinusitis with nasal polyps. Effect on Growth Controlled clinical studies have shown nasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown.

ting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch up" growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving nasal corticosteroids, including mometasone furoate nasal spray, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of nasal corticosteroids, including mometasone furoate nasal spray, each patient should be titrated to his/her lowest effective dose. A clinical study to assess the effect of mometasone furoate nasal spray (100 mcg total daily dose) on growth velocity has been conducted in pediatric patients 3 to 9 years of age with allergic rhinitis. No statistically significant effect on growth velocity was observed for mometasone furoate nasal spray compared to placebo following one year of treatment. No evidence of clinically relevant HPA axis suppression was observed following a 30-minute cosyntropin infusion. The potential of mometasone furoate nasal spray to cause growth suppression in susceptible patients or when given at higher doses cannot be ruled out. 8.5 Geriatric Use A total of 280 patients above 64 years of age with allergic rhinitis or chronic rhinosinusitis with nasal polyps (age range 64 to 86 years) have been treated with mometasone furoate nasal spray for up to 3 or 4 months, respectively. No observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients. 8.6 Hepatic Impairment Concentrations of mometasone furoate appear to increase with severity of hepatic impairment [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Risk Summary Mometasone is minimally absorbed systemically following nasal use, and maternal use is not expected to result in fetal exposure to the drug. Available data from observational studies of mometasone use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies with pregnant mice, rats, or rabbits (subcutaneous, subcutaneous/topical dermal/oral, and topical dermal/oral, respectively), mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data]. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at a dose less than the maximum recommended daily intranasal dose (MRDID) (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure less than the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 10 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at a dose approximately 6 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above).

organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at a dose approximately 30 times of the MRDID (on a mcg/m 2 basis with a maternal oral dose of 700 mcg/kg). At approximately 110 times the MRDID (on a mcg/m 2 basis with a maternal oral dose of 2,800 mcg/kg), most litters were aborted or resorbed. No effects were observed at a dose approximately 6 times the MRDID (on a mcg/m 2 basis with a maternal oral dose of 140 mcg/kg).

Risk Summary Mometasone is minimally absorbed systemically following nasal use, and maternal use is not expected to result in fetal exposure to the drug. Available data from observational studies of mometasone use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies with pregnant mice, rats, or rabbits (subcutaneous, subcutaneous/topical dermal/oral, and topical dermal/oral, respectively), mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data]. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at a dose less than the maximum recommended daily intranasal dose (MRDID) (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure less than the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 10 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at a dose approximately 6 times the MRDID (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings at a dose less than the MRDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at doses approximately 6 times the MRDID (on mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above).

8.2 Lactation Risk Summary There are no available data on the presence of mometasone furoate nasal spray in human milk, the effects on the breastfed child, or the effects on milk production. However, mometasone is minimally absorbed systemically by the mother following nasal use, and breastfeeding is not expected to result in exposure of the infant to mometasone. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mometasone furoate nasal spray and any potential adverse effects on the breastfed infant from mometasone furoate nasal spray or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of mometasone furoate nasal spray for prophylaxis of the nasal symptoms of seasonal allergic rhinitis in pediatric patients 12 years of age and older have been established [see Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.1 )]. Use of mometasone furoate nasal spray forthis indication is supported by evidence from controlled trials in adult and pediatric patients 12 years of age and older [see Clinical Studies ( 14.1 )]. The safety and effectiveness of mometasone furoate nasal spray for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients less than 18 years of age have not been established. Effectiveness was not demonstrated in one 4-month trial conducted to evaluate the safety and efficacy of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients 6 to 17 years of age. The primary objective of the study was to evaluate safety; efficacy parameters were collected as secondary endpoints. A total of 127 patients with chronic rhinosinusitis with nasal polyps were randomized to placebo or mometasone furoate nasal spray 100 mcg once or twice daily (patients 6 to 11 years of age) or 200 mcg once or twice daily (patients 12 to 17 years of age). The results of this trial did not support the efficacy of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients. The adverse reactions reported in this trial were similar to the adverse reactions reported in patients 18 years of age and older with chronic rhinosinusitis with nasal polyps. Effect on Growth Controlled clinical studies have shown nasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch up" growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving nasal corticosteroids, including mometasone furoate nasal spray, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of nasal corticosteroids, including mometasone furoate nasal spray, each patient should be titrated to his/her lowest effective dose. A clinical study to assess the effect of mometasone furoate nasal spray (100 mcg total daily dose) on growth velocity has been conducted in pediatric patients 3 to 9 years of age with allergic rhinitis. No statistically significant effect on growth velocity was observed for mometasone furoate nasal spray compared to placebo following one year of treatment. No evidence of clinically relevant HPA axis suppression was observed following a 30-minute cosyntropin infusion.

atients 3 to 9 years of age with allergic rhinitis. No statistically significant effect on growth velocity was observed for mometasone furoate nasal spray compared to placebo following one year of treatment. No evidence of clinically relevant HPA axis suppression was observed following a 30-minute cosyntropin infusion. The potential of mometasone furoate nasal spray to cause growth suppression in susceptible patients or when given at higher doses cannot be ruled out.

8.5 Geriatric Use A total of 280 patients above 64 years of age with allergic rhinitis or chronic rhinosinusitis with nasal polyps (age range 64 to 86 years) have been treated with mometasone furoate nasal spray for up to 3 or 4 months, respectively. No observed differences in safety and/or effectiveness in geriatric patients compared to younger adult patients.

10 OVERDOSAGE There are no data available on the effects of acute or chronic overdosage with mometasone furoate nasal spray. Because of low systemic bioavailability, and an absence of acute drug-related systemic findings in clinical studies, overdose is unlikely to require any therapy other than observation. Chronic overdosage with any corticosteroid may result in signs or symptoms of hypercorticism. [ see Warnings and Precautions ( 5.5 ) ].

11 DESCRIPTION Mometasone furoate, the active component of mometasone furoate nasal spray, 50 mcg, is an anti-inflammatory corticosteroid having the chemical name, 9,21-Dichloro-11ß,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione17-(2 furoate), and the following chemical structure: Mometasone furoate is a white to off-white powder, with an molecular formula of C 27 H 30 Cl 2 O 6 , and a molecular weight of 521.43. It is practically insoluble in water, slightly soluble in methanol, ethanol, and isopropanol; soluble in acetone, chloroform, and methylene chloride; and freely soluble in tetrahydrofuran, acetone and dichloromethane. Its partition coefficient between octanol and water is greater than 5,000. Mometasone furoate nasal spray 50 mcg is a metered-dose, manual pump spray unit containing an aqueous suspension of 0.05% w/w mometasone furoate in an aqueous medium containing benzalkonium chloride, citric acid, glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, polysorbate 80, purified water, and sodium citrate. The pH is between 4.3 and 4.9. structure

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mometasone furoate nasal spray is a corticosteroid demonstrating potent anti-inflammatory properties. The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. In two clinical studies utilizing nasal antigen challenge, mometasone furoate nasal spray decreased some markers of the early- and late-phase allergic response. These observations included decreases (vs. placebo) in histamine and eosinophil cationic protein levels, and reductions (vs. baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins. The clinical significance of these findings is not known. The effect of mometasone furoate nasal spray on nasal mucosa following 12 months of treatment was examined in 46 patients with allergic rhinitis. There was no evidence of atrophy and there was a marked reduction in intraepithelial eosinophilia and inflammatory cell infiltration (e.g., eosinophils, lymphocytes, monocytes, neutrophils, and plasma cells). 12.2 Pharmacodynamics Adrenal Function in Adults: Four clinical pharmacology studies have been conducted in humans to assess the effect of mometasone furoate nasal spray at various doses on adrenal function. In one study, daily doses of 200 and 400 mcg of mometasone furoate nasal spray and 10 mg of prednisone were compared to placebo in 64 patients (22 to 44 years of age) with allergic rhinitis. Adrenal function before and after 36 consecutive days of treatment was assessed by measuring plasma cortisol levels following a 6-hour Cortrosyn (ACTH) infusion and by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both the 200- and 400-mcg dose, was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. A statistically significant decrease in the mean plasma cortisol levels post-Cortrosyn infusion and 24-hour urinary free cortisol levels was detected in the prednisone treatment group compared to placebo. A second study assessed adrenal response to mometasone furoate nasal spray (400 and 1,600 mcg/day), prednisone (10 mg/day), and placebo, administered for 29 days in 48 male volunteers (21 to 40 years of age). The 24-hour plasma cortisol area under the curve (AUC 0–24 ), during and after an 8-hour Cortrosyn infusion and 24-hour urinary free cortisol levels were determined at baseline and after 29 days of treatment. No statistically significant differences in adrenal function were observed with mometasone furoate nasal spray compared to placebo. A third study evaluated single, rising doses of mometasone furoate nasal spray (1,000, 2,000, and 4,000 mcg/day), orally administered mometasone furoate (2,000, 4,000, and 8,000 mcg/day), orally administered dexamethasone (200, 400, and 800 mcg/day), and placebo (administered at the end of each series of doses) in 24 male volunteers (22 to 39 years of age). Dose administrations were separated by at least 72 hours.

4,000 mcg/day), orally administered mometasone furoate (2,000, 4,000, and 8,000 mcg/day), orally administered dexamethasone (200, 400, and 800 mcg/day), and placebo (administered at the end of each series of doses) in 24 male volunteers (22 to 39 years of age). Dose administrations were separated by at least 72 hours. Determination of serial plasma cortisol levels at 8 AM and for the 24-hour period following each treatment were used to calculate the plasma cortisol area under the curve (AUC 0–24 ). In addition, 24-hour urinary free cortisol levels were collected prior to initial treatment administration and during the period immediately following each dose. No statistically significant decreases in the plasma cortisol AUC, 8 AM cortisol levels, or 24-hour urinary free cortisol levels were observed in volunteers treated with either mometasone furoate nasal spray or oral mometasone, as compared with placebo treatment. Conversely, nearly all volunteers treated with the three doses of dexamethasone demonstrated abnormal 8 AM cortisol levels (defined as a cortisol level <10 mcg/dL), reduced 24-hour plasma AUC values, and decreased 24-hour urinary free cortisol levels, as compared to placebo treatment. In a fourth study, adrenal function was assessed in 213 patients (18 to 81 years of age) with chronic rhinosinusitis with nasal polyps before and after 4 months of treatment with either mometasone furoate nasal spray (200 mcg once or twice daily) or placebo by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both doses (200 and 400 mcg/day), was not associated with statistically significant decreases in the 24-hour urinary free cortisol levels compared to placebo. Three clinical pharmacology studies have been conducted in pediatric patients to assess the effect of mometasone furoate nasal spray on the adrenal function at daily doses of 50, 100, and 200 mcg vs. placebo. In one study, adrenal function before and after 7 consecutive days of treatment was assessed in 48 pediatric patients with allergic rhinitis (ages 6 to 11 years) by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray, at all three doses, was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. In the second study, adrenal function before and after 14 consecutive days of treatment was assessed in 48 pediatric patients (ages 3 to 5 years) with allergic rhinitis by measuring plasma cortisol levels following a 30-minute Cortrosyn infusion. Mometasone furoate nasal spray, 50 mcg, at all three doses (50, 100, and 200 mcg/day), was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion compared to placebo. All patients had a normal response to Cortrosyn. In the third study, adrenal function before and after up to 42 consecutive days of once-daily treatment was assessed in 52 patients with allergic rhinitis (ages 2 to 5 years), 28 of whom received mometasone furoate nasal spray, 50 mcg per nostril (total daily dose 100 mcg), by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. 12.3 Pharmacokinetics Absorption : Mometasone furoate monohydrate administered as a nasal spray suspension has very low bioavailability (<1%) in plasma using a sensitive assay with a lower quantitation limit (LOQ) of 0.25 pcg/mL.

ally significant decrease in the 24-hour urinary free cortisol levels compared to placebo. 12.3 Pharmacokinetics Absorption : Mometasone furoate monohydrate administered as a nasal spray suspension has very low bioavailability (<1%) in plasma using a sensitive assay with a lower quantitation limit (LOQ) of 0.25 pcg/mL. Distribution : The in vitro protein binding for mometasone furoate was reported to be 98% to 99% in concentration range of 5 to 500 ng/mL. Elimination: Following intravenous administration, the effective plasma elimination half-life of mometasone furoate is 5.8 hours. Any absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine. Metabolism: Studies have shown that any portion of a mometasone furoate dose which is swallowed and absorbed undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. Upon in vitro incubation, one of the minor metabolites formed is 6ß-hydroxymometasone furoate. In human liver microsomes, the formation of the metabolite is regulated by cytochrome P-450 3A4 (CYP3A4). Specific Populations: Patients with Hepatic Impairment: Administration of a single inhaled dose of 400 mcg mometasone furoate to subjects with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable peak plasma concentrations of mometasone furoate (ranging from 50 to 105 pcg/mL). The observed peak plasma concentrations appear to increase with severity of hepatic impairment, however, the numbers of detectable levels were few. Patients with Renal Impairment: The effects of renal impairment on mometasone furoate pharmacokinetics have not been adequately investigated. Pediatric Patients: Mometasone furoate pharmacokinetics have not been investigated in the pediatric population [ see Use in Specific Populations (8.4) ]. Male and Female Patients: The effects of gender on mometasone furoate pharmacokinetics have not been adequately investigated. Racial or Ethnic Groups: The effects of race on mometasone furoate pharmacokinetics have not been adequately investigated. Drug Interaction Studies: Inhibitors of Cytochrome P450 3A4: In a drug interaction study, an inhaled dose of mometasone furoate 400 mcg was given to 24 healthy subjects twice daily for 9 days and ketoconazole 200 mg (as well as placebo) were given twice daily concomitantly on Days 4 to 9. Mometasone furoate plasma concentrations were <150 pcg/mL on Day 3 prior to coadministration of ketoconazole or placebo. Following concomitant administration of ketoconazole, 4 out of 12 subjects in the ketoconazole treatment group (n=12) had peak plasma concentrations of mometasone furoate >200 pcg/mL on Day 9 (211 to 324 pcg/mL).

12.1 Mechanism of Action Mometasone furoate nasal spray is a corticosteroid demonstrating potent anti-inflammatory properties. The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. In two clinical studies utilizing nasal antigen challenge, mometasone furoate nasal spray decreased some markers of the early- and late-phase allergic response. These observations included decreases (vs. placebo) in histamine and eosinophil cationic protein levels, and reductions (vs. baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins. The clinical significance of these findings is not known. The effect of mometasone furoate nasal spray on nasal mucosa following 12 months of treatment was examined in 46 patients with allergic rhinitis. There was no evidence of atrophy and there was a marked reduction in intraepithelial eosinophilia and inflammatory cell infiltration (e.g., eosinophils, lymphocytes, monocytes, neutrophils, and plasma cells).

12.2 Pharmacodynamics Adrenal Function in Adults: Four clinical pharmacology studies have been conducted in humans to assess the effect of mometasone furoate nasal spray at various doses on adrenal function. In one study, daily doses of 200 and 400 mcg of mometasone furoate nasal spray and 10 mg of prednisone were compared to placebo in 64 patients (22 to 44 years of age) with allergic rhinitis. Adrenal function before and after 36 consecutive days of treatment was assessed by measuring plasma cortisol levels following a 6-hour Cortrosyn (ACTH) infusion and by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both the 200- and 400-mcg dose, was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. A statistically significant decrease in the mean plasma cortisol levels post-Cortrosyn infusion and 24-hour urinary free cortisol levels was detected in the prednisone treatment group compared to placebo. A second study assessed adrenal response to mometasone furoate nasal spray (400 and 1,600 mcg/day), prednisone (10 mg/day), and placebo, administered for 29 days in 48 male volunteers (21 to 40 years of age). The 24-hour plasma cortisol area under the curve (AUC 0–24 ), during and after an 8-hour Cortrosyn infusion and 24-hour urinary free cortisol levels were determined at baseline and after 29 days of treatment. No statistically significant differences in adrenal function were observed with mometasone furoate nasal spray compared to placebo. A third study evaluated single, rising doses of mometasone furoate nasal spray (1,000, 2,000, and 4,000 mcg/day), orally administered mometasone furoate (2,000, 4,000, and 8,000 mcg/day), orally administered dexamethasone (200, 400, and 800 mcg/day), and placebo (administered at the end of each series of doses) in 24 male volunteers (22 to 39 years of age). Dose administrations were separated by at least 72 hours. Determination of serial plasma cortisol levels at 8 AM and for the 24-hour period following each treatment were used to calculate the plasma cortisol area under the curve (AUC 0–24 ). In addition, 24-hour urinary free cortisol levels were collected prior to initial treatment administration and during the period immediately following each dose. No statistically significant decreases in the plasma cortisol AUC, 8 AM cortisol levels, or 24-hour urinary free cortisol levels were observed in volunteers treated with either mometasone furoate nasal spray or oral mometasone, as compared with placebo treatment. Conversely, nearly all volunteers treated with the three doses of dexamethasone demonstrated abnormal 8 AM cortisol levels (defined as a cortisol level <10 mcg/dL), reduced 24-hour plasma AUC values, and decreased 24-hour urinary free cortisol levels, as compared to placebo treatment. In a fourth study, adrenal function was assessed in 213 patients (18 to 81 years of age) with chronic rhinosinusitis with nasal polyps before and after 4 months of treatment with either mometasone furoate nasal spray (200 mcg once or twice daily) or placebo by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both doses (200 and 400 mcg/day), was not associated with statistically significant decreases in the 24-hour urinary free cortisol levels compared to placebo.

ther mometasone furoate nasal spray (200 mcg once or twice daily) or placebo by measuring 24-hour urinary free cortisol levels. Mometasone furoate nasal spray at both doses (200 and 400 mcg/day), was not associated with statistically significant decreases in the 24-hour urinary free cortisol levels compared to placebo. Three clinical pharmacology studies have been conducted in pediatric patients to assess the effect of mometasone furoate nasal spray on the adrenal function at daily doses of 50, 100, and 200 mcg vs. placebo. In one study, adrenal function before and after 7 consecutive days of treatment was assessed in 48 pediatric patients with allergic rhinitis (ages 6 to 11 years) by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray, at all three doses, was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo. In the second study, adrenal function before and after 14 consecutive days of treatment was assessed in 48 pediatric patients (ages 3 to 5 years) with allergic rhinitis by measuring plasma cortisol levels following a 30-minute Cortrosyn infusion. Mometasone furoate nasal spray, 50 mcg, at all three doses (50, 100, and 200 mcg/day), was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion compared to placebo. All patients had a normal response to Cortrosyn. In the third study, adrenal function before and after up to 42 consecutive days of once-daily treatment was assessed in 52 patients with allergic rhinitis (ages 2 to 5 years), 28 of whom received mometasone furoate nasal spray, 50 mcg per nostril (total daily dose 100 mcg), by measuring morning plasma cortisol and 24-hour urinary free cortisol levels. Mometasone furoate nasal spray was not associated with a statistically significant decrease in mean plasma cortisol levels or a statistically significant decrease in the 24-hour urinary free cortisol levels compared to placebo.

12.3 Pharmacokinetics Absorption : Mometasone furoate monohydrate administered as a nasal spray suspension has very low bioavailability (<1%) in plasma using a sensitive assay with a lower quantitation limit (LOQ) of 0.25 pcg/mL. Distribution : The in vitro protein binding for mometasone furoate was reported to be 98% to 99% in concentration range of 5 to 500 ng/mL. Elimination: Following intravenous administration, the effective plasma elimination half-life of mometasone furoate is 5.8 hours. Any absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine. Metabolism: Studies have shown that any portion of a mometasone furoate dose which is swallowed and absorbed undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. Upon in vitro incubation, one of the minor metabolites formed is 6ß-hydroxymometasone furoate. In human liver microsomes, the formation of the metabolite is regulated by cytochrome P-450 3A4 (CYP3A4). Specific Populations: Patients with Hepatic Impairment: Administration of a single inhaled dose of 400 mcg mometasone furoate to subjects with mild (n=4), moderate (n=4), and severe (n=4) hepatic impairment resulted in only 1 or 2 subjects in each group having detectable peak plasma concentrations of mometasone furoate (ranging from 50 to 105 pcg/mL). The observed peak plasma concentrations appear to increase with severity of hepatic impairment, however, the numbers of detectable levels were few. Patients with Renal Impairment: The effects of renal impairment on mometasone furoate pharmacokinetics have not been adequately investigated. Pediatric Patients: Mometasone furoate pharmacokinetics have not been investigated in the pediatric population [ see Use in Specific Populations (8.4) ]. Male and Female Patients: The effects of gender on mometasone furoate pharmacokinetics have not been adequately investigated. Racial or Ethnic Groups: The effects of race on mometasone furoate pharmacokinetics have not been adequately investigated. Drug Interaction Studies: Inhibitors of Cytochrome P450 3A4: In a drug interaction study, an inhaled dose of mometasone furoate 400 mcg was given to 24 healthy subjects twice daily for 9 days and ketoconazole 200 mg (as well as placebo) were given twice daily concomitantly on Days 4 to 9. Mometasone furoate plasma concentrations were <150 pcg/mL on Day 3 prior to coadministration of ketoconazole or placebo. Following concomitant administration of ketoconazole, 4 out of 12 subjects in the ketoconazole treatment group (n=12) had peak plasma concentrations of mometasone furoate >200 pcg/mL on Day 9 (211 to 324 pcg/mL).

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 1 and 2 times the maximum recommended daily nasal dose [MRDID] in adults [400 mcg] and children [100 mcg], respectively, on a mcg/m 2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 2 times the MRDID in adults and children, respectively, on a mcg/m 2 basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary-cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse-lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay and a rat bone marrow chromosomal aberration assay or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (less than the MRDID in adults on a mcg/m 2 basis). 13.2 Animal Toxicology and/or Pharmacology Reproduction Toxicology Studies In mice, mometasone furoate caused cleft palate at subcutaneous doses of 60 mcg/kg and above (less than the MRDID in adults on a mcg/m 2 basis). Fetal survival was reduced at 180 mcg/kg (approximately 2 times the MRDID in adults on a mcg/m 2 basis). No toxicity was observed at 20 mcg/kg (less than the MRDID in adults on a mcg/m 2 basis). In rats, mometasone furoate produced umbilical hernia at topical dermal doses of 600 mcg/kg and above (approximately 10 times the MRDID in adults on a mcg/m 2 basis). A dose of 300 mcg/kg (approximately 6 times the MRDID in adults on a mcg/m 2 basis) produced delays in ossification, but no malformations. In rabbits, mometasone furoate caused multiple malformations (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at topical dermal doses of 150 mcg/kg and above (approximately 6 times the MRDID in adults on a mcg/m 2 basis). In an oral study, mometasone furoate increased resorptions and caused cleft palate and/or head malformations (hydrocephaly or domed head) at 700 mcg/kg (approximately 30 times the MRDID in adults on a mcg/m 2 basis). At 2,800 mcg/kg (approximately 110 times the MRDID in adults on a mcg/m 2 basis), most litters were aborted or resorbed. No toxicity was observed at 140 mcg/kg (approximately 6 times the MRDID in adults 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 (less than the MRDID in adults on a mcg/m 2 basis) 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 (less than the MRDID in adults on a mcg/m 2 basis).

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 1 and 2 times the maximum recommended daily nasal dose [MRDID] in adults [400 mcg] and children [100 mcg], respectively, on a mcg/m 2 basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 2 times the MRDID in adults and children, respectively, on a mcg/m 2 basis). Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary-cell assay, but did not increase chromosomal aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse-lymphoma assay, and was not clastogenic in an in vivo mouse micronucleus assay and a rat bone marrow chromosomal aberration assay or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (less than the MRDID in adults on a mcg/m 2 basis).

13.2 Animal Toxicology and/or Pharmacology Reproduction Toxicology Studies In mice, mometasone furoate caused cleft palate at subcutaneous doses of 60 mcg/kg and above (less than the MRDID in adults on a mcg/m 2 basis). Fetal survival was reduced at 180 mcg/kg (approximately 2 times the MRDID in adults on a mcg/m 2 basis). No toxicity was observed at 20 mcg/kg (less than the MRDID in adults on a mcg/m 2 basis). In rats, mometasone furoate produced umbilical hernia at topical dermal doses of 600 mcg/kg and above (approximately 10 times the MRDID in adults on a mcg/m 2 basis). A dose of 300 mcg/kg (approximately 6 times the MRDID in adults on a mcg/m 2 basis) produced delays in ossification, but no malformations. In rabbits, mometasone furoate caused multiple malformations (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at topical dermal doses of 150 mcg/kg and above (approximately 6 times the MRDID in adults on a mcg/m 2 basis). In an oral study, mometasone furoate increased resorptions and caused cleft palate and/or head malformations (hydrocephaly or domed head) at 700 mcg/kg (approximately 30 times the MRDID in adults on a mcg/m 2 basis). At 2,800 mcg/kg (approximately 110 times the MRDID in adults on a mcg/m 2 basis), most litters were aborted or resorbed. No toxicity was observed at 140 mcg/kg (approximately 6 times the MRDID in adults 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 (less than the MRDID in adults on a mcg/m 2 basis) 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 (less than the MRDID in adults on a mcg/m 2 basis).

14 CLINICAL STUDIES 14.1 Prophylaxis of Seasonal Allergic Rhinitis in Adult and Pediatric Patients 12 Years of Age and Older The efficacy and safety of mometasone furoate nasal spray in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis have been evaluated in 18 controlled trials, and one uncontrolled clinical trial, in approximately 3,000 adults (ages 17 to 85 years) and pediatric patients (ages 12 to 16 years). Of the total number of patients, there were 1,757 males and 1,453 females, including a total of 283 adolescents (182 boys and 101 girls) with seasonal allergic or perennial allergic rhinitis. Patients were treated with mometasone furoate nasal spray at doses ranging from 50 to 800 mcg/day. The majority of patients were treated with 200 mcg/day. The allergic rhinitis trials evaluated the total nasal symptom scores that included stuffiness, rhinorrhea, itching, and sneezing. Patients treated with mometasone furoate nasal spray 200 mcg/day had a statistically significant decrease in total nasal symptom scores compared to placebo-treated patients. No additional benefit was observed for mometasone furoate doses greater than 200 mcg/day. A total of 350 patients have been treated with mometasone furoate nasal spray for 1 year or longer. Prophylaxis of seasonal allergic rhinitis for patients 12 years of age and older with mometasone furoate nasal spray given at a dose of 200 mcg/day, was evaluated in two clinical studies in 284 patients. These studies were designed such that patients received 4 weeks of prophylaxis with mometasone furoate nasal spray prior to the anticipated onset of the pollen season; however, some patients received only 2 to 3 weeks of prophylaxis. Patients receiving 2 to 4 weeks of prophylaxis with mometasone furoate nasal spray demonstrated a statistically significantly smaller mean increase in total nasal symptom scores with onset of the pollen season as compared to placebo patients. 14.2 Chronic Rhinosinusitis with Nasal Polyps in Adults 18 Years of Age and Older Two studies were performed to evaluate the efficacy and safety of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis with nasal polyps. These studies involved 664 patients with chronic rhinosinusitis with nasal polyps, 441 of whom received mometasone furoate nasal spray. These studies were randomized, double-blind, placebo-controlled, parallel-group, multicenter studies in patients 18 to 86 years of age with bilateral nasal polyps. Patients were randomized to receive mometasone furoate nasal spray 200 mcg once daily, 200 mcg twice daily or placebo for a period of 4 months. The co-primary efficacy endpoints were 1) change from baseline in nasal congestion/obstruction averaged over the first month of treatment; and 2) change from baseline to last assessment in bilateral polyp grade during the entire 4 months of treatment as assessed by endoscopy. Efficacy was demonstrated in both studies at a dose of 200 mcg twice daily and in one study at a dose of 200 mcg once a day (see Table 2 below). Table 2: Effect of Mometasone Furoate Nasal Spray in Two Randomized, Placebo-Controlled Trials in Patients with Chronic Rhinosinusitis with Nasal Polyps Mometasone Furoate Nasal Spray 200 mcg qd Mometasone Furoate Nasal Spray 200 mcg bid Placebo P - value for Mometasone Furoate Nasal Spray 200 mcg qd vs. placebo P - value for Mometasone Furoate Nasal Spray 200 mcg bid vs.

wo Randomized, Placebo-Controlled Trials in Patients with Chronic Rhinosinusitis with Nasal Polyps Mometasone Furoate Nasal Spray 200 mcg qd Mometasone Furoate Nasal Spray 200 mcg bid Placebo P - value for Mometasone Furoate Nasal Spray 200 mcg qd vs. placebo P - value for Mometasone Furoate Nasal Spray 200 mcg bid vs. placebo Study 1 N=115 N=122 N=117 Baseline bilateral polyp grade * 4.21 4.27 4.25 Mean change from baseline in bilateral polyps grade -1.15 -0.96 -0.50 <0.001 0.01 Baseline nasal congestion † 2.29 2.35 2.28 Mean change from baseline in nasal congestion -0.47 -0.61 -0.24 0.001 <0.001 Study 2 N=102 N=102 N=106 Baseline bilateral polyp grade* 4.00 4.10 4.17 Mean change from baseline in bilateral polyps grade -0.78 -0.96 -0.62 0.33 0.04 Baseline nasal congestion † 2.23 2.20 2.18 Mean change from baseline in nasal congestion -0.42 -0.66 -0.23 0.01 <0.001 * polyps in each nasal fossa were graded by the investigator based on endoscopic visualization, using a scale of 0-3 where 0=no polyps; 1=polyps in the middle meatus, not reaching below the inferior border of the middle turbinate; 2=polyps reaching below the inferior border of the middle turbinate but not the inferior border of the inferior turbinate; 3=polyps reaching to or below the border of the inferior turbinate, or polyps medial to the middle turbinate (score reflects sum of left and right nasal fossa grades). † nasal congestion/obstruction was scored daily by the patient using a 0-3 categorical scale where 0=no symptoms, 1=mild symptoms, 2=moderate symptoms and 3=severe symptoms. There were no clinically relevant differences in the effectiveness of mometasone furoate nasal spray in the studies evaluating treatment of chronic rhinosinusitis with nasal polyps across subgroups of patients defined by gender, age, or race.

<table rules="all"><tbody align="center"><tr><td> </td><td align="center"><content styleCode="bold">Mometasone Furoate Nasal Spray</content><content styleCode="bold"> 200 mcg qd</content></td><td align="center"><content styleCode="bold">Mometasone Furoate Nasal Spray</content> <content styleCode="bold">200 mcg bid</content></td><td align="center"><content styleCode="bold">Placebo</content></td><td align="center"><content styleCode="bold italics">P</content><content styleCode="bold">-</content><content styleCode="bold">value for Mometasone Furoate Nasal Spray</content><content styleCode="bold"> 200 mcg qd vs. placebo</content></td><td align="center"><content styleCode="bold italics">P</content><content styleCode="bold">-</content><content styleCode="bold">value for Mometasone Furoate Nasal Spray 200 mcg bid vs. placebo</content></td></tr><tr><td align="left"><content styleCode="bold">Study 1</content></td><td> N=115 </td><td> N=122 </td><td> N=117 </td><td> </td><td> </td></tr><tr><td align="left"> Baseline bilateral polyp grade^*</td><td> 4.21 </td><td> 4.27 </td><td> 4.25 </td><td> </td><td> </td></tr><tr><td align="left"> Mean change from baseline in bilateral polyps grade </td><td> -1.15 </td><td> -0.96 </td><td> -0.50 </td><td> &lt;0.001 </td><td> 0.01 </td></tr><tr><td align="left"> Baseline nasal congestion^&#x2020;</td><td> 2.29 </td><td> 2.35 </td><td> 2.28 </td><td> </td><td> </td></tr><tr><td align="left"> Mean change from baseline in nasal congestion </td><td> -0.47 </td><td> -0.61 </td><td> -0.24 </td><td> 0.001 </td><td> &lt;0.001 </td></tr><tr><td align="left"><content styleCode="bold">Study </content><content styleCode="bold">2</content></td><td> N=102 </td><td> N=102 </td><td> N=106 </td><td> </td><td> </td></tr><tr><td align="left"> Baseline bilateral polyp grade* </td><td> 4.00 </td><td> 4.10 </td><td> 4.17 </td><td> </td><td> </td></tr><tr><td align="left"> Mean change from baseline in bilateral polyps grade </td><td> -0.78 </td><td> -0.96 </td><td> -0.62 </td><td> 0.33 </td><td> 0.04 </td></tr><tr><td align="left"> Baseline nasal congestion^&#x2020;</td><td> 2.23 </td><td> 2.20 </td><td> 2.18 </td><td> </td><td> </td></tr><tr><td align="left"> Mean change from baseline in nasal congestion </td><td> -0.42 </td><td> -0.66 </td><td> -0.23 </td><td> 0.01 </td><td> &lt;0.001 </td></tr></tbody></table>

16 HOW SUPPLIED/STORAGE AND HANDLING Mometasone Furoate Nasal Spray: 50 mcg mometasone furoate per spray is supplied in a white, high-density, polyethylene bottle fitted with a white metered-dose, manual spray pump, and translucent cap contains 17 g of product formulation (NDC 60505-0830-1) 120 sprays, each delivering 50 mcg of mometasone furoate per actuation Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light. When mometasone furoate nasal spray is removed from its cardboard container, prolonged exposure of the product to direct light should be avoided. Brief exposure to light, as with normal use, is acceptable. SHAKE WELL BEFORE EACH USE.

Mometasone Furoate Nasal Spray: 50 mcg mometasone furoate per spray is supplied in a white, high-density, polyethylene bottle fitted with a white metered-dose, manual spray pump, and translucent cap contains 17 g of product formulation (NDC 60505-0830-1) 120 sprays, each delivering 50 mcg of mometasone furoate per actuation Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light. When mometasone furoate nasal spray is removed from its cardboard container, prolonged exposure of the product to direct light should be avoided. Brief exposure to light, as with normal use, is acceptable. SHAKE WELL BEFORE EACH USE.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Local Nasal Adverse Reactions Patients should be informed that treatment with mometasone furoate nasal spray may be associated with adverse reactions which include epistaxis (nose bleed) and nasal septum perforation. Candida infection may also occur. Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septum ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred [ see Warnings and Precautions (5.1) ]. Patients should be cautioned not to spray mometasone furoate nasal spray directly onto the nasal septum. Glaucoma and Cataracts Advise patients that long-term use of nasal and inhaled corticosteroids may increase the risk of some eye problems (glaucoma or cataracts); regular eye examinations should be considered. Patients should be cautioned not to spray mometasone furoate nasal spray into the eyes [ see Warnings and Precautions ( 5.2 ) ]. Immunosuppression and Risk of Infections Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles, and patients should also be advised that if they are exposed, medical advice should be sought without delay [ see Warnings and Precautions (5.4) ]. Use Regularly for Best Effect Patients should use mometasone furoate nasal spray on a regular basis for optimal effect. Improvement in nasal symptoms of allergic rhinitis has been shown to occur within 1 to 2 days after initiation of dosing. Maximum benefit is usually achieved within 1 to 2 weeks after initiation of dosing. Patients should not increase the prescribed dosage but should contact their physician if symptoms do not improve, or if the condition worsens. Administration to young children should be aided by an adult. If a patient missed a dose, the patient should be advised to administer the dose as soon as they remember. The patient should not use more than the recommended dose for the day.

<table border="null" frame="void" rules="groups"><tbody align="left"><tr><th colspan="1" rowspan="1">Manufactured by:</th><th colspan="50" rowspan="1"/><th>Manufactured for:</th></tr><tr><th colspan="1">Apotex Inc.</th><th colspan="50"/><th colspan="1">Apotex Corp.</th></tr><tr><th colspan="1">Toronto, Ontario</th><th colspan="50"/><th colspan="1">Weston, FL</th></tr><tr><th colspan="1">M9L 1T9</th><th colspan="50"/><th colspan="1">33326</th></tr></tbody></table>

PATIENT INFORMATION Mometasone Furoate (moe met' a sone fure' oh ate) Nasal Spray, 50 mcg For Nasal Use Only Read the Patient Information that comes with mometasone furoate nasal spray before you start using it and each time you get a refill. There may be new information. This Patient Information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about mometasone furoate nasal spray, ask your healthcare provider. What is mometasone furoate nasal spray? Mometasone furoate nasal spray is a man-made (synthetic) corticosteroid medicine that is used to: prevent nasal symptoms of seasonal allergic rhinitis in people 12 years of age and older. treat chronic rhinosinusitis with nasal polyps in people 18 years and older. It is not known if mometasone furoate nasal spray is safe and effective in children under: 12 years of age to prevent nasal symptoms of seasonal allergic rhinitis. 18 years of age to treat chronic rhinosinusitis with nasal polyps. Who should not use mometasone furoate nasal spray? Do not use mometasone furoate nasal spray if you are allergic to mometasone furoate or any of the ingredients in mometasone furoate nasal spray. See the end of this leaflet for a complete list of ingredients in mometasone furoate nasal spray. What should I tell my healthcare provider before and during treatment with mometasone furoate nasal spray? Before you take mometasone furoate nasal spray, tell your healthcare provider about all of your medical conditions, including if you: have had recent nasal sores, nasal surgery, or nasal injury. have eye or vision problems, such as cataracts, glaucoma (increased pressure in your eye), and blurred vision, or other changes in your vision. have tuberculosis or any untreated fungal, bacterial, viral infections, or eye infections caused by herpes. have been near someone who has chickenpox or measles. are not feeling well or have any other symptoms that you do not understand. are pregnant or planning to become pregnant. It is not known if mometasone furoate nasal spray will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. are breastfeeding or planning to breastfeed. It is not known whether mometasone furoate passes into your breast milk. Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take: certain medicines for HIV (such as ritonavir, atazanavir, indinavir, nelfinavir, and saquinavir) cobicistat-containing products certain antifungals (such as ketoconazole and itraconazole) certain antibiotics (such as clarithromycin and telithromycin) certain antidepressants (such as nefazodone) If you take these medicines with mometasone furoate nasal spray, your healthcare provider should monitor you for side effects. Mometasone furoate nasal spray may affect the way other medicines work, and other medicines may affect how mometasone furoate nasal spray works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use mometasone furoate nasal spray? Use mometasone furoate nasal spray exactly as prescribed by your healthcare provider. This medicine is for use in the nose only. Do not spray it into your mouth or eyes.

ake. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use mometasone furoate nasal spray? Use mometasone furoate nasal spray exactly as prescribed by your healthcare provider. This medicine is for use in the nose only. Do not spray it into your mouth or eyes. An adult should supervise a child using this medicine. For best results, you should keep using mometasone furoate nasal spray regularly each day without missing a dose. If you do miss a dose of mometasone furoate nasal spray, take it as soon as you remember. However, do not take more than the daily dose prescribed by your healthcare provider. Do not use mometasone furoate nasal spray more often than prescribed. Ask your healthcare provider if you have any questions. For detailed instructions on how to use mometasone furoate nasal spray, see the " Patient Instructions for Use " at the end of this leaflet. See your healthcare provider regularly to check your symptoms while taking mometasone furoate nasal spray and to check for side effects. What should I avoid while taking mometasone furoate nasal spray? If you are taking other corticosteroid medicines for allergy, by mouth or injection, your healthcare provider may advise you to stop taking them after you begin using mometasone furoate nasal spray. What are the possible side effects of mometasone furoate nasal spray? Mometasone furoate nasal spray may cause serious side effects, including: thrush (candida), a fungal infection in your nose and throat. Tell your healthcare provider if you have any redness or white colored patches in your nose or throat. hole in the cartilage of the nose (nasal septal perforation). A whistling sound when you breathe may be a symptom of nasal septum perforation. slow wound healing. Do not use mometasone furoate nasal spray until your nose has healed if you have a sore in your nose, if you have surgery on your nose, or if your nose has been injured. eye problems, including glaucoma, cataracts, and blurred vision. You should have regular eye exams. allergic reactions . Allergic reactions including wheezing may happen after using mometasone furoate nasal spray. If w heezing happens stop using mometasone furoate nasal spray. Tell your healthcare provider or get medical help right away . immune system problems that may increase your risk of infections. You are more likely to get infections if you take medicines that weaken your immune system. Avoid contact with people who have contagious diseases such as chicken pox or measles while using mometasone furoate nasal spray. Symptoms of infection may include: fever, pain, aches, chills, feeling tired, nausea, and vomiting. Tell your healthcare provider about any signs of infection while you are using mometasone furoate nasal spray. adrenal insufficiency. Adrenal insufficiency is a condition in which the adrenal glands do not make enough steroid hormones. Symptoms of adrenal insufficiency can include: tiredness, weakness, nausea and vomiting, and low blood pressure. slowed growth in children. Your child’s growth should be checked regularly while using mometasone furoate nasal spray. The most common side effects of mometasone furoate nasal spray include: headache viral infection sore throat nosebleeds cough These are not all the possible side effects of mometasone furoate nasal spray. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store mometasone furoate nasal spray? Store mometasone furoate nasal spray at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Protect from light. Avoid prolonged exposure of mometasone furoate nasal spray container to direct light. Shake well before each use.

ts to FDA at 1-800-FDA-1088. How should I store mometasone furoate nasal spray? Store mometasone furoate nasal spray at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Protect from light. Avoid prolonged exposure of mometasone furoate nasal spray container to direct light. Shake well before each use. Keep mometasone furoate nasal spray and all medicines out of the reach of children. General information about the safe and effective use of mometasone furoate nasal spray Medicines are sometimes prescribed for conditions that are not listed in a Patient Information leaflet. Do not use mometasone furoate nasal spray for a condition for which it was not prescribed. Do not give mometasone furoate nasal spray to other people even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about mometasone furoate nasal spray that is written for health professionals. What are the ingredients in mometasone furoate nasal spray? Active ingredients: mometasone furoate Inactive ingredients: benzalkonium chloride, citric acid, glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, polysorbate 80, purified water, and sodium citrate. For more information, go to www.apotex.com/products or call 1-800-706-5575. This Patient Information has been approved by the U.S. Food and Drug Administration APOTEX INC. MOMETASONE FUROATE NASAL SPRAY 50 mcg Manufactured by: Manufactured for: Apotex Inc. Toronto, Ontario M9L 1T9 Apotex Corp. Weston, FL 33326 Patient Instructions for Use Mometasone Furoate (moe met' a sone fure' oh ate) Nasal Spray, 50 mcg For use in your nose only. Read the Patient Instructions for Use carefully before you start to use your mometasone furoate nasal spray. If you have any questions, ask your healthcare provider. Shake the bottle well before each use. 1. Remove the plastic cap ( See Figure 1). 2. Before you use mometasone furoate nasal spray for the first time, prime the pump by pressing downward on the shoulders of the white nasal applicator using your index finger and middle finger while holding the base of the bottle with your thumb ( See Figure 2). Do Not pierce the nasal applicator. Press down and release the pump 10 times or until a fine spray appears. Do Not spray into eyes. The pump is now ready to use. The pump may be stored unused for up to 1 week without repriming. If unused for more than 1 week, reprime by spraying 2 times or until a fine spray appears. 3. Gently blow your nose to clear the nostrils. Close 1 nostril. Tilt your head forward slightly, keep the bottle upright, carefully insert the nasal applicator into the other nostril ( See Figure 3). Do Not spray directly onto the nasal septum (the wall between the two nostrils). 4. For each spray, hold the spray bottle upright and press firmly downward 1 time on the shoulders of the white nasal applicator using your index and middle fingers while supporting the base of the bottle with your thumb. Breathe gently inward through the nostril ( See Figure 4). Note: It is important to keep the Mometasone Furoate Nasal Spray unit in an upright orientation (as seen in Figure 4). Failure to do so may result in an incomplete or non-existent spray. 5. Then breathe out through the mouth. 6. Repeat in the other nostril. 7. Wipe the nasal applicator with a clean tissue and replace the plastic cap. Each bottle of mometasone furoate nasal spray contains enough medicine for you to spray medicine from the bottle 120 times. Do not use the bottle of mometasone furoate nasal spray after 120 sprays.

h the mouth. 6. Repeat in the other nostril. 7. Wipe the nasal applicator with a clean tissue and replace the plastic cap. Each bottle of mometasone furoate nasal spray contains enough medicine for you to spray medicine from the bottle 120 times. Do not use the bottle of mometasone furoate nasal spray after 120 sprays. Additional sprays after the 120 sprays may not contain the right amount of medicine, you should keep track of the number of sprays used from each bottle of mometasone furoate nasal spray, and throw away the bottle even if it has medicine still left in. Do not count any sprays used for priming the device. Talk with your healthcare provider before your supply runs out to see if you should get a refill of your medicine. Pediatric Use: Administration to children should be supervised by an adult. Steps 1 through 7 from the Patient Instructions for Use should be followed. Cleaning: Do not try to unblock the nasal applicator with a sharp object. Please see Patient Instructions for Cleaning Applicator . Patient Instructions for Cleaning Applicator 1. To clean the nasal applicator, remove the plastic cap ( See Figure 5). 2. Pull gently upward on the white nasal applicator to remove ( See Figure 6). 3. Soak the nasal applicator in cold tap water and rinse both ends of the nasal applicator under cold tap water and dry ( See Figure 7). Do not try to unblock the nasal applicator by inserting a pin or other sharp object as this will damage the applicator and cause you not to get the right dose of medicine. 4. Rinse the plastic cap under cold water and dry ( See Figure 8). 5. Put the nasal applicator back together making sure the pump stem is reinserted into the applicator's center hole ( See Figure 9). 6. Reprime the pump by pressing downward on the shoulders of the white nasal applicator using your index and middle fingers while holding the base of the bottle with your thumb. Press down and release the pump 2 times or until a fine spray appears. Do Not spray into eyes. The pump is now ready to use. The pump may be stored unused for up to 1 week without repriming. If unused for more than 1 week, reprime by spraying 2 times or until a fine spray appears ( See Figure 10). 7. Replace the plastic cap ( See Figure 11). This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration. APOTEX INC. MOMETASONE FUROATE NASAL SPRAY 50 mcg Manufactured by: Manufactured for: Apotex Inc. Apotex Corp. Toronto, Ontario Weston, FL M9L 1T9 33326 Revised: March 2025 figure1 figure2 figure3 figure4 figure5 figure6 figure7 figure9 figure10 figure11

<table><tbody><tr><td><content styleCode="bold">Manufactured by:</content></td><td><content styleCode="bold">Manufactured for:</content><content styleCode="bold"> </content></td></tr><tr><td> Apotex Inc. Toronto, Ontario M9L 1T9<content styleCode="bold"/></td><td> Apotex Corp. Weston, FL 33326<content styleCode="bold"/></td></tr></tbody></table> <table border="null" frame="void" rules="groups"><tbody align="left"><tr><th colspan="1" rowspan="1">Manufactured by:</th><th colspan="50" rowspan="1"/><th colspan="1" rowspan="1">Manufactured for:</th></tr><tr><th colspan="1" rowspan="1">Apotex Inc.</th><th colspan="50" rowspan="1"/><th colspan="1" rowspan="1">Apotex Corp.</th></tr><tr><th colspan="1" rowspan="1">Toronto, Ontario</th><th colspan="50" rowspan="1"/><th colspan="1" rowspan="1">Weston, FL</th></tr><tr><th colspan="1" rowspan="1">M9L 1T9</th><th colspan="50" rowspan="1"/><th colspan="1" rowspan="1">33326</th></tr></tbody></table>