MOMETASONE FUROATE MONOHYDRATE

Mometasone furoate monohydrate, the active component of Mometasone Furoate Monohydrate 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) monohydrate, and the following chemical structure: Mometasone furoate monohydrate is a white to off-white powder, with a molecular formula of C 27 H 30 Cl 2 O 6 •H 2 O, and a molecular weight of 539.45. It is practically insoluble in water; slightly soluble in methanol, ethanol, and isopropanol; soluble in acetone and chloroform; and freely soluble in tetrahydrofuran. Its partition coefficient between octanol and water is greater than 5000. Mometasone Furoate Monohydrate Nasal Spray is a metered-dose, manual pump spray. After initial priming (10 actuations), each actuation of the pump delivers a metered spray containing 100 mg or 100 microliter of aqueous suspension of mometasone furoate monohydrate equivalent to 50 mcg (0.05% w/w) mometasone furoate calculated on the anhydrous basis; in an aqueous medium containing benzalkonium chloride, citric acid monohydrate, glycerin, microcrystalline cellulose and carboxymethylcellulose sodium, polysorbate 80, purified water and sodium citrate (dihydrate). The pH is between 4.3 and 4.9. structure

Mometasone Furoate Monohydrate 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 monohydrate 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 monohydrate nasal spray is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients 18 years of age and older.

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 years 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 monohydrate nasal spray by the nasal route only. Initial Priming Prior to initial use of mometasone furoate monohydrate 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 monohydrate 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 monohydrate 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.

Mometasone furoate monohydrate 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 monohydrate nasal spray. ( 4 )

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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 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 3210 adult and pediatric patients 12 years and older with allergic rhinitis received treatment with mometasone furoate monohydrate nasal spray at doses of 50 to 800 mcg/day. The majority of patients (n=2103) 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 monohydrate nasal spray, 200 mcg/day vs. placebo and that were more common with mometasone furoate monohydrate 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 Monohydrate Nasal Spray 200 mcg (n=2103) % VEHICLE PLACEBO (n=1671) % 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 monohydrate 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. A total of 594 adult patients (ages 18 to 86 years) received mometasone furoate monohydrate 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 monohydrate 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 monohydrate 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 monohydrate 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.

No formal drug-drug interaction studies have been conducted with mometasone furoate monohydrate 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 monohydrate 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.