MOMETASONE FUROATE

Indications and Usage ( 1 ) (removed) 06/2022 Dosage and Administration ( 2 ) (removed) 06/2022

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 50 mcg 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 50 mcg is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients 18 years of age and older.

Purpose Allergy symptom reliever

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.

3 DOSAGE FORMS AND STRENGTHS Nasal spray: 50 mcg of mometasone furoate in each spray. Nasal spray: 50 mcg of mometasone furoate, USP in each spray (3)

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 )

Do not use ■ in children under 2 years of age ■ to treat asthma ■ if you have an injury or surgery to your nose that is not fully healed ■ if you have ever had an allergic reaction to this product or any of the ingredients

Ask a doctor before use if you ■ have an eye infection ■ have or had glaucoma or cataracts

Stop use and ask a doctor if ■ you have, or come into contact with someone who has chickenpox, measles or tuberculosis ■ your symptoms do not get better within 7 days of starting use or you get new symptoms such as severe facial pain or thick nasal discharge. You may have something more than allergies, such as an infection. ■ you get a constant whistling sound from your nose. This may be a sign of damage inside your nose. ■ you get an allergic reaction to this product. Seek medical help right away. ■ you get new changes to your vision that develop after starting this product ■ you have severe or frequent nose bleeds

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. 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 reactio …

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 co-administration 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 co-administration 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). 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 spra …

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).

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

Active ingredient (in each spray) Mometasone furoate monohydrate (glucocorticoid) 50 mcg

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 ) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Mometasone furoate nasal spray, 50 mcg is supplied in a white, high-density, polyethylene bottle fitted with a white metered-dose, manual spray pump, and turquoise cap. It contains 17 g of product formulation, 120 sprays, each delivering 50 mcg of mometasone furoate, USP per actuation. NDC 65162-891-29 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. When mometasone furoate nasal spray, 50 mcg 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. Keep out of reach of children.